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Strangulation deaths spur FDA alert on pediatric enteral feeding kits
Enteral feeding kits pose a risk for strangulation in children, according to a safety alert from the U.S. Food and Drug Administration. The safety alert was prompted by two deaths linked to the medical devices.
The alert cites the deaths in 2021 of two toddlers who were strangled by tubes in the feeding sets that had become wrapped around their necks.
Clinicians should discuss the risk of strangulation with colleagues and caregivers and encourage them to take steps to keep tubing away from children as much as possible, the agency advised in a Feb. 8, 2022, safety communication.
“When caring for pediatric patients who receive enteral feeding and as part of an individual risk assessment, be aware of the risk of strangulation from the feeding set tubing and follow protocols to monitor medical line safety,” the FDA warned.
Parents should be aware of the risk and avoid leaving tubing where infants or children can become entangled, to the extent that is possible. They also should tell their child’s health care provider if their child has ever been tangled in the tubing and discuss precautions to ensure that tubing does not get wrapped around the neck, as well as any related concerns.
Enteral feeding sets provide nutrition to people who are unable meet their nutritional needs by eating or swallowing. Tubing delivers nutrition formulas, using gravity or a pump, directly to the stomach or small intestine through the nose, mouth, or an opening in the abdomen.
The two reported deaths involved children under the age of 2 years who were found with tubing wrapped around their necks after brief periods when their caregivers were not directly monitoring them. One report described the unsupervised period as about 10 minutes.
“While the FDA believes that death or serious injury from strangulation with enteral feeding set tubing in children is rare, health care providers and caregivers should be aware that these events can and do occur,” according to the alert. “It is also possible that some cases have not been reported to the FDA.”
Parents and health care providers can report injuries caused by these devices to the FDA.
A version of this article first appeared on Medscape.com.
Enteral feeding kits pose a risk for strangulation in children, according to a safety alert from the U.S. Food and Drug Administration. The safety alert was prompted by two deaths linked to the medical devices.
The alert cites the deaths in 2021 of two toddlers who were strangled by tubes in the feeding sets that had become wrapped around their necks.
Clinicians should discuss the risk of strangulation with colleagues and caregivers and encourage them to take steps to keep tubing away from children as much as possible, the agency advised in a Feb. 8, 2022, safety communication.
“When caring for pediatric patients who receive enteral feeding and as part of an individual risk assessment, be aware of the risk of strangulation from the feeding set tubing and follow protocols to monitor medical line safety,” the FDA warned.
Parents should be aware of the risk and avoid leaving tubing where infants or children can become entangled, to the extent that is possible. They also should tell their child’s health care provider if their child has ever been tangled in the tubing and discuss precautions to ensure that tubing does not get wrapped around the neck, as well as any related concerns.
Enteral feeding sets provide nutrition to people who are unable meet their nutritional needs by eating or swallowing. Tubing delivers nutrition formulas, using gravity or a pump, directly to the stomach or small intestine through the nose, mouth, or an opening in the abdomen.
The two reported deaths involved children under the age of 2 years who were found with tubing wrapped around their necks after brief periods when their caregivers were not directly monitoring them. One report described the unsupervised period as about 10 minutes.
“While the FDA believes that death or serious injury from strangulation with enteral feeding set tubing in children is rare, health care providers and caregivers should be aware that these events can and do occur,” according to the alert. “It is also possible that some cases have not been reported to the FDA.”
Parents and health care providers can report injuries caused by these devices to the FDA.
A version of this article first appeared on Medscape.com.
Enteral feeding kits pose a risk for strangulation in children, according to a safety alert from the U.S. Food and Drug Administration. The safety alert was prompted by two deaths linked to the medical devices.
The alert cites the deaths in 2021 of two toddlers who were strangled by tubes in the feeding sets that had become wrapped around their necks.
Clinicians should discuss the risk of strangulation with colleagues and caregivers and encourage them to take steps to keep tubing away from children as much as possible, the agency advised in a Feb. 8, 2022, safety communication.
“When caring for pediatric patients who receive enteral feeding and as part of an individual risk assessment, be aware of the risk of strangulation from the feeding set tubing and follow protocols to monitor medical line safety,” the FDA warned.
Parents should be aware of the risk and avoid leaving tubing where infants or children can become entangled, to the extent that is possible. They also should tell their child’s health care provider if their child has ever been tangled in the tubing and discuss precautions to ensure that tubing does not get wrapped around the neck, as well as any related concerns.
Enteral feeding sets provide nutrition to people who are unable meet their nutritional needs by eating or swallowing. Tubing delivers nutrition formulas, using gravity or a pump, directly to the stomach or small intestine through the nose, mouth, or an opening in the abdomen.
The two reported deaths involved children under the age of 2 years who were found with tubing wrapped around their necks after brief periods when their caregivers were not directly monitoring them. One report described the unsupervised period as about 10 minutes.
“While the FDA believes that death or serious injury from strangulation with enteral feeding set tubing in children is rare, health care providers and caregivers should be aware that these events can and do occur,” according to the alert. “It is also possible that some cases have not been reported to the FDA.”
Parents and health care providers can report injuries caused by these devices to the FDA.
A version of this article first appeared on Medscape.com.
Dupilumab under FDA review for atopic dermatitis in children aged 6 months to 5 years
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
FROM THE FDA
Endocrine Society and others to FDA: Restrict BPA
The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.
