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‘A few mutations away’: The threat of a vaccine-proof variant
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
The Centers for Disease Control and Prevention Director Rochelle Walensky, MD, MPH, made a dire prediction during a media briefing this week that, if we weren’t already living within the reality of the COVID-19 pandemic, would sound more like a pitch for a movie about a dystopian future.
“For the amount of virus circulating in this country right now largely among unvaccinated people, the largest concern that we in public health and science are worried about is that the virus … [becomes] a very transmissible virus that has the potential to evade our vaccines in terms of how it protects us from severe disease and death,” Dr. Walensky told reporters on July 27.
A new, more elusive variant could be “just a few mutations away,” she said.
“That’s a very prescient comment,” Lewis Nelson, MD, professor and clinical chair of emergency medicine and chief of the division of medical toxicology at Rutgers New Jersey Medical School in Newark, told this news organization.
“We’ve gone through a few mutations already that have been named, and each one of them gets a little more transmissible,” he said. “That’s normal, natural selection and what you would expect to happen as viruses mutate from one strain to another.”
“What we’ve mostly seen this virus do is evolve to become more infectious,” said Stuart Ray, MD, when also asked to comment. “That is the remarkable feature of Delta – that it is so infectious.”
He said that the SARS-CoV-2 has evolved largely as expected, at least so far. “The potential for this virus to mutate has been something that has been a concern from early on.”
“The viral evolution is a bit like a ticking clock. The more we allow infections to occur, the more likely changes will occur. When we have lots of people infected, we give more chances to the virus to diversify and then adapt to selective pressures,” said Dr. Ray, vice-chair of medicine for data integrity and analytics and professor in the division of infectious diseases at Johns Hopkins School of Medicine in Baltimore.
Dr. Nelson said.
If this occurs, he added, “we will have an ineffective vaccine, essentially. And we’ll be back to where we were last March with a brand-new disease.”
Technology to the rescue?
The flexibility of mRNA vaccines is one potential solution. These vaccines could be more easily and quickly adapted to respond to a new, more vaccine-elusive variant.
“That’s absolutely reassuring,” Dr. Nelson said. For example, if a mutation changes the spike protein and vaccines no longer recognize it, a manufacturer could identify the new protein and incorporate that in a new mRNA vaccine.
“The problem is that some people are not taking the current vaccine,” he added. “I’m not sure what is going to make them take the next vaccine.”
Nothing appears certain
When asked how likely a new strain of SARS-CoV-2 could emerge that gets around vaccine protection, Dr. Nelson said, “I think [what] we’ve learned so far there is no way to predict anything” about this pandemic.
“The best way to prevent the virus from mutating is to prevent hosts, people, from getting sick with it,” he said. “That’s why it’s so important people should get immunized and wear masks.”
Both Dr. Nelson and Dr. Ray pointed out that it is in the best interest of the virus to evolve to be more transmissible and spread to more people. In contrast, a virus that causes people to get so sick that they isolate or die, thus halting transmission, works against viruses surviving evolutionarily.
Some viruses also mutate to become milder over time, but that has not been the case with SARS-CoV-2, Dr. Ray said.
Mutations not the only concern
Viruses have another mechanism that produces new strains, and it works even more quickly than mutations. Recombination, as it’s known, can occur when a person is infected with two different strains of the same virus. If the two versions enter the same cell, the viruses can swap genetic material and produce a third, altogether different strain.
Recombination has already been seen with influenza strains, where H and N genetic segments are swapped to yield H1N1, H1N2, and H3N2 versions of the flu, for example.
“In the early days of SARS-CoV-2 there was so little diversity that recombination did not matter,” Dr. Ray said. However, there are now distinct lineages of the virus circulating globally. If two of these lineages swap segments “this would make a very new viral sequence in one step without having to mutate to gain those differences.”
“The more diverse the strains that are circulating, the bigger a possibility this is,” Dr. Ray said.
Protected, for now
Dr. Walensky’s sober warning came at the same time the CDC released new guidance calling for the wearing of masks indoors in schools and in any location in the country where COVID-19 cases surpass 50 people per 100,000, also known as substantial or high transmission areas.
On a positive note, Dr. Walensky said: “Right now, fortunately, we are not there. The vaccines operate really well in protecting us from severe disease and death.”
A version of this article first appeared on Medscape.com.
FDA approves first interchangeable biosimilar insulin
The
The approval will allow Semglee to function like a generic drug in the market and may reduce insulin costs.
It is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.
Originally approved in June 2020 as a biosimilar to glargine, Semglee is now an “interchangeable biosimilar,” meaning that it has no clinically meaningful difference from the reference product and also may be substituted for that product – in this case, glargine (Lantus) – without prescriber intervention, just as generic drugs typically are, subject to state pharmacy laws.
For approval as an interchangeable biosimilar, manufacturers are required to provide additional data reflecting how the interchangeable biosimilar may be used in the marketplace with patients.
“Biosimilar and interchangeable biosimilar products have the potential to reduce health care costs, similar to how generic drugs have reduced costs. Biosimilars marketed in the U.S. typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products,” the FDA said in a statement.
Semglee comes in 10-mL and 3-mL prefilled pens, and is administered subcutaneously once daily, with individualized doses. The most common side effects are hypoglycemia, edema, lipodystrophy, weight gain, and allergic reactions.
The FDA released new materials for health care providers regarding biosimilar and interchangeable biosimilar products, including a fact sheet about interchangeable biosimilar products.
A version of this article first appeared on Medscape.com.
The
The approval will allow Semglee to function like a generic drug in the market and may reduce insulin costs.
It is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.
Originally approved in June 2020 as a biosimilar to glargine, Semglee is now an “interchangeable biosimilar,” meaning that it has no clinically meaningful difference from the reference product and also may be substituted for that product – in this case, glargine (Lantus) – without prescriber intervention, just as generic drugs typically are, subject to state pharmacy laws.
For approval as an interchangeable biosimilar, manufacturers are required to provide additional data reflecting how the interchangeable biosimilar may be used in the marketplace with patients.
