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Vaccine gets orphan designation for ATLL
The European Medicines Agency (EMA) has granted orphan drug designation for a therapeutic vaccine candidate known as THV02 to treat adult T-cell leukemia/lymphoma (ATLL).
THV02 is an experimental treatment composed of 2 lentiviral vectors to be used in a prime/boost regimen in ATLL patients infected by the HTLV-1 virus.
Both investigational drugs encode the same antigens, derived from 4 proteins of the HTLV-1 virus.
THV02 is intended to induce an immune response against HTLV antigens born by ATLL with the aim of enabling the patients’ immune system to fight leukemic cells.
Preclinical evaluation has suggested that THV02 is safe, and the vaccine has presented an “unprecedented” immunogenicity profile in several models, according to THERAVECTYS, the company developing THV02.
“Preclinical immunogenicity results obtained to date are very promising, and we are really excited by the prospect of bringing a safe and better-tolerated alternative to patients who are desperately in need of a treatment,” said Déborah Revaud, the senior scientist in charge of developing THV02.
The EMA grants orphan designation to drugs in development intended for the treatment, prevention, or diagnosis of life-threatening or chronically debilitating diseases occurring in fewer than 5 in 10,000 people.
The designation allows sponsors to benefit from an accelerated development process, financial incentives, and a 10-year period of market exclusivity once the drug is on the market.
“We are extremely pleased that the European Medicines Agency has granted an orphan drug status to our vaccine candidate against ATLL,” said Emmanuelle Sabbah-Petrover, PhD, head of regulatory affairs at THERAVECTYS.
“We expect to recruit our first patients towards the end of Q3 2015 in Europe and advance further developments in the US and in Japan in 2016.”
Should THV02 demonstrate a convincing safety and efficacy profile during its development against ATLL, THERAVECTYS said it will consider developing the vaccine for HTLV-related infections as treatment and possibly as prophylaxis. 
The European Medicines Agency (EMA) has granted orphan drug designation for a therapeutic vaccine candidate known as THV02 to treat adult T-cell leukemia/lymphoma (ATLL).
THV02 is an experimental treatment composed of 2 lentiviral vectors to be used in a prime/boost regimen in ATLL patients infected by the HTLV-1 virus.
Both investigational drugs encode the same antigens, derived from 4 proteins of the HTLV-1 virus.
THV02 is intended to induce an immune response against HTLV antigens born by ATLL with the aim of enabling the patients’ immune system to fight leukemic cells.
Preclinical evaluation has suggested that THV02 is safe, and the vaccine has presented an “unprecedented” immunogenicity profile in several models, according to THERAVECTYS, the company developing THV02.
“Preclinical immunogenicity results obtained to date are very promising, and we are really excited by the prospect of bringing a safe and better-tolerated alternative to patients who are desperately in need of a treatment,” said Déborah Revaud, the senior scientist in charge of developing THV02.
The EMA grants orphan designation to drugs in development intended for the treatment, prevention, or diagnosis of life-threatening or chronically debilitating diseases occurring in fewer than 5 in 10,000 people.
The designation allows sponsors to benefit from an accelerated development process, financial incentives, and a 10-year period of market exclusivity once the drug is on the market.
“We are extremely pleased that the European Medicines Agency has granted an orphan drug status to our vaccine candidate against ATLL,” said Emmanuelle Sabbah-Petrover, PhD, head of regulatory affairs at THERAVECTYS.
“We expect to recruit our first patients towards the end of Q3 2015 in Europe and advance further developments in the US and in Japan in 2016.”
Should THV02 demonstrate a convincing safety and efficacy profile during its development against ATLL, THERAVECTYS said it will consider developing the vaccine for HTLV-related infections as treatment and possibly as prophylaxis.
The European Medicines Agency (EMA) has granted orphan drug designation for a therapeutic vaccine candidate known as THV02 to treat adult T-cell leukemia/lymphoma (ATLL).