The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.
It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
Average American exposed to 5,000 times the safe level of BPA
The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.
“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.
In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.
In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”
“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.
The FDA is expected to decide within the next few days whether to open a docket to accept comments.
A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.
A version of this article first appeared on Medscape.com.
The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.
The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.
It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
Average American exposed to 5,000 times the safe level of BPA
The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.
“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.
In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.
In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”
“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.
The FDA is expected to decide within the next few days whether to open a docket to accept comments.
A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.
A version of this article first appeared on Medscape.com.
The chemical is used to make plastics in items such as food containers, pitchers, and inner linings of metal products. Small amounts of BPA can leak into food and beverages.
The petition points to a December 2021 report by the European Food Safety Authority titled: “Re-evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs,” which summarizes evidence gathered since 2013.
It concludes that “there is a health concern from BPA exposure for all age groups.” Specific concerns include harm to the immune system and male and female reproductive systems.
Average American exposed to 5,000 times the safe level of BPA
The EFSA established a new “tolerable daily intake” of BPA of 0.04 ng/kg of body weight per day. By contrast, in 2014 the FDA estimated that the mean BPA intake for the U.S. population older than 2 years was 200 ng/kg bw/day and that the 90th percentile for BPA intake was 500 ng/kg of body weight per day.
“Using FDA’s own exposure estimates, the average American is exposed to more than 5000 times the safe level of 0.04 ng BPA/kg [body weight per day] set by the EFSA expert panel. Without a doubt, these values constitute a high health risk and support the conclusion that uses of BPA are not safe ... Given the magnitude of the overexposure, we request an expedited review by FDA,” the petition reads.
In addition to the Endocrine Society, which has long warned about the dangers of endocrine-disrupting chemicals, other signatories to the petition include the Environmental Defense Fund, Breast Cancer Prevention Partners, Clean Water Action/Clean Water Fund, Consumer Reports, Environmental Working Group, Healthy Babies Bright Futures, and the former director of the National Institute of Environmental Health Sciences and National Toxicology Program.
In a statement, Endocrine Society BPA expert Heather Patisaul, PhD, of North Carolina University, Raleigh, said the report’s findings “are extremely concerning and prove the point that even very low levels of BPA exposure can be harmful and lead to issues with reproductive health, breast cancer risk, behavior, and metabolism.”
“The FDA needs to acknowledge the science behind endocrine-disrupting chemicals and act accordingly to protect public health,” she urged.
The FDA is expected to decide within the next few days whether to open a docket to accept comments.
A final decision could take 6 months or longer, an Endocrine Society spokesperson told this news organization.
A version of this article first appeared on Medscape.com.
Two emerging drugs exacerbating opioid crisis
Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.
Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.
On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.
Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.
“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
Tennessee data reflect national problem
Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.
Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.
“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
How to identify substances, manage overdoses
The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.
They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.
While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.
The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”
Dr. Fuehrlein had no disclosures.
Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.
Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.
On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.
Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.
“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
Tennessee data reflect national problem
Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.
Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.
“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
How to identify substances, manage overdoses
The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.
They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.
While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.
The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”
Dr. Fuehrlein had no disclosures.
Two illicit drugs are contributing to a sharp rise in fentanyl-related deaths, a new study from the Centers for Disease Control and Prevention shows.
Para-fluorofentanyl, a schedule I substance often found in heroin packets and counterfeit pills, is making a comeback on the illicit drug market, Jordan Trecki, PhD, and associates reported in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (2022 Jan 28;71[4]:153-5). U.S. medical examiner reports and national law enforcement seizure data point to a rise in encounters of this drug along with metonitazene, a benzimidazole-opioid, in combination with fentanyl.
On their own, para-fluorofentanyl and metonitazene can kill the user through respiratory depression. Combinations of these substances and other opioids, including fentanyl-related compounds or adulterants, “pose an even greater potential harm to the patient than previously observed,” reported Dr. Trecki, a pharmacologist affiliated with the Drug Enforcement Administration, and colleagues.
Opioids contribute to about 75% of all U.S. drug overdose deaths, which rose by 28.5% during 2020-2021, according to the National Center for Health Statistics. And fentanyl is replacing heroin as the primary drug of use, said addiction specialist Brian Fuehrlein, MD, PhD, in an interview.
“For patients with stimulant use disorder and even cannabis use disorder, fentanyl is becoming more and more common as an adulterant in those substances, often resulting in inadvertent use. Hence, fentanyl and fentanyl-like drugs and fentanyl analogues are becoming increasingly common and important,” said Dr. Fuehrlein, director of the psychiatric emergency room at the VA Connecticut Healthcare System. He was not involved with the MMWR study.
Tennessee data reflect national problem
Recent data from a medical examiner in Knoxville, Tenn., illustrate what might be happening nationwide with those two emerging substances.
Over the last 2 years, the Knox County Regional Forensic Center has identified para-fluorofentanyl in the toxicology results of drug overdose victims, and metonitazene – either on its own or in combination with fentanyl and para-fluorofentanyl. Fentanyl appeared in 562 or 73% of 770 unintentional drug overdose deaths from November 2020 to August 2021. Forty-eight of these cases involved para-fluorofentanyl, and 26 involved metonitazene.