“Biosimilar and interchangeable biosimilar products have the potential to reduce health care costs, similar to how generic drugs have reduced costs. Biosimilars marketed in the U.S. typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products,” the FDA said in a statement.
Semglee comes in 10-mL and 3-mL prefilled pens, and is administered subcutaneously once daily, with individualized doses. The most common side effects are hypoglycemia, edema, lipodystrophy, weight gain, and allergic reactions.
The FDA released new materials for health care providers regarding biosimilar and interchangeable biosimilar products, including a fact sheet about interchangeable biosimilar products.
A version of this article first appeared on Medscape.com.
The
The approval will allow Semglee to function like a generic drug in the market and may reduce insulin costs.
It is indicated to improve glycemic control in adults and pediatric patients with type 1 diabetes and in adults with type 2 diabetes.
Originally approved in June 2020 as a biosimilar to glargine, Semglee is now an “interchangeable biosimilar,” meaning that it has no clinically meaningful difference from the reference product and also may be substituted for that product – in this case, glargine (Lantus) – without prescriber intervention, just as generic drugs typically are, subject to state pharmacy laws.
For approval as an interchangeable biosimilar, manufacturers are required to provide additional data reflecting how the interchangeable biosimilar may be used in the marketplace with patients.
“Biosimilar and interchangeable biosimilar products have the potential to reduce health care costs, similar to how generic drugs have reduced costs. Biosimilars marketed in the U.S. typically have launched with initial list prices 15% to 35% lower than comparative list prices of the reference products,” the FDA said in a statement.
Semglee comes in 10-mL and 3-mL prefilled pens, and is administered subcutaneously once daily, with individualized doses. The most common side effects are hypoglycemia, edema, lipodystrophy, weight gain, and allergic reactions.
The FDA released new materials for health care providers regarding biosimilar and interchangeable biosimilar products, including a fact sheet about interchangeable biosimilar products.
A version of this article first appeared on Medscape.com.
FDA warns of higher death risk with Pepaxto in multiple myeloma
participating in the ongoing OCEAN clinical trial.
The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.
Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.
The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.
Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”
The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
Accelerated approval data
Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.
The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.
Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
Confirmatory trial data
The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.
The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.
“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.
The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.
Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.
A version of this article first appeared on Medscape.com.
participating in the ongoing OCEAN clinical trial.
The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.
Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.
The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.
Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”
The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
Accelerated approval data
Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.
The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.
Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
Confirmatory trial data
The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.
The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.
“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.
The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.
Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.
A version of this article first appeared on Medscape.com.
participating in the ongoing OCEAN clinical trial.
The drug was granted accelerated approval in February 2021 for use in combination with dexamethasone in the treatment of adults with relapsed or refractory multiple myeloma who had received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
As a condition of the accelerated approval, the manufacturer, Oncopeptides, was required to conduct a confirmatory clinical trial and launched the OCEAN trial.
Enrollment in OCEAN as well as other ongoing trials of the drug have now been halted, according to the FDA alert.
The warning comes in the wake of OCEAN trial findings showing worse survival among patients in the experimental group, who were receiving melphalan plus low-dose dexamethasone, compared with patients in the control group, who were receiving pomalidomide plus low-dose dexamethasone (hazard ratio for overall survival, 1.104). Median overall survival in the treatment and control groups was 19.7 and 25.0 months, respectively.
Health care professionals should “review patients’ progress on Pepaxto and discuss the risks of continued administration with each patient in the context of other treatments,” and patients currently receiving the drug should discuss the risks and benefits with their health care professional, the FDA advises. “Patients receiving clinical benefit from Pepaxto may continue treatment in the OCEAN trial provided they are informed of the risks and sign a revised written informed consent.”
The FDA also hinted at “a future public meeting to discuss the safety findings and explore the continued marketing of Pepaxto,” which has a price tag of $19,000 per treatment course.
Accelerated approval data
Melphalan flufenamide was initially evaluated in combination with low-dose dexamethasone in the multicenter, single-arm HORIZON trial of adults with relapsed or refractory multiple myeloma who received at least four prior lines of therapy and whose disease was refractory to at least one proteasome inhibitor, one immunomodulator, and one CD38-directed monoclonal antibody.
Patients received melphalan flufenamide at a dose of 40 mg intravenously on day 1 along with oral dexamethasone at a dose of 40 mg (or 20 mg for those over age 75 years) on days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.
The most common adverse reactions, occurring in at least 20% of patients, were fatigue, nausea, diarrhea, pyrexia, and respiratory tract infection. The most common laboratory abnormalities, occurring in at least 50% of patients, were decreased leukocytes, platelets, lymphocytes, neutrophils, and hemoglobin, and increased creatinine.
Accelerated approval was granted after the HORIZON trial showed an overall response rate of 23.7% and median duration of response of 4.2 months. The application by Oncopeptides received priority review and orphan drug status.
Confirmatory trial data
The confirmatory OCEAN trial compared melphalan flufenamide plus low-dose dexamethasone to pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma following 2-4 lines of therapy and in patients who were resistant to lenalidomide in the last line of therapy.
The FDA conducted an efficacy and safety evaluation of the OCEAN trial using a data cutoff date of February 3, 2021. At a median follow-up of 19.1 months, 117 of 246 patients (48%) in the melphalan flufenamide group had died, compared with 108 of 249 patients (43%) in the pomalidomide control group.
“Patient safety is paramount to Oncopeptides,” the company said in a press statement, which also notes that “dialogue with the FDA” is ongoing and that updated information will be provided as it becomes available.
The company plans to submit complete data from the OCEAN study to the International Myeloma Workshop meeting in Vienna being held September 8-11, 2021.
Health care professionals and patients should report adverse events or quality issues experienced with melphalan flufenamide or any other medication to the FDA MedWatch Adverse Event Reporting program, either online or by downloading and completing a reporting form and submitting via fax at 1-800-FDA-0178.
A version of this article first appeared on Medscape.com.
CDC calls for masks in schools, hard-hit areas, even if vaccinated
The agency has called for masks in K-12 school settings and in areas of the United States experiencing high or substantial SARS-CoV-2 transmission, even for the fully vaccinated.