THV02 is an experimental treatment composed of 2 lentiviral vectors to be used in a prime/boost regimen in ATLL patients infected by the HTLV-1 virus.
Both investigational drugs encode the same antigens, derived from 4 proteins of the HTLV-1 virus.
THV02 is intended to induce an immune response against HTLV antigens born by ATLL with the aim of enabling the patients’ immune system to fight leukemic cells.
Preclinical evaluation has suggested that THV02 is safe, and the vaccine has presented an “unprecedented” immunogenicity profile in several models, according to THERAVECTYS, the company developing THV02.
“Preclinical immunogenicity results obtained to date are very promising, and we are really excited by the prospect of bringing a safe and better-tolerated alternative to patients who are desperately in need of a treatment,” said Déborah Revaud, the senior scientist in charge of developing THV02.
The EMA grants orphan designation to drugs in development intended for the treatment, prevention, or diagnosis of life-threatening or chronically debilitating diseases occurring in fewer than 5 in 10,000 people.
The designation allows sponsors to benefit from an accelerated development process, financial incentives, and a 10-year period of market exclusivity once the drug is on the market.
“We are extremely pleased that the European Medicines Agency has granted an orphan drug status to our vaccine candidate against ATLL,” said Emmanuelle Sabbah-Petrover, PhD, head of regulatory affairs at THERAVECTYS.
“We expect to recruit our first patients towards the end of Q3 2015 in Europe and advance further developments in the US and in Japan in 2016.”
Should THV02 demonstrate a convincing safety and efficacy profile during its development against ATLL, THERAVECTYS said it will consider developing the vaccine for HTLV-related infections as treatment and possibly as prophylaxis.
Product deemed breakthrough for beta-thalassemia major
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.
The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.
The product is intended to treat sickle cell disease as well as beta-thalassemia major.
“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.
“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”
Early study results
The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.
As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.
Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.
The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
About breakthrough designation
The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.
For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.
The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.
Breakthrough therapy designation does not change the standards for approval.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.
The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.
The product is intended to treat sickle cell disease as well as beta-thalassemia major.
“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.
“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”
Early study results
The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.
As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.
Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.
The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
About breakthrough designation
The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.
For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.
The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.
Breakthrough therapy designation does not change the standards for approval.
The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to LentiGlobin® BB305 for the treatment of transfusion-dependent patients with beta-thalassemia major.
The product is created by inserting a functional human beta-globin gene into a patient’s hematopoietic stem cells ex vivo. The cells are returned to the patient via transplant.
The product is intended to treat sickle cell disease as well as beta-thalassemia major.
“The FDA’s breakthrough designation of LentiGlobin highlights that new therapies are needed for the treatment of patients with beta-thalassemia major, especially treatments with the potential to meaningfully reduce or liberate patients from transfusion dependence,” said David Davidson, MD, chief medical officer of bluebird bio, the company developing LentiGlobin.
“Our early clinical data investigating the use of LentiGlobin in patients with multiple genotypes of beta-thalassemia major . . . are very encouraging, and we remain on track to complete enrollment in the Northstar and HGB-205 studies in 2015.”
Early study results
The breakthrough designation is supported by data from the ongoing phase 1/2 Northstar (HGB-204) and HGB-205 studies. Findings in 8 subjects from both studies were presented at the 2014 ASH Annual Meeting.
As of December 1, five subjects with beta-thalassemia major had received LentiGlobin in the Northstar Study. The first 2 subjects were producing steadily increasing amounts of beta-T87Q-globin and were free of the need for transfusion for 5 months and 3 months, respectively.
Three additional subjects have received LentiGlobin as well, but researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
As of December 1, two subjects with beta-thalassemia major received LentiGlobin as part of the HGB-205 study. Both achieved rapid transfusion independence with near-normal hemoglobin levels. And they were free from the need for transfusions for 12 months and 9 months, respectively.
The third treated subject, the first individual with sickle cell disease ever to be treated with gene therapy, has achieved neutrophil engraftment. But researchers said it is too early to draw any meaningful conclusions on clinical efficacy.