“Although the percentage of law enforcement encounters with these substances in Tennessee decreased relative to the national total percentage within this time frame, the increase in encounters both within Tennessee and nationally reflect an increased distribution of para-fluorofentanyl and metonitazene throughout the United States,” the authors reported.
How to identify substances, manage overdoses
The authors encouraged physicians, labs, and medical examiners to be on the lookout for these two substances either in the emergency department or when identifying the cause of drug overdose deaths.
They also advised that stronger opioids, such as fentanyl, para-fluorofentanyl, metonitazene, or other benzimidazoles may warrant additional doses of the opioid-reversal drug naloxone.
While he hasn’t personally seen any of these drugs in his practice, “I would assume that these are on the rise due to inexpensive cost to manufacture and potency of effect,” said Dr. Fuehrlein, also an associate professor of psychiatry at Yale University, New Haven, Conn.
The need for additional naloxone to manage acute overdoses is a key takeaway of the MMWR paper, he added. Clinicians should also educate patients about harm reduction strategies to avoid overdose death when using potentially powerful and unknown drugs. “Things like start low and go slow, buy from the same supplier, do not use opioids with alcohol or benzos, have Narcan available, do not use alone, etc.”
Dr. Fuehrlein had no disclosures.
FDA approves first-ever drug for cold agglutinin disease
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
A new drug has become the first and only treatment for people with cold agglutinin disease (CAD) that is approved by the U.S. Food and Drug Administration.
CAD is a rare autoimmune hemolytic anemia, affecting about 5,000 people in the United States. It is caused by antibodies binding to the surface of red blood cells, which starts a process that causes the body’s immune system to mistakenly attack healthy red blood cells and cause their rupture (hemolysis). This can lead to severe anemia, which is often treated by blood transfusions.
“For people living with cold agglutinin disease, it is as if their body’s immune system is waging a war on itself. The relentless destruction of healthy red blood cells is a daily, silent reality for people with CAD. For the first time, we have a treatment that targets complement-mediated hemolysis, which is the underlying cause of the red blood cell destruction in many CAD patients,” commented Catherine Broome, MD, associate professor of medicine at Georgetown University Lombardi Comprehensive Cancer Center, in a company press release.
Dr. Broome was the principal investigator in the CARDINAL study, which was the basis for the new approval. In this pivotal study, patients treated with sutimlimab had an improvement in anemia as measured by hemoglobin (Hgb) and bilirubin levels, she commented in the company statement.
The CARDINAL study was a 26-week open-label, single-arm phase 3 study conducted in 24 patients with CAD who had recent history of blood transfusion.
The primary efficacy endpoint was a composite defined as the proportion of patients who achieved normalization of Hgb level greater than or equal to 12 g/dL or demonstrated an increase from baseline in Hgb level greater than or equal to 2 g/dL at the treatment assessment time point (mean value from weeks 23, 25, and 26) and no blood transfusion from weeks 5 through 26.
More than half of the patients (13 of 24, 54%) met the composite primary endpoint criteria, with 17 of 24 (71%) patients remaining transfusion-free after week 5. Most patients (22 of 24, 92%) did not use other CAD-related treatments.
For the secondary measures on disease process, patients enrolled in the trial experienced a mean increase in Hgb level of 2.29 g/dL at week 3 and 3.18 g/dL at the 26-week treatment assessment time points (increasing from the mean baseline level of 8.6 g/dL). In addition, there was a mean reduction in bilirubin levels (n = 14) of -2.23 mg/dL from a mean baseline level of 3.23 mg/dL.
The most common adverse reactions occurring in 10% or more of patients were respiratory tract infection, viral infection, diarrhea, dyspepsia, cough, arthralgia, arthritis, and peripheral edema. Serious adverse reactions were reported in 3 of 24 (13%) patients, and these included streptococcal sepsis and staphylococcal wound infection (n = 1), arthralgia (n = 1), and respiratory tract infection (n = 1).
None of the adverse reactions led to discontinuation of the drug, the company noted. Dosage interruptions due to an adverse reaction occurred in 4 of 24 (17%) patients who received the drug.
The recommended dose is based on body weight (6,500 mg for people 39-75 kg and 7,500 mg for people greater than 75 kg). The drug is administered intravenously weekly for the first 2 weeks with administration every 2 weeks thereafter.
Full prescribing information is available here.
The product is a humanized monoclonal antibody that is designed to selectively target and inhibit C1s in the classical complement pathway, which is part of the innate immune system. By blocking C1s, Enjaymo inhibits the activation of the complement cascade in the immune system and inhibits C1-activated hemolysis in CAD to prevent the abnormal destruction of healthy red blood cells. Enjaymo does not inhibit the lectin and alternative pathways, the company noted.
In the U.S., Enjaymo received FDA breakthrough therapy and orphan drug designation, as well as priority review. The product is awaiting approval in Europe and Japan.
Sanofi says the product is expected to be available in the United States in the coming weeks, with a list price, or wholesale acquisition cost, of $1,800 per vial. Actual costs to patients are generally anticipated to be lower, as the list price does not reflect insurance coverage, copay support, or financial assistance from patient support programs. The company offers support for eligible patients on 1-833-223-2428.
A version of this article first appeared on Medscape.com.
New CDC webpage aims to reduce maternal deaths
The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.
As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.
The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.
“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”
Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.
Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.
Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”
According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
During maternity care
Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.
These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.
Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.
The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.
But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
Postpartum care
Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.
While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.