The move reverses a controversial announcement the agency made in May 2021 that fully vaccinated Americans could skip wearing a mask in most settings.
Unlike the increasing vaccination rates and decreasing case numbers reported in May, however, some regions of the United States are now reporting large jumps in COVID-19 case numbers. And the Delta variant as well as new evidence of transmission from breakthrough cases are largely driving these changes.
“Today we have new science related to the [D]elta variant that requires us to update the guidance on what you can do when you are fully vaccinated,” CDC Director Rochelle Walensky, MD, MPH, said during a media briefing July 27.
New evidence has emerged on breakthrough-case transmission risk, for example. “Information on the [D]elta variant from several states and other countries indicates that in rare cases, some people infected with the [D]elta variant after vaccination may be contagious and spread virus to others,” Dr. Walensky said, adding that the viral loads appear to be about the same in vaccinated and unvaccinated individuals.
“This new science is worrisome,” she said.
Even though unvaccinated people represent the vast majority of cases of transmission, Dr. Walensky said, “we thought it was important for [vaccinated] people to understand they have the potential to transmit the virus to others.”
As a result, in addition to continuing to strongly encourage everyone to get vaccinated, the CDC recommends that fully vaccinated people wear masks in public indoor settings to help prevent the spread of the Delta variant in areas with substantial or high transmission, Dr. Walensky said. “This includes schools.”
Masks in schools
The CDC is now recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status. Their goal is to optimize safety and allow children to return to full-time in-person learning in the fall.
The CDC tracks substantial and high transmission rates through the agency’s COVID Data Tracker site. Substantial transmission means between 50 and 100 cases per 100,000 people reported over 7 days and high means more than 100 cases per 100,000 people.
The B.1.617.2, or Delta, variant is believed to be responsible for COVID-19 cases increasing more than 300% nationally from June 19 to July 23, 2021.
“A prudent move”
“I think it’s a prudent move. Given the dominance of the [D]elta variant and the caseloads that we are seeing rising in many locations across the United States, including in my backyard here in San Francisco,” Joe DeRisi, PhD, copresident of the Chan Zuckerberg Biohub and professor of biochemistry and biophysics at the University of California San Francisco, said in an interview.
Dr. DeRisi said he was not surprised that vaccinated people with breakthrough infections could be capable of transmitting the virus. He added that clinical testing done by the Biohub and UCSF produced a lot of data on viral load levels, “and they cover an enormous range.”
What was unexpected to him was the rapid rise of the dominant variant. “The rise of the [D]elta strain is astonishing. It’s happened so fast,” he said.
“I know it’s difficult”
Reacting to the news, Colleen Kraft, MD, said, “One of the things that we’re learning is that if we’re going to have low vaccine uptake or we have a number of people that can’t be vaccinated yet, such as children, that we really need to go back to stopping transmission, which involves mask wearing.”
“I know that it’s very difficult and people feel like we’re sliding backward,” Dr. Kraft said during a media briefing sponsored by Emory University held shortly after the CDC announcement.
She added that the CDC updated guidance seems appropriate. “I don’t think any of us really want to be in this position or want to go back to masking but…we’re finding ourselves in the same place we were a year ago, in July 2020.
“In general we just don’t want anybody to be infected even if there’s a small chance for you to be infected and there’s a small chance for you to transmit it,” said Dr. Kraft, who’s an assistant professor in the department of pathology and associate professor in the department of medicine, division of infectious diseases at Emory University School of Medicine in Atlanta.
Breakthrough transmissions
“The good news is you’re still unlikely to get critically ill if you’re vaccinated. But what has changed with the [D]elta variant is instead of being 90% plus protected from getting the virus at all, you’re probably more in the 70% to 80% range,” James T. McDeavitt, MD, told this news organization.
“So we’re seeing breakthrough infections,” said Dr. McDeavitt, executive vice president and dean of clinical affairs at Baylor College of Medicine in Houston. “We are starting to see [such people] are potentially infectious.” Even if a vaccinated person is individually much less likely to experience serious COVID-19 outcomes, “they can spread it to someone else who spreads it to someone else who is more vulnerable. It puts the more at-risk populations at further risk.”
It breaks down to individual and public health concerns. “I am fully vaccinated. I am very confident I am not going to end up in a hospital,” he said. “Now if I were unvaccinated, with the prevalence of the virus around the country, I’m probably in more danger than I’ve ever been in the course of the pandemic. The unvaccinated are really at risk right now.”
IDSA and AMA support mask change
The Infectious Diseases Society of America (IDSA) has released a statement supporting the new CDC recommendations. “To stay ahead of the spread of the highly transmissible Delta variant, IDSA also urges that in communities with moderate transmission rates, all individuals, even those who are vaccinated, wear masks in indoor public places,” stated IDSA President Barbara D. Alexander, MD, MHS.
“IDSA also supports CDC’s guidance recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status, until vaccines are authorized and widely available to all children and vaccination rates are sufficient to control transmission.”
“Mask wearing will help reduce infections, prevent serious illnesses and death, limit strain on local hospitals and stave off the development of even more troubling variants,” she added.
The American Medical Association (AMA) also released a statement supporting the CDC’s policy changes.
“According to the CDC, emerging data indicates that vaccinated individuals infected with the Delta variant have similar viral loads as those who are unvaccinated and are capable of transmission,” AMA President Gerald E. Harmon, MD said in the statement.
“However, the science remains clear, the authorized vaccines remain safe and effective in preventing severe complications from COVID-19, including hospitalization and death,” he stated. “We strongly support the updated recommendations, which call for universal masking in areas of high or substantial COVID-19 transmission and in K-12 schools, to help reduce transmission of the virus. Wearing a mask is a small but important protective measure that can help us all stay safer.”
“The highest spread of cases and [most] severe outcomes are happening in places with low vaccination rates and among unvaccinated people,” Dr. Walensky said. “With the [D]elta variant, vaccinating more Americans now is more urgent than ever.”