About breakthrough designation
The FDA’s breakthrough therapy designation is intended to expedite the development and review of a drug candidate intended to treat a serious or life-threatening condition.
For a drug to gain the designation, preliminary clinical evidence must suggest the drug could offer substantial improvement over existing therapies on one or more clinically significant endpoints.
The benefits of breakthrough designation include the same benefits as fast track designation (priority review, rolling review, etc.), plus an organizational commitment involving the FDA’s senior managers with more intensive guidance from the FDA.
Breakthrough therapy designation does not change the standards for approval.
NICE gives conditional support for eculizumab
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.
The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.
aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.
The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.
“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.
“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”
The conditions for funding eculizumab are as follows:
- Use of the drug must be coordinated through an expert center.
- Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
- A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
- A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.
Eculizumab usage and costs
Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.
The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).
The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.
If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.
The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).
Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.
For more information, see the guidance on the NICE website.
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.
The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.
aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.
The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.
“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.
“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”
The conditions for funding eculizumab are as follows:
- Use of the drug must be coordinated through an expert center.
- Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
- A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
- A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.
Eculizumab usage and costs
Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.
The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).
The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.
If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.
The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).
Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.
For more information, see the guidance on the NICE website.
Credit: Globovision
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final guidance recommending eculizumab (Soliris) as a treatment for atypical hemolytic uremic syndrome (aHUS), but only if certain conditions are met.
The guidance is the first to be produced as part of NICE’s highly specialized technologies program to evaluate treatments for very rare conditions.
aHUS affects around 200 people in England, with 20 to 30 new patients diagnosed with the condition each year.
The condition causes inflammation of blood vessels and thrombus formation throughout the body. So aHUS patients are at constant risk of sudden and progressive damage to, and failure of, vital organs.
“aHUS is a very distressing condition that imposes a significant burden both on those with the condition and their carers and families,” said NICE Chief Executive Sir Andrew Dillon.
“[A committee advising NICE] accepted that eculizumab is a step change in the management of aHUS and can be considered a significant innovation for a disease with a high unmet clinical need. It offers people with aHUS the possibility of avoiding end-stage renal failure, dialysis, and kidney transplantation, as well as other organ damage.”
“The drug is, however, very expensive. The committee felt that the budget impact of eculizumab would be lower if the potential for adjusting the dose of the drug and stopping treatment was explored. This is reflected in the guidance, which recommends eculizumab should be funded only if important conditions are met, including the development of rules for starting and stopping treatment for clinical reasons. In the meantime, NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS.”
The conditions for funding eculizumab are as follows:
- Use of the drug must be coordinated through an expert center.
- Monitoring systems must record the number of people with aHUS, the number who receive eculizumab, and the dose and duration of treatment.
- A national protocol must be developed for starting and stopping eculizumab for clinical reasons.
- A research program is needed with robust methods to evaluate when stopping treatment or dose adjustment might occur.
Eculizumab usage and costs
Eculizumab is given intravenously in adults as initial treatment at a dose of 900 mg for 4 weeks, then as maintenance treatment at a dose of 1200 mg on week 5 and then every 12 to 16 days.
The summary of product characteristics for eculizumab states that “treatment is recommended to continue for a patient’s lifetime, unless discontinuation of treatment is clinically indicated.” Eculizumab costs £3150 per 30 mL vial (excluding tax).
The net budget impact of eculizumab is confidential. However, NICE has prepared an illustration of the possible budget impact of eculizumab for aHUS, using information that is available in the public domain.
This is based on a treatment cost of £340,200 per adult patient in the first year (based on the acquisition cost of the drug and the recommended dosing for an adult) and assumes a patient cohort of 170, as estimated by NHS England.
If it is assumed that all of these adults with aHUS are treated with eculizumab, the budget impact for the first year would be £57.8 million.
If an additional 20 new patients are treated the following year (based on a worldwide incidence of 0.4 per million), the budget impact will rise to £62.5 million in year 2, assuming all new patients are treated and all existing patients continue to be treated at the maintenance cost of £327,600 per year.