“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”
Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
Nonobstetric settings
Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.
Support materials
Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.
The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.
The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.
ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.
Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.
The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.
As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.
The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.
“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”
Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.
Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.
Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”
According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
During maternity care
Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.
These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.
Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.
The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.
But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
Postpartum care
Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.
While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.
“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”
Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
Nonobstetric settings
Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.
Support materials
Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.
The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.
The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.
ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.
Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.
The Centers for Disease Control and Prevention is providing new online materials in a comprehensive campaign to reduce maternal mortality and postpartum complications.
As part of the CDC’s Hear Her campaign, launched last year, the webpage resources are designed to lower the United States’s more than 700 annual pregnancy-related deaths, of which two-thirds could be prevented.
The United States has the highest maternal death rate of any industrialized country and is the only developed nation in which that rate is rising.
“Unfortunately, the number of deaths occurring during pregnancy around and after delivery has not improved over time,” said obstetrician-gynecologist Romeo Galang, MD, MPH, acting chief medical officer and associate director for health equity in CDC’s division of reproductive health in Atlanta. “But no matter when they occur, two of three are preventable.”
Each year, some 50,000 mothers experience adverse pregnancy-related effects that can affect their long-term health. According to the American College of Obstetricians and Gynecologists, approximately one in three maternal deaths occur within 1 week to 1 year of delivery.
Self-harm and drug overdoses are leading causes of maternal death and non-White minority mothers are more likely than Whites to die.
Other causes are postpartum complications of hypertension, even postpartum preeclampsia, cardiovascular problems, and infectious illness, said Dr. Galang. “These are all things we may see after pregnancy and we want to monitor for them and make women aware of them.”
According to the CDC, in the first week after delivery hemorrhage, hypertensive disorders of pregnancy, and infection were leading causes of death, while cardiomyopathy was the predominant cause 1 week to 1 year after delivery.
During maternity care
Obstetricians, obstetric nurses, midwives, and nurse practitioners are uniquely positioned to educate pregnant and postpartum patients about recognizing urgent maternal warning signs, the CDC stated.
These harbingers of potential trouble include chronic or worsening headache, dizziness or faintness, altered vision, a fever of 100.4° F or higher, severely swollen hands or feet, thoughts of self-harming or harming the baby, and respiratory distress. Chest pain or tachycardia, a swollen abdomen, belly pain, nausea and vomiting, and extreme fatigue are also indicators of potential trouble.
Signs that occurred during pregnancy range from cessation or slowing of fetal movement to vaginal bleeding and fluid leakage.
The success of the Hear Her campaign will rely on an environment of trust, and it is important for obstetric care providers to build trust with patients at the outset of prenatal care and encourage mothers to share any concerns, the CDC stated. Ultimately, the best person to know her body is the woman herself, and her concerns should be heard and addressed.
But getting women to report symptoms may not be a given. “Many women and their family will attribute symptoms to the fact they’re having or have just had a baby, and there are other factors related to individual care providers and the health care systems they practice in,” Dr. Galang said.
Postpartum care
Since pregnancy complications may affect women for as long as a year after delivery, pediatricians and pediatric nurses can be an important lifeline for mothers needing postpartum care. Infant check-ups are an opportune time for staff to ask mothers how they are feeling and listen and observe carefully to identify urgent maternal warning signs.
While physicians often feel inundated by awareness campaigns, this is one that Rachel Sinkey, MD, of the department of obstetrics and gynecology and division of maternal-fetal medicine at the University of Alabama at Birmingham, wants to see remain top of mind. “It’s an excellent campaign. It’s spot on,” she said in an interview.
“The understanding that the U.S. has the highest maternal mortality rate in the developed world has rightly gained a lot of media attention,” she said. “The death of a mother affects the child, the family, and the entire community. Maternal death is a marker of the health of the community.”
Dr. Sinkey has seen mothers die postpartum of infection and heart problems. Self-harm, psychiatric disorders, and opioid overdoses are also leading causes of maternal death in Alabama. “If we can recognize these mothers and get them into good care, we can reduce some of the overdose deaths,” she said. Unfortunately, however, it’s not always a simple matter of timely recognition and referral, she said. “Some patients don’t have the insurance coverage they need to get access to care.”
Nonobstetric settings
Beyond the context of maternity-specific care, other medical professionals can help, the CDC said. Emergency department staff, paramedics, urgent care staff, primary care providers, and mental health professionals can all ask women about their recent pregnancy status and recognize the signs and symptoms of pregnancy-related complications. Health care professionals should specifically ask patients if they are pregnant or were pregnant in the past year, the CDC advised.
Support materials
Campaign materials available from the website include posters, palm cards, graphics, and social media content in English and Spanish as well as other languages ranging from Arabic to Tagalog and Vietnamese. There are separate guides to help mothers recognize warning signs and comfortably raise issues with their health care providers, as well as guides for providers to ensure respectful listening followed by appropriate action and for women’s partners and family members. A graphic poster, “Pregnant now or within the last year?” clearly illustrates symptoms worth discussing.
The site also connects health care professionals with clinical resources and tools from a variety of complementary stakeholder organizations.
The CDC is partnering in this effort with ACOG and many other medical organizations from the American Academy of Family Physicians and the American Society of Addiction Medicine to the Society for Maternal-Fetal Medicine. The goal is to expand readiness across multiple health care settings to manage obstetric emergencies during pregnancy and the postpartum period.