“This moment, and the associated suffering, illness, and death, could have been avoided with higher vaccination coverage in this country,” she said.
A version of this article first appeared on Medscape.com.
The agency has called for masks in K-12 school settings and in areas of the United States experiencing high or substantial SARS-CoV-2 transmission, even for the fully vaccinated.
The move reverses a controversial announcement the agency made in May 2021 that fully vaccinated Americans could skip wearing a mask in most settings.
Unlike the increasing vaccination rates and decreasing case numbers reported in May, however, some regions of the United States are now reporting large jumps in COVID-19 case numbers. And the Delta variant as well as new evidence of transmission from breakthrough cases are largely driving these changes.
“Today we have new science related to the [D]elta variant that requires us to update the guidance on what you can do when you are fully vaccinated,” CDC Director Rochelle Walensky, MD, MPH, said during a media briefing July 27.
New evidence has emerged on breakthrough-case transmission risk, for example. “Information on the [D]elta variant from several states and other countries indicates that in rare cases, some people infected with the [D]elta variant after vaccination may be contagious and spread virus to others,” Dr. Walensky said, adding that the viral loads appear to be about the same in vaccinated and unvaccinated individuals.
“This new science is worrisome,” she said.
Even though unvaccinated people represent the vast majority of cases of transmission, Dr. Walensky said, “we thought it was important for [vaccinated] people to understand they have the potential to transmit the virus to others.”
As a result, in addition to continuing to strongly encourage everyone to get vaccinated, the CDC recommends that fully vaccinated people wear masks in public indoor settings to help prevent the spread of the Delta variant in areas with substantial or high transmission, Dr. Walensky said. “This includes schools.”
Masks in schools
The CDC is now recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status. Their goal is to optimize safety and allow children to return to full-time in-person learning in the fall.
The CDC tracks substantial and high transmission rates through the agency’s COVID Data Tracker site. Substantial transmission means between 50 and 100 cases per 100,000 people reported over 7 days and high means more than 100 cases per 100,000 people.
The B.1.617.2, or Delta, variant is believed to be responsible for COVID-19 cases increasing more than 300% nationally from June 19 to July 23, 2021.
“A prudent move”
“I think it’s a prudent move. Given the dominance of the [D]elta variant and the caseloads that we are seeing rising in many locations across the United States, including in my backyard here in San Francisco,” Joe DeRisi, PhD, copresident of the Chan Zuckerberg Biohub and professor of biochemistry and biophysics at the University of California San Francisco, said in an interview.
Dr. DeRisi said he was not surprised that vaccinated people with breakthrough infections could be capable of transmitting the virus. He added that clinical testing done by the Biohub and UCSF produced a lot of data on viral load levels, “and they cover an enormous range.”
What was unexpected to him was the rapid rise of the dominant variant. “The rise of the [D]elta strain is astonishing. It’s happened so fast,” he said.
“I know it’s difficult”
Reacting to the news, Colleen Kraft, MD, said, “One of the things that we’re learning is that if we’re going to have low vaccine uptake or we have a number of people that can’t be vaccinated yet, such as children, that we really need to go back to stopping transmission, which involves mask wearing.”
“I know that it’s very difficult and people feel like we’re sliding backward,” Dr. Kraft said during a media briefing sponsored by Emory University held shortly after the CDC announcement.
She added that the CDC updated guidance seems appropriate. “I don’t think any of us really want to be in this position or want to go back to masking but…we’re finding ourselves in the same place we were a year ago, in July 2020.
“In general we just don’t want anybody to be infected even if there’s a small chance for you to be infected and there’s a small chance for you to transmit it,” said Dr. Kraft, who’s an assistant professor in the department of pathology and associate professor in the department of medicine, division of infectious diseases at Emory University School of Medicine in Atlanta.
Breakthrough transmissions
“The good news is you’re still unlikely to get critically ill if you’re vaccinated. But what has changed with the [D]elta variant is instead of being 90% plus protected from getting the virus at all, you’re probably more in the 70% to 80% range,” James T. McDeavitt, MD, told this news organization.
“So we’re seeing breakthrough infections,” said Dr. McDeavitt, executive vice president and dean of clinical affairs at Baylor College of Medicine in Houston. “We are starting to see [such people] are potentially infectious.” Even if a vaccinated person is individually much less likely to experience serious COVID-19 outcomes, “they can spread it to someone else who spreads it to someone else who is more vulnerable. It puts the more at-risk populations at further risk.”
It breaks down to individual and public health concerns. “I am fully vaccinated. I am very confident I am not going to end up in a hospital,” he said. “Now if I were unvaccinated, with the prevalence of the virus around the country, I’m probably in more danger than I’ve ever been in the course of the pandemic. The unvaccinated are really at risk right now.”
IDSA and AMA support mask change
The Infectious Diseases Society of America (IDSA) has released a statement supporting the new CDC recommendations. “To stay ahead of the spread of the highly transmissible Delta variant, IDSA also urges that in communities with moderate transmission rates, all individuals, even those who are vaccinated, wear masks in indoor public places,” stated IDSA President Barbara D. Alexander, MD, MHS.
“IDSA also supports CDC’s guidance recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status, until vaccines are authorized and widely available to all children and vaccination rates are sufficient to control transmission.”
“Mask wearing will help reduce infections, prevent serious illnesses and death, limit strain on local hospitals and stave off the development of even more troubling variants,” she added.
The American Medical Association (AMA) also released a statement supporting the CDC’s policy changes.
“According to the CDC, emerging data indicates that vaccinated individuals infected with the Delta variant have similar viral loads as those who are unvaccinated and are capable of transmission,” AMA President Gerald E. Harmon, MD said in the statement.
“However, the science remains clear, the authorized vaccines remain safe and effective in preventing severe complications from COVID-19, including hospitalization and death,” he stated. “We strongly support the updated recommendations, which call for universal masking in areas of high or substantial COVID-19 transmission and in K-12 schools, to help reduce transmission of the virus. Wearing a mask is a small but important protective measure that can help us all stay safer.”