Using the same assumptions, the budget impact will rise to £69 million in year 3 (190 existing and 20 new patients), £75 million in year 4 (210 existing and 20 new patients), and £82 million in year 5 (230 existing and 20 new patients).
NHS England has indicated that the amount of the budget allocated for highly specialized services in 2013/14 was £544 million, and the money spent on high-cost drugs was £156 million.
The committee acknowledged that the estimate of the incremental cost of eculizumab made by Alexion Pharmaceuticals (the company developing eculizumab) compared with standard care was considerable. And incremental costs estimated by the evidence review group were higher still (although results are confidential).
Alexion estimated that eculizumab produced 25.22 additional quality-adjusted life-years (QALYs) per patient compared with standard care. Although the QALYs estimated in the evidence review group’s analysis were markedly lower than those calculated by the company, the advisory committee said both analyses produced substantial QALY gains of a magnitude that is rarely seen for any new drug.
For more information, see the guidance on the NICE website.
FDA approves ibrutinib for WM
Credit: CDC
The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).
The drug is now approved as a single agent for use in all lines of therapy.
This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.
Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.
The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.
The median duration of response has not been reached, with a range of 2.8 to 18.8 months.
The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.
Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.
For more details, see the full prescribing information.
Credit: CDC
The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).
The drug is now approved as a single agent for use in all lines of therapy.
This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.
Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.
The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.
The median duration of response has not been reached, with a range of 2.8 to 18.8 months.
The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.
Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.
For more details, see the full prescribing information.
Credit: CDC
The US Food and Drug Administration (FDA) has granted approval for ibrutinib (Imbruvica) as the first and only treatment for patients with Waldenstrom’s macroglobulinemia (WM).
The drug is now approved as a single agent for use in all lines of therapy.
This is the fourth indication for ibrutinib, which is also FDA-approved to treat patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients with del 17p, and patients with mantle cell lymphoma.
Ibrutinib is being jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc.
The latest FDA approval is based on results from a multicenter, phase 2 study in which researchers evaluated the efficacy and tolerability of ibrutinib in 63 patients with previously treated WM.
The response rate, according to an independent review committee, was 62%. Eleven percent of patients had a very good partial response rate, and 51% had a partial response rate.
The median duration of response has not been reached, with a range of 2.8 to 18.8 months.
The most commonly occurring adverse events (>20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue.
Six percent of patients discontinued treatment due to adverse events. Events leading to dose reduction occurred in 11% of patients.
For more details, see the full prescribing information.
Drug on the fast track to treat HAE
within pancreatic tissue
Credit: Louisa Howard
The US Food and Drug Administration (FDA) has granted fast track designation for BCX4161, an oral inhibitor of plasma kallikrein intended to treat hereditary angioedema (HAE).
Uncontrolled activation of plasma kallikrein, caused by deficiency of its physiological inhibitor (C1 inhibitor) in HAE, results in acute systemic edema.
By inhibiting plasma kallikrein, BCX4161 suppresses the production of bradykinin, the mediator of acute swelling attacks in HAE patients.
HAE is a severely debilitating and potentially fatal condition that occurs in approximately 1 in 50,000 people. Symptoms include recurrent episodes of edema in various locations, as well as bouts of excruciating abdominal pain, nausea, and vomiting that are caused by swelling in the intestinal walls.
HAE patients have a defect in the gene that controls C1 inhibitor, and this results in the production of inadequate or non-functioning C1 inhibitor protein.
Normal C1 inhibitor helps regulate the biochemical interactions of blood-based systems involved in disease-fighting, inflammatory response, and coagulation.
Because defective C1 inhibitor does not adequately perform its regulatory function, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, causing edema.
BCX4161 trials
In May 2014, BioCryst Pharmaceuticals, the company developing BCX4161, announced results from the phase 2a OPuS-1 trial.