ACOG’s initiative is called Commitment to Action: Eliminating Preventable Maternal Mortality.
Dr. Sinkey had no competing interests with regard to her comments. Dr. Galang, as a government employee, had no conflicts of interest.
FDA approves 2-month dosing of injectable HIV drug Cabenuva
Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.
Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.
The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”
This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).
The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.
A version of this article first appeared on Medscape.com.
Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.
Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.
The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”
This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).
The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.
A version of this article first appeared on Medscape.com.
Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.
Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.
The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”
This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).
The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.
A version of this article first appeared on Medscape.com.
FDA investigates possible increased risk of death with lymphoma drug
The FDA granted accelerated approval to umbralisib in February 2021 for patients with two types of lymphoma: Adults with relapsed or refractory marginal zone lymphoma who received at least one prior therapy, and those with relapsed or refractory follicular lymphoma who received at least three prior therapies.
According to the FDA, the possible increased risk of death arose from early findings in a phase 3 trial evaluating the drug in a related type of cancer: chronic lymphocytic leukemia.
“Because of the seriousness of this safety concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial, we are alerting patients and health care professionals that we are reevaluating this risk against the benefits of Ukoniq [umbralisib] for its approved uses,” the FDA safety communication states.
The FDA said it performed an initial review of data from the phase 3, randomized controlled UNITY trial, which is evaluating the efficacy of umbralisib plus a monoclonal antibody in patients with chronic lymphocytic leukemia.
“The results showed a possible increased risk of death in patients receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody compared to the control arm,” according to the FDA. “Those receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody also experienced more serious adverse events than those in the control arm.”
Although the drug has not been approved for patients with chronic lymphocytic leukemia, the FDA believes the findings could “have implications for its approved uses” in marginal zone lymphoma and follicular lymphoma.
However, the phase 2 trial that led to February 2021 approvals found the drug’s safety profile to be “manageable,” with serious adverse reactions reported in 18% of patients receiving the dual oral inhibitor of phosphoinositide 3 kinase delta and casein kinase 1 epsilon. These adverse reactions included diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%); however, no elevated risk of death was indicated in that analysis.
The FDA noted it will continue to evaluate the results from the phase 3 UNITY trial in chronic lymphocytic leukemia and has suspended enrollment of new patients in other ongoing clinical trials of the drug.
The FDA stated that it would communicate its “final conclusions and recommendations when we have completed our review.” In the meantime, the agency asks health care professionals to review how patients receiving umbralisib are faring and discuss “the risks and benefits of continuing” versus switching to other treatments.
The FDA also asks clinicians and patients to report side effects involving the drug to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
The FDA granted accelerated approval to umbralisib in February 2021 for patients with two types of lymphoma: Adults with relapsed or refractory marginal zone lymphoma who received at least one prior therapy, and those with relapsed or refractory follicular lymphoma who received at least three prior therapies.
According to the FDA, the possible increased risk of death arose from early findings in a phase 3 trial evaluating the drug in a related type of cancer: chronic lymphocytic leukemia.
“Because of the seriousness of this safety concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial, we are alerting patients and health care professionals that we are reevaluating this risk against the benefits of Ukoniq [umbralisib] for its approved uses,” the FDA safety communication states.
The FDA said it performed an initial review of data from the phase 3, randomized controlled UNITY trial, which is evaluating the efficacy of umbralisib plus a monoclonal antibody in patients with chronic lymphocytic leukemia.
“The results showed a possible increased risk of death in patients receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody compared to the control arm,” according to the FDA. “Those receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody also experienced more serious adverse events than those in the control arm.”
Although the drug has not been approved for patients with chronic lymphocytic leukemia, the FDA believes the findings could “have implications for its approved uses” in marginal zone lymphoma and follicular lymphoma.
However, the phase 2 trial that led to February 2021 approvals found the drug’s safety profile to be “manageable,” with serious adverse reactions reported in 18% of patients receiving the dual oral inhibitor of phosphoinositide 3 kinase delta and casein kinase 1 epsilon. These adverse reactions included diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%); however, no elevated risk of death was indicated in that analysis.
The FDA noted it will continue to evaluate the results from the phase 3 UNITY trial in chronic lymphocytic leukemia and has suspended enrollment of new patients in other ongoing clinical trials of the drug.
The FDA stated that it would communicate its “final conclusions and recommendations when we have completed our review.” In the meantime, the agency asks health care professionals to review how patients receiving umbralisib are faring and discuss “the risks and benefits of continuing” versus switching to other treatments.
The FDA also asks clinicians and patients to report side effects involving the drug to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
The FDA granted accelerated approval to umbralisib in February 2021 for patients with two types of lymphoma: Adults with relapsed or refractory marginal zone lymphoma who received at least one prior therapy, and those with relapsed or refractory follicular lymphoma who received at least three prior therapies.
According to the FDA, the possible increased risk of death arose from early findings in a phase 3 trial evaluating the drug in a related type of cancer: chronic lymphocytic leukemia.
“Because of the seriousness of this safety concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial, we are alerting patients and health care professionals that we are reevaluating this risk against the benefits of Ukoniq [umbralisib] for its approved uses,” the FDA safety communication states.
The FDA said it performed an initial review of data from the phase 3, randomized controlled UNITY trial, which is evaluating the efficacy of umbralisib plus a monoclonal antibody in patients with chronic lymphocytic leukemia.