“The highest spread of cases and [most] severe outcomes are happening in places with low vaccination rates and among unvaccinated people,” Dr. Walensky said. “With the [D]elta variant, vaccinating more Americans now is more urgent than ever.”
“This moment, and the associated suffering, illness, and death, could have been avoided with higher vaccination coverage in this country,” she said.
A version of this article first appeared on Medscape.com.
The agency has called for masks in K-12 school settings and in areas of the United States experiencing high or substantial SARS-CoV-2 transmission, even for the fully vaccinated.
The move reverses a controversial announcement the agency made in May 2021 that fully vaccinated Americans could skip wearing a mask in most settings.
Unlike the increasing vaccination rates and decreasing case numbers reported in May, however, some regions of the United States are now reporting large jumps in COVID-19 case numbers. And the Delta variant as well as new evidence of transmission from breakthrough cases are largely driving these changes.
“Today we have new science related to the [D]elta variant that requires us to update the guidance on what you can do when you are fully vaccinated,” CDC Director Rochelle Walensky, MD, MPH, said during a media briefing July 27.
New evidence has emerged on breakthrough-case transmission risk, for example. “Information on the [D]elta variant from several states and other countries indicates that in rare cases, some people infected with the [D]elta variant after vaccination may be contagious and spread virus to others,” Dr. Walensky said, adding that the viral loads appear to be about the same in vaccinated and unvaccinated individuals.
“This new science is worrisome,” she said.
Even though unvaccinated people represent the vast majority of cases of transmission, Dr. Walensky said, “we thought it was important for [vaccinated] people to understand they have the potential to transmit the virus to others.”
As a result, in addition to continuing to strongly encourage everyone to get vaccinated, the CDC recommends that fully vaccinated people wear masks in public indoor settings to help prevent the spread of the Delta variant in areas with substantial or high transmission, Dr. Walensky said. “This includes schools.”
Masks in schools
The CDC is now recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status. Their goal is to optimize safety and allow children to return to full-time in-person learning in the fall.
The CDC tracks substantial and high transmission rates through the agency’s COVID Data Tracker site. Substantial transmission means between 50 and 100 cases per 100,000 people reported over 7 days and high means more than 100 cases per 100,000 people.
The B.1.617.2, or Delta, variant is believed to be responsible for COVID-19 cases increasing more than 300% nationally from June 19 to July 23, 2021.
“A prudent move”
“I think it’s a prudent move. Given the dominance of the [D]elta variant and the caseloads that we are seeing rising in many locations across the United States, including in my backyard here in San Francisco,” Joe DeRisi, PhD, copresident of the Chan Zuckerberg Biohub and professor of biochemistry and biophysics at the University of California San Francisco, said in an interview.
Dr. DeRisi said he was not surprised that vaccinated people with breakthrough infections could be capable of transmitting the virus. He added that clinical testing done by the Biohub and UCSF produced a lot of data on viral load levels, “and they cover an enormous range.”
What was unexpected to him was the rapid rise of the dominant variant. “The rise of the [D]elta strain is astonishing. It’s happened so fast,” he said.
“I know it’s difficult”
Reacting to the news, Colleen Kraft, MD, said, “One of the things that we’re learning is that if we’re going to have low vaccine uptake or we have a number of people that can’t be vaccinated yet, such as children, that we really need to go back to stopping transmission, which involves mask wearing.”
“I know that it’s very difficult and people feel like we’re sliding backward,” Dr. Kraft said during a media briefing sponsored by Emory University held shortly after the CDC announcement.
She added that the CDC updated guidance seems appropriate. “I don’t think any of us really want to be in this position or want to go back to masking but…we’re finding ourselves in the same place we were a year ago, in July 2020.
“In general we just don’t want anybody to be infected even if there’s a small chance for you to be infected and there’s a small chance for you to transmit it,” said Dr. Kraft, who’s an assistant professor in the department of pathology and associate professor in the department of medicine, division of infectious diseases at Emory University School of Medicine in Atlanta.
Breakthrough transmissions
“The good news is you’re still unlikely to get critically ill if you’re vaccinated. But what has changed with the [D]elta variant is instead of being 90% plus protected from getting the virus at all, you’re probably more in the 70% to 80% range,” James T. McDeavitt, MD, told this news organization.
“So we’re seeing breakthrough infections,” said Dr. McDeavitt, executive vice president and dean of clinical affairs at Baylor College of Medicine in Houston. “We are starting to see [such people] are potentially infectious.” Even if a vaccinated person is individually much less likely to experience serious COVID-19 outcomes, “they can spread it to someone else who spreads it to someone else who is more vulnerable. It puts the more at-risk populations at further risk.”
It breaks down to individual and public health concerns. “I am fully vaccinated. I am very confident I am not going to end up in a hospital,” he said. “Now if I were unvaccinated, with the prevalence of the virus around the country, I’m probably in more danger than I’ve ever been in the course of the pandemic. The unvaccinated are really at risk right now.”
IDSA and AMA support mask change
The Infectious Diseases Society of America (IDSA) has released a statement supporting the new CDC recommendations. “To stay ahead of the spread of the highly transmissible Delta variant, IDSA also urges that in communities with moderate transmission rates, all individuals, even those who are vaccinated, wear masks in indoor public places,” stated IDSA President Barbara D. Alexander, MD, MHS.
“IDSA also supports CDC’s guidance recommending universal indoor masking for all teachers, staff, students, and visitors to K-12 schools, regardless of vaccination status, until vaccines are authorized and widely available to all children and vaccination rates are sufficient to control transmission.”
“Mask wearing will help reduce infections, prevent serious illnesses and death, limit strain on local hospitals and stave off the development of even more troubling variants,” she added.
The American Medical Association (AMA) also released a statement supporting the CDC’s policy changes.
“According to the CDC, emerging data indicates that vaccinated individuals infected with the Delta variant have similar viral loads as those who are unvaccinated and are capable of transmission,” AMA President Gerald E. Harmon, MD said in the statement.