“The results showed a possible increased risk of death in patients receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody compared to the control arm,” according to the FDA. “Those receiving the combination of Ukoniq [umbralisib] and the monoclonal antibody also experienced more serious adverse events than those in the control arm.”
Although the drug has not been approved for patients with chronic lymphocytic leukemia, the FDA believes the findings could “have implications for its approved uses” in marginal zone lymphoma and follicular lymphoma.
However, the phase 2 trial that led to February 2021 approvals found the drug’s safety profile to be “manageable,” with serious adverse reactions reported in 18% of patients receiving the dual oral inhibitor of phosphoinositide 3 kinase delta and casein kinase 1 epsilon. These adverse reactions included diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%); however, no elevated risk of death was indicated in that analysis.
The FDA noted it will continue to evaluate the results from the phase 3 UNITY trial in chronic lymphocytic leukemia and has suspended enrollment of new patients in other ongoing clinical trials of the drug.
The FDA stated that it would communicate its “final conclusions and recommendations when we have completed our review.” In the meantime, the agency asks health care professionals to review how patients receiving umbralisib are faring and discuss “the risks and benefits of continuing” versus switching to other treatments.
The FDA also asks clinicians and patients to report side effects involving the drug to the FDA MedWatch program.
A version of this article first appeared on Medscape.com.
Boosted Americans 97 times less likely to die of COVID-19 than unvaccinated
according to a new update from the CDC.
In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.
“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.
“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.
Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.
“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.
Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.
Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.
“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”
About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.
The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.
“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.
A version of this article first appeared on WebMD.com.
according to a new update from the CDC.
In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.
“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.
“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.
Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.
“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.
Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.
Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.
“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”
About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.
The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.
“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.
A version of this article first appeared on WebMD.com.
according to a new update from the CDC.
In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.
“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.
“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.
Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.
“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.
Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.
Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.
“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”
About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.
The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.
“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.
A version of this article first appeared on WebMD.com.
Surrogate endpoints acceptable in AML trials, says FDA
The Food and Drug Administration has been harshly criticized for using surrogate endpoints in clinical trials in its approval of new drugs, and especially so in oncology, where critics have argued that the only truly meaningful endpoint is overall survival (OS).
But the FDA is now fighting back and is arguing that in certain cases surrogate endpoints do translate to overall survival benefits. A case in point is in clinical trials of new treatments being investigated in patients newly diagnosed with acute myeloid leukemia (AML).
The results show that these particular surrogate endpoints do have real value in predicting the efficacy of drugs for the treatment of newly diagnosed AML, they concluded.
“To our knowledge, our results represent the first direct examination of the relationship of response rate and EFS to OS using trial-level and patient-level data in patients with newly diagnosed AML treated with intensive induction chemotherapy,” the FDA investigators commented.
“The results support the FDA’s acceptance of EFS as a clinical benefit endpoint supportive of traditional approval for treatments with curative intent,” they added.
The analysis was published online on Dec. 10, 2021, in the Journal of Clinical Oncology.
“The central finding of the article, that both EFS and the CR rate are reliably associated with improved OS, is of immediate relevance and indicates that these parameters represent acceptable and appropriate surrogate endpoints for clinical trials of AML,” Courtney DiNardo, MD, University of Texas MD Anderson Cancer Center, Houston, and Daniel Pollyea, MD, University of Colorado at Denver, Aurora, wrote in an accompanying editorial.
“The establishment of CR and EFS as appropriate surrogate endpoints for patients with newly diagnosed AML receiving intensive chemotherapy will allow earlier evaluation of novel therapies and speed the delivery of safe and effective therapies to our patients,” they added.
Analysis of clinical trials submitted for approval
The FDA investigators conducted an analysis of eight trials that had been submitted to the agency for licensing approval between 2007 and 2011. Together, the trials included a total of 4,482 patients with newly diagnosed AML.
Five trials evaluated gemtuzumab ozogamicin (Mylotarg), while two trials evaluated a daunorubicin and cytarabine liposome injection, also known as CPX-351 (Vyxeos), and one trial evaluated midostaurin (RYDAPT).
“All were approved in combination with, or for use as, intensive induction chemotherapy in patients with newly diagnosed AML,” the team wrote. Both trial-level and patient-level associations between responses, EFS, and OS were evaluated.
The association between the hazard ratio for OS and the odds ratio for CR at the trial level was “moderate.” The association between the HR for OS and the OR for lesser response rates – namely, CR with incomplete hematologic recovery (CRi) and CR with incomplete platelet recovery (CRp) – was similarly moderate, as investigators note.
On the other hand, while the associations between the HR for OS and the HR for EFS were again moderate, “on the basis of the harmonized primary definition of EFS across trials, the association became stronger,” the authors reported. The harmonized definition of EFS across the trials included time from random assignment to treatment failure, relapse from CR, or death from any cause, whichever occurred earlier.
The FDA authors cautioned that a significant number of patients who relapsed did not die during the course of the clinical trial, resulting in a considerably longer OS, compared with EFS in some patients. However, to further explore the relationship between response and survival, a patient-level analysis of response – namely, CR versus CRi or CRp versus no response – was performed.”Patients who achieved a CR had a [27%] better OS, compared with patients whose best response was CRi or CRp,” the authors noted.
Patients who achieved a CRi or a CRp as their best response still had a 54% better OS, compared with patients who achieved no response, irrespective of the treatment received, they added.
Interestingly enough, a small number of patients who had no response to treatment also experienced prolonged survival, possibly because of successful second-line therapy, the authors speculated.
Effective salvage therapies
Commenting further in their editorial, Dr. DiNardo and Dr. Pollyea wrote that, given that there are now multiple effective salvage therapies for the treatment of AML, an OS endpoint no longer solely reflects the effectiveness of an initial therapy, as survival will also be affected by subsequent lines of AML-directed treatment.
“Accordingly, OS should no longer be considered the sole determinant of the value of a new therapy,” the editorialists emphasized.
Furthermore, as the treatment of AML is increasingly based on biologically defined and differentially targeted subsets, “the required sample sizes and timelines to run a proper randomized, phase 3 study for an OS end point of a rare AML subset become logistically untenable,” they wrote.
That said, the editorialists felt the fact that FDA employees performed this meta-analysis at all was “highly laudable.” “It is, moreover, gratifying to know that the experiences of clinical trial participants can be maximized beyond the original contributions made to the studies in which they originally volunteered,” the editorialists observed.
“In the United States, this example should inspire investigators and industry partners to prioritize similar analyses with their [own] data sets,” they added.
Dr. Norsworthy, Dr. DiNardo, and Dr. Pollyea disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has been harshly criticized for using surrogate endpoints in clinical trials in its approval of new drugs, and especially so in oncology, where critics have argued that the only truly meaningful endpoint is overall survival (OS).
But the FDA is now fighting back and is arguing that in certain cases surrogate endpoints do translate to overall survival benefits. A case in point is in clinical trials of new treatments being investigated in patients newly diagnosed with acute myeloid leukemia (AML).
The results show that these particular surrogate endpoints do have real value in predicting the efficacy of drugs for the treatment of newly diagnosed AML, they concluded.
“To our knowledge, our results represent the first direct examination of the relationship of response rate and EFS to OS using trial-level and patient-level data in patients with newly diagnosed AML treated with intensive induction chemotherapy,” the FDA investigators commented.
“The results support the FDA’s acceptance of EFS as a clinical benefit endpoint supportive of traditional approval for treatments with curative intent,” they added.
The analysis was published online on Dec. 10, 2021, in the Journal of Clinical Oncology.
“The central finding of the article, that both EFS and the CR rate are reliably associated with improved OS, is of immediate relevance and indicates that these parameters represent acceptable and appropriate surrogate endpoints for clinical trials of AML,” Courtney DiNardo, MD, University of Texas MD Anderson Cancer Center, Houston, and Daniel Pollyea, MD, University of Colorado at Denver, Aurora, wrote in an accompanying editorial.
“The establishment of CR and EFS as appropriate surrogate endpoints for patients with newly diagnosed AML receiving intensive chemotherapy will allow earlier evaluation of novel therapies and speed the delivery of safe and effective therapies to our patients,” they added.
Analysis of clinical trials submitted for approval
The FDA investigators conducted an analysis of eight trials that had been submitted to the agency for licensing approval between 2007 and 2011. Together, the trials included a total of 4,482 patients with newly diagnosed AML.
Five trials evaluated gemtuzumab ozogamicin (Mylotarg), while two trials evaluated a daunorubicin and cytarabine liposome injection, also known as CPX-351 (Vyxeos), and one trial evaluated midostaurin (RYDAPT).
“All were approved in combination with, or for use as, intensive induction chemotherapy in patients with newly diagnosed AML,” the team wrote. Both trial-level and patient-level associations between responses, EFS, and OS were evaluated.
The association between the hazard ratio for OS and the odds ratio for CR at the trial level was “moderate.” The association between the HR for OS and the OR for lesser response rates – namely, CR with incomplete hematologic recovery (CRi) and CR with incomplete platelet recovery (CRp) – was similarly moderate, as investigators note.
On the other hand, while the associations between the HR for OS and the HR for EFS were again moderate, “on the basis of the harmonized primary definition of EFS across trials, the association became stronger,” the authors reported. The harmonized definition of EFS across the trials included time from random assignment to treatment failure, relapse from CR, or death from any cause, whichever occurred earlier.
The FDA authors cautioned that a significant number of patients who relapsed did not die during the course of the clinical trial, resulting in a considerably longer OS, compared with EFS in some patients. However, to further explore the relationship between response and survival, a patient-level analysis of response – namely, CR versus CRi or CRp versus no response – was performed.”Patients who achieved a CR had a [27%] better OS, compared with patients whose best response was CRi or CRp,” the authors noted.
Patients who achieved a CRi or a CRp as their best response still had a 54% better OS, compared with patients who achieved no response, irrespective of the treatment received, they added.
Interestingly enough, a small number of patients who had no response to treatment also experienced prolonged survival, possibly because of successful second-line therapy, the authors speculated.
Effective salvage therapies
Commenting further in their editorial, Dr. DiNardo and Dr. Pollyea wrote that, given that there are now multiple effective salvage therapies for the treatment of AML, an OS endpoint no longer solely reflects the effectiveness of an initial therapy, as survival will also be affected by subsequent lines of AML-directed treatment.
“Accordingly, OS should no longer be considered the sole determinant of the value of a new therapy,” the editorialists emphasized.