“However, the science remains clear, the authorized vaccines remain safe and effective in preventing severe complications from COVID-19, including hospitalization and death,” he stated. “We strongly support the updated recommendations, which call for universal masking in areas of high or substantial COVID-19 transmission and in K-12 schools, to help reduce transmission of the virus. Wearing a mask is a small but important protective measure that can help us all stay safer.”
“The highest spread of cases and [most] severe outcomes are happening in places with low vaccination rates and among unvaccinated people,” Dr. Walensky said. “With the [D]elta variant, vaccinating more Americans now is more urgent than ever.”
“This moment, and the associated suffering, illness, and death, could have been avoided with higher vaccination coverage in this country,” she said.
A version of this article first appeared on Medscape.com.
FDA okays extended-release exenatide for children with T2D
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
the agency announced July 22.
Previously approved in adults, the injectable is now the second glucagonlike peptide-1 receptor agonist approved for use in pediatric type 2 diabetes, after liraglutide (Victoza, Novo Nordisk) in 2019, and the first with once-weekly administration.
The two extended-release Bydureon products – which differ in delivery device and mixing procedure – are now indicated for use in addition to diet and exercise to improve glycemic control in pediatric patients 10 years of age or older with type 2 diabetes.
Exenatide extended release is not recommended as first-line treatment following diet and exercise.
The approval was based on a 24-week, double-blind, placebo-controlled study in 82 children with type 2 diabetes aged 10 and older. They were randomized to 2 mg once-weekly exenatide extended release or placebo. At week 24, hemoglobin A1c in those randomized to the drug had dropped by 0.25 percentage points, compared with a 0.45 percentage point increase in the placebo group.
Side effects were similar to those seen in adults, including injection site reactions, headaches, and gastrointestinal discomfort.
Currently, metformin is the only oral medication approved for treating pediatric type 2 diabetes, while the injectables also include insulin in addition to the two GLP-1 receptor agonists. During a symposium held in June 2021 at the annual scientific sessions of the American Diabetes Association, speakers expressed alarm about the rise in youth developing type 2 diabetes, noting that the condition typically progresses more rapidly and is less likely to respond well to metformin, compared with adults.
But, the panelists were also optimistic about extended-release exenatide as well as several other therapies for pediatric patients with type 2 diabetes in ongoing phase 3 trials, including the sodium-glucose cotransporter 2 inhibitors dapagliflozin and empagliflozin, and the dipeptidyl peptidase–4 inhibitors alogliptin and linagliptin. Results are expected in the next 1-2 years.
CDC revamps STI treatment guidelines
On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.
The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.
Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”
Notable updates to the guidelines include the following:
- Updated treatment recommendations for gonorrhea, chlamydia, , and
- Two-step testing for diagnosing genital virus
- Expanded risk factors for testing in pregnant women
- Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
- A recommendation that universal screening be conducted at least once in a lifetime for adults aged 18 years and older
Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.
“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”
The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.
Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.
The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.
A version of this article first appeared on Medscape.com.
On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.
The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.
Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”
Notable updates to the guidelines include the following:
- Updated treatment recommendations for gonorrhea, chlamydia, , and
- Two-step testing for diagnosing genital virus
- Expanded risk factors for testing in pregnant women
- Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
- A recommendation that universal screening be conducted at least once in a lifetime for adults aged 18 years and older
Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.
“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”
The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.
Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.
The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.
A version of this article first appeared on Medscape.com.
On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.
The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.
Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”
Notable updates to the guidelines include the following:
- Updated treatment recommendations for gonorrhea, chlamydia, , and
- Two-step testing for diagnosing genital virus
- Expanded risk factors for testing in pregnant women
- Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
- A recommendation that universal screening be conducted at least once in a lifetime for adults aged 18 years and older
Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.
“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”
The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.
Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.
The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.
A version of this article first appeared on Medscape.com.
FDA OKs odevixibat for pruritus associated with rare liver disease
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration has approved odevixibat (Bylvay, Albireo Pharma), the first treatment for pruritus associated with all types of progressive familial intrahepatic cholestasis (PFIC).
PFIC is a rare disorder affecting an estimated one to two people per 100,000. The disorder usually appears within the first few months of life and causes progressive, life-threatening liver disease, often leading to cirrhosis and liver failure before age 10.
In PFIC, liver cells are unable to drain bile acids, leading to the buildup of toxic substances in the liver. While the precise cause of severe itching in patients with PFIC is unknown, it may involve increased levels of bile acids in the body and skin.
Odevixibat is a potent, nonsystemic ileal bile acid transport inhibitor that does not need refrigeration and is given as a once-daily capsule or opened and sprinkled onto soft foods, the company said in a news release announcing the approval.
There are at least three types of PFIC; all are inherited genetic conditions caused by gene mutations. Odevixibat is indicated to treat all subtypes.
“Treating children with PFIC can be difficult and frustrating given the current treatment options. Bylvay gives us a nonsurgical option and will change how we treat PFIC,” Richard Thompson, MD, principal investigator for the two trials that led to the approval, said in the news release.
“With this approval, my colleagues and I now have the opportunity to revisit how PFIC patients are being managed, and we are hopeful for better outcomes for these children,” said Dr. Thompson, professor of molecular hepatology at King’s College London.
The approval of odevixibat was supported by data from the PEDFIC 1 and PEDFIC 2 trials.
PEDFIC 1 enrolled 62 children with PFIC and severe itching, with 20 assigned to placebo and 42 to odevixibat, given once daily with a meal in the morning. Odevixibat met both of its primary endpoints, with the drug improving pruritus (P = .004) and reducing serum bile acid responses (P = .003).
In PEDFIC 2, a long-term, open-label extension study, the effects of odevixibat on pruritis and serum bile acids were sustained up to 48 weeks.
Odevixibat was well tolerated in both trials, with the most common treatment-related gastrointestinal adverse events being diarrhea/frequent stools. There were no serious treatment-related adverse events.
Children taking the drug should undergo liver test monitoring periodically during treatment, the FDA said when announcing the approval. Odevixibat may affect absorption of fat-soluble vitamins such as A, D, E, and K. Patients should be monitored for fat-soluble vitamin deficiency while taking the drug.