Furthermore, as the treatment of AML is increasingly based on biologically defined and differentially targeted subsets, “the required sample sizes and timelines to run a proper randomized, phase 3 study for an OS end point of a rare AML subset become logistically untenable,” they wrote.
That said, the editorialists felt the fact that FDA employees performed this meta-analysis at all was “highly laudable.” “It is, moreover, gratifying to know that the experiences of clinical trial participants can be maximized beyond the original contributions made to the studies in which they originally volunteered,” the editorialists observed.
“In the United States, this example should inspire investigators and industry partners to prioritize similar analyses with their [own] data sets,” they added.
Dr. Norsworthy, Dr. DiNardo, and Dr. Pollyea disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has been harshly criticized for using surrogate endpoints in clinical trials in its approval of new drugs, and especially so in oncology, where critics have argued that the only truly meaningful endpoint is overall survival (OS).
But the FDA is now fighting back and is arguing that in certain cases surrogate endpoints do translate to overall survival benefits. A case in point is in clinical trials of new treatments being investigated in patients newly diagnosed with acute myeloid leukemia (AML).
The results show that these particular surrogate endpoints do have real value in predicting the efficacy of drugs for the treatment of newly diagnosed AML, they concluded.
“To our knowledge, our results represent the first direct examination of the relationship of response rate and EFS to OS using trial-level and patient-level data in patients with newly diagnosed AML treated with intensive induction chemotherapy,” the FDA investigators commented.
“The results support the FDA’s acceptance of EFS as a clinical benefit endpoint supportive of traditional approval for treatments with curative intent,” they added.
The analysis was published online on Dec. 10, 2021, in the Journal of Clinical Oncology.
“The central finding of the article, that both EFS and the CR rate are reliably associated with improved OS, is of immediate relevance and indicates that these parameters represent acceptable and appropriate surrogate endpoints for clinical trials of AML,” Courtney DiNardo, MD, University of Texas MD Anderson Cancer Center, Houston, and Daniel Pollyea, MD, University of Colorado at Denver, Aurora, wrote in an accompanying editorial.
“The establishment of CR and EFS as appropriate surrogate endpoints for patients with newly diagnosed AML receiving intensive chemotherapy will allow earlier evaluation of novel therapies and speed the delivery of safe and effective therapies to our patients,” they added.
Analysis of clinical trials submitted for approval
The FDA investigators conducted an analysis of eight trials that had been submitted to the agency for licensing approval between 2007 and 2011. Together, the trials included a total of 4,482 patients with newly diagnosed AML.
Five trials evaluated gemtuzumab ozogamicin (Mylotarg), while two trials evaluated a daunorubicin and cytarabine liposome injection, also known as CPX-351 (Vyxeos), and one trial evaluated midostaurin (RYDAPT).
“All were approved in combination with, or for use as, intensive induction chemotherapy in patients with newly diagnosed AML,” the team wrote. Both trial-level and patient-level associations between responses, EFS, and OS were evaluated.
The association between the hazard ratio for OS and the odds ratio for CR at the trial level was “moderate.” The association between the HR for OS and the OR for lesser response rates – namely, CR with incomplete hematologic recovery (CRi) and CR with incomplete platelet recovery (CRp) – was similarly moderate, as investigators note.
On the other hand, while the associations between the HR for OS and the HR for EFS were again moderate, “on the basis of the harmonized primary definition of EFS across trials, the association became stronger,” the authors reported. The harmonized definition of EFS across the trials included time from random assignment to treatment failure, relapse from CR, or death from any cause, whichever occurred earlier.
The FDA authors cautioned that a significant number of patients who relapsed did not die during the course of the clinical trial, resulting in a considerably longer OS, compared with EFS in some patients. However, to further explore the relationship between response and survival, a patient-level analysis of response – namely, CR versus CRi or CRp versus no response – was performed.”Patients who achieved a CR had a [27%] better OS, compared with patients whose best response was CRi or CRp,” the authors noted.
Patients who achieved a CRi or a CRp as their best response still had a 54% better OS, compared with patients who achieved no response, irrespective of the treatment received, they added.
Interestingly enough, a small number of patients who had no response to treatment also experienced prolonged survival, possibly because of successful second-line therapy, the authors speculated.
Effective salvage therapies
Commenting further in their editorial, Dr. DiNardo and Dr. Pollyea wrote that, given that there are now multiple effective salvage therapies for the treatment of AML, an OS endpoint no longer solely reflects the effectiveness of an initial therapy, as survival will also be affected by subsequent lines of AML-directed treatment.
“Accordingly, OS should no longer be considered the sole determinant of the value of a new therapy,” the editorialists emphasized.
Furthermore, as the treatment of AML is increasingly based on biologically defined and differentially targeted subsets, “the required sample sizes and timelines to run a proper randomized, phase 3 study for an OS end point of a rare AML subset become logistically untenable,” they wrote.
That said, the editorialists felt the fact that FDA employees performed this meta-analysis at all was “highly laudable.” “It is, moreover, gratifying to know that the experiences of clinical trial participants can be maximized beyond the original contributions made to the studies in which they originally volunteered,” the editorialists observed.
“In the United States, this example should inspire investigators and industry partners to prioritize similar analyses with their [own] data sets,” they added.
Dr. Norsworthy, Dr. DiNardo, and Dr. Pollyea disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ONCOLOGY