Full prescribing information is available online.
“Until now, invasive surgery was the only approved treatment option. With the approval of Bylvay, parents may find hope in having a less invasive treatment option available,” Emily Ventura, leader of the PFIC Advocacy and Resource Network and mother to a child with PFIC, said in the news release.
The company said it will launch odevixibat “immediately” to accelerate availability for patients and families affected by PFIC.
Odevixibat is also being studied in other rare pediatric cholestatic liver diseases, including biliary atresia and Alagille syndrome.
A version of this article first appeared on Medscape.com.
FDA OKs spinal cord stimulation for diabetic neuropathy pain
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
The Food and Drug Administration has approved the first high-frequency spinal cord stimulation (SCS) therapy for treating painful diabetic neuropathy (PDN).
The approval is specific for the treatment of chronic pain associated with PDN using the Nevro’s Senza System with 10 kHz stimulation. It is intended for patients whose pain is refractory to, or who can’t tolerate, conventional medical treatment. According to the company, there are currently about 2.3 million individuals with refractory PDN in the United States.
The 10 kHz device, called HFX, involves minimally invasive epidural implantation of the stimulator device, which delivers mild electrical impulses to the nerves to interrupt pain signal to the brain. Such spinal cord stimulation “is a straightforward, well-established treatment for chronic pain that’s been used for over 30 years,” according to the company, although this is the first approval of the modality specifically for PDN.
Asked to comment, Rodica Pop-Busui MD, PhD, the Larry D. Soderquist Professor in Diabetes at the University of Michigan, Ann Arbor, said that “the approval of the Nevro 10kHz high-frequency spinal cord stimulation to treat pain associated with diabetic neuropathy has the potential for benefit for many patients with diabetes and painful diabetic peripheral neuropathy.”
She noted that, “although there are several other pharmacological agents that currently carry the FDA approval for PDN, this is a condition that is notoriously difficult to treat, particularly when taking into account the actual number needed to treat with a specific agent to achieve a clinically meaningful pain reduction, as well as the spectrum of side effects and drug-drug interactions in a patient population that require many other additional agents to manage diabetes and comorbidities on a daily basis. Thus, this new therapeutic approach besides effective pain reduction has the additional benefit of bypassing drug interactions.” Dr. Pop-Busui was the lead author on the American Diabetes Association’s 2017 position statement on diabetic neuropathy.
She also cautioned, on the other hand, that “it is not very clear yet how easy it will be for all eligible patients to have access to this technology, what will be the actual costs, the insurance coverage, or the acceptance by patients across various sociodemographic backgrounds from the at-large clinical care. However, given the challenges we encounter to treat diabetic neuropathy and particularly the pain associated with it, it is quite encouraging to see that the tools available to help our patients are now broader.”
Both 6-and 12-month results show benefit
The FDA approval was based on 6-month data from a prospective, multicenter, open-label randomized clinical trial published in JAMA Neurology.
Use of the 10-kHz SCS device was compared with conventional treatment alone in 216 patients with PDN refractory to gabapentinoids and at least one other analgesic class and lower limb pain intensity of 5 cm or more on a 10-cm visual analog scale.
The primary endpoint, percentage of participants reporting 50% pain relief or more without worsening of baseline neurologic deficits at 3 months, was met by 5 of 94 (5%) patients in the conventional group, compared with 75 of 95 (79%) with the 10-kHz SCS plus conventional treatment (P < .001).
Infections requiring device explant occurred in two patients in the 10-kHz SCS group (2%).
At 12 months, those in the original SCS group plus 86% of subjects given the option to cross over from the conventional treatment group showed “clear and sustained” benefits of the 10-kHz SCS with regard to lower-limb pain, pain interference with daily living, sleep quality, and activity, Erika Petersen, MD, director of the section of functional and restorative neurosurgery at the University of Arkansas for Medical Sciences, Little Rock , reported at the 2021 annual scientific sessions of the ADA.
Infection was the most common study-related adverse event, affecting 8 of 154 patients with the SCS implants (5.2%). Three resolved with conservative treatment and five (3.2%) required removal of the device.
The patients will be followed for a total of 24 months.
Commercial launch of HFX in the United States will begin immediately, the company said.
Dr. Pop-Busui has received consultant fees in the last 12 months from Averitas Pharma, Boehringer Ingelheim, Nevro, and Novo Nordisk. Dr. Petersen has financial relationships with Nevro, Medtronic, and several other neuromodulator makers.
FDA approves intravenous immunoglobulin for dermatomyositis
, according to a statement from manufacturer Octapharma USA.
Dermatomyositis is a rare, idiopathic autoimmune disorder that affects approximately 10 out of every million people in the United States, mainly adults in their late 40s to early 60s, according to the company, but children aged 5-15 years can be affected. The disease is characterized by skin rashes, chronic muscle inflammation, progressive muscle weakness, and risk for mortality that is three times higher than for the general population.
There are no previously approved treatments for dermatomyositis prior to Octagam 10%, which also is indicated for chronic immune thrombocytopenic purpura in adults.
The approval for dermatomyositis was based on the results of a phase 3 randomized, double-blind, placebo-controlled clinical trial (the ProDERM trial) that included 95 adult patients at 36 sites worldwide, with 17 sites in the United States. In the trial, 78.7% of patients with dermatomyositis who were randomized to receive 2 g/kg of Octagam 10% every 4 weeks showed response at 16 weeks, compared with 43.8% of patients who received placebo. Response was based on the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology myositis response criteria. Placebo patients who switched to intravenous immunoglobulin (IVIG) during a trial extension had response rates at week 40 similar to the original patients at week 16.
“The study gives clinicians much more confidence in the efficacy and safety of intravenous immunoglobulin and provides valuable information about what type of patient is best suited for the treatment,” Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh and a member of the ProDERM study Steering Committee, said in the Octapharma statement.
Safety and tolerability were similar to profiles seen with other IVIG medications, according to the statement. The medication does carry a boxed warning from its chronic ITP approval, cautioning about the potential for thrombosis, renal dysfunction, and acute renal failure.
The most common adverse reactions reported by dermatomyositis patients in the ProDERM trial were headache, fever, nausea, vomiting, increased blood pressure, chills, musculoskeletal pain, increased heart rate, dyspnea, and reactions at the infusion sites.
Read the full prescribing information here.
, according to a statement from manufacturer Octapharma USA.
Dermatomyositis is a rare, idiopathic autoimmune disorder that affects approximately 10 out of every million people in the United States, mainly adults in their late 40s to early 60s, according to the company, but children aged 5-15 years can be affected. The disease is characterized by skin rashes, chronic muscle inflammation, progressive muscle weakness, and risk for mortality that is three times higher than for the general population.
There are no previously approved treatments for dermatomyositis prior to Octagam 10%, which also is indicated for chronic immune thrombocytopenic purpura in adults.
The approval for dermatomyositis was based on the results of a phase 3 randomized, double-blind, placebo-controlled clinical trial (the ProDERM trial) that included 95 adult patients at 36 sites worldwide, with 17 sites in the United States. In the trial, 78.7% of patients with dermatomyositis who were randomized to receive 2 g/kg of Octagam 10% every 4 weeks showed response at 16 weeks, compared with 43.8% of patients who received placebo. Response was based on the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology myositis response criteria. Placebo patients who switched to intravenous immunoglobulin (IVIG) during a trial extension had response rates at week 40 similar to the original patients at week 16.
“The study gives clinicians much more confidence in the efficacy and safety of intravenous immunoglobulin and provides valuable information about what type of patient is best suited for the treatment,” Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh and a member of the ProDERM study Steering Committee, said in the Octapharma statement.
Safety and tolerability were similar to profiles seen with other IVIG medications, according to the statement. The medication does carry a boxed warning from its chronic ITP approval, cautioning about the potential for thrombosis, renal dysfunction, and acute renal failure.
The most common adverse reactions reported by dermatomyositis patients in the ProDERM trial were headache, fever, nausea, vomiting, increased blood pressure, chills, musculoskeletal pain, increased heart rate, dyspnea, and reactions at the infusion sites.
Read the full prescribing information here.
, according to a statement from manufacturer Octapharma USA.
Dermatomyositis is a rare, idiopathic autoimmune disorder that affects approximately 10 out of every million people in the United States, mainly adults in their late 40s to early 60s, according to the company, but children aged 5-15 years can be affected. The disease is characterized by skin rashes, chronic muscle inflammation, progressive muscle weakness, and risk for mortality that is three times higher than for the general population.
There are no previously approved treatments for dermatomyositis prior to Octagam 10%, which also is indicated for chronic immune thrombocytopenic purpura in adults.
The approval for dermatomyositis was based on the results of a phase 3 randomized, double-blind, placebo-controlled clinical trial (the ProDERM trial) that included 95 adult patients at 36 sites worldwide, with 17 sites in the United States. In the trial, 78.7% of patients with dermatomyositis who were randomized to receive 2 g/kg of Octagam 10% every 4 weeks showed response at 16 weeks, compared with 43.8% of patients who received placebo. Response was based on the 2016 American College of Rheumatology/European Alliance of Associations for Rheumatology myositis response criteria. Placebo patients who switched to intravenous immunoglobulin (IVIG) during a trial extension had response rates at week 40 similar to the original patients at week 16.
“The study gives clinicians much more confidence in the efficacy and safety of intravenous immunoglobulin and provides valuable information about what type of patient is best suited for the treatment,” Rohit Aggarwal, MD, medical director of the Arthritis and Autoimmunity Center at the University of Pittsburgh and a member of the ProDERM study Steering Committee, said in the Octapharma statement.
Safety and tolerability were similar to profiles seen with other IVIG medications, according to the statement. The medication does carry a boxed warning from its chronic ITP approval, cautioning about the potential for thrombosis, renal dysfunction, and acute renal failure.
The most common adverse reactions reported by dermatomyositis patients in the ProDERM trial were headache, fever, nausea, vomiting, increased blood pressure, chills, musculoskeletal pain, increased heart rate, dyspnea, and reactions at the infusion sites.
Read the full prescribing information here.
FDA to revise statin pregnancy contraindication
The U.S. Food and Drug Administration (FDA) aims to update the labeling on all statins to remove the drugs’ blanket contraindication in all pregnant patients, the agency has announced. The change should reinforce for both physicians and patients that statin use in women with unrecognized pregnancy is unlikely to be harmful, it said.
“Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.”
The revision should emphasize for clinicians “that statins are safe to prescribe in patients who can become pregnant and help them reassure patients with unintended statin exposure in early pregnancy,” the FDA explained.
Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke." That includes women with homozygous familial hypercholesterolemia and those who are prescribed statins for secondary prevention, the agency said.
Clinicians “should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration (FDA) aims to update the labeling on all statins to remove the drugs’ blanket contraindication in all pregnant patients, the agency has announced. The change should reinforce for both physicians and patients that statin use in women with unrecognized pregnancy is unlikely to be harmful, it said.
“Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.”
The revision should emphasize for clinicians “that statins are safe to prescribe in patients who can become pregnant and help them reassure patients with unintended statin exposure in early pregnancy,” the FDA explained.
Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke." That includes women with homozygous familial hypercholesterolemia and those who are prescribed statins for secondary prevention, the agency said.
Clinicians “should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy.”
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration (FDA) aims to update the labeling on all statins to remove the drugs’ blanket contraindication in all pregnant patients, the agency has announced. The change should reinforce for both physicians and patients that statin use in women with unrecognized pregnancy is unlikely to be harmful, it said.
“Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.”
The revision should emphasize for clinicians “that statins are safe to prescribe in patients who can become pregnant and help them reassure patients with unintended statin exposure in early pregnancy,” the FDA explained.
Removal of the broadly worded contraindication should “enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke." That includes women with homozygous familial hypercholesterolemia and those who are prescribed statins for secondary prevention, the agency said.
Clinicians “should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy.”
A version of this article first appeared on Medscape.com.