OPuS-1 investigators evaluated 400 mg of BCX4161 administered 3 times a day for 28 days in HAE patients with a high angioedema attack frequency (≥ 1 per week), in a randomized, placebo-controlled, 2-period cross-over design.
BCX4161 demonstrated a significant reduction in mean attack rate compared to placebo. The mean attack rate per patient-week was 0.82 on BCX4161 treatment and 1.27 on placebo (P<0.001).
The mean number of attack-free days during each treatment period improved from 19 for placebo to 22 for BCX4161 (P=0.008). Three subjects were attack-free during the BCX4161 period, compared to none during the placebo period.
BCX4161 was generally well-tolerated, BioCryst reported, with an adverse event profile similar to that observed for placebo. There was one serious adverse event reported, an abdominal HAE attack during the placebo period.
In December, the first patient was dosed in the OPuS-2 trial, a double-blind, randomized, placebo- controlled trial conducted in the US and European Union.
Study investigators will evaluate the efficacy and safety of BCX4161 treatment for 12 weeks in patients with HAE. BioCryst expects to report results from OPuS-2 by the end of 2015.
About fast track designation
The FDA’s fast track process is designed to facilitate the development and expedite the review and approval of drugs intended to treat serious or life-threatening conditions that also address unmet medical needs.
A drug that receives fast track designation is usually eligible for more frequent written communication and meetings with the FDA to discuss the drug’s development plan and the collection of appropriate data supporting drug approval.
Priority review and rolling review may be granted if relevant criteria are met. Rolling review allows a drug company to submit completed sections of its new drug application on an ongoing basis, rather than wait until the entire application is complete.
within pancreatic tissue
Credit: Louisa Howard
The US Food and Drug Administration (FDA) has granted fast track designation for BCX4161, an oral inhibitor of plasma kallikrein intended to treat hereditary angioedema (HAE).
Uncontrolled activation of plasma kallikrein, caused by deficiency of its physiological inhibitor (C1 inhibitor) in HAE, results in acute systemic edema.
By inhibiting plasma kallikrein, BCX4161 suppresses the production of bradykinin, the mediator of acute swelling attacks in HAE patients.
HAE is a severely debilitating and potentially fatal condition that occurs in approximately 1 in 50,000 people. Symptoms include recurrent episodes of edema in various locations, as well as bouts of excruciating abdominal pain, nausea, and vomiting that are caused by swelling in the intestinal walls.
HAE patients have a defect in the gene that controls C1 inhibitor, and this results in the production of inadequate or non-functioning C1 inhibitor protein.
Normal C1 inhibitor helps regulate the biochemical interactions of blood-based systems involved in disease-fighting, inflammatory response, and coagulation.
Because defective C1 inhibitor does not adequately perform its regulatory function, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, causing edema.
BCX4161 trials
In May 2014, BioCryst Pharmaceuticals, the company developing BCX4161, announced results from the phase 2a OPuS-1 trial.
OPuS-1 investigators evaluated 400 mg of BCX4161 administered 3 times a day for 28 days in HAE patients with a high angioedema attack frequency (≥ 1 per week), in a randomized, placebo-controlled, 2-period cross-over design.
BCX4161 demonstrated a significant reduction in mean attack rate compared to placebo. The mean attack rate per patient-week was 0.82 on BCX4161 treatment and 1.27 on placebo (P<0.001).
The mean number of attack-free days during each treatment period improved from 19 for placebo to 22 for BCX4161 (P=0.008). Three subjects were attack-free during the BCX4161 period, compared to none during the placebo period.
BCX4161 was generally well-tolerated, BioCryst reported, with an adverse event profile similar to that observed for placebo. There was one serious adverse event reported, an abdominal HAE attack during the placebo period.
In December, the first patient was dosed in the OPuS-2 trial, a double-blind, randomized, placebo- controlled trial conducted in the US and European Union.
Study investigators will evaluate the efficacy and safety of BCX4161 treatment for 12 weeks in patients with HAE. BioCryst expects to report results from OPuS-2 by the end of 2015.
About fast track designation
The FDA’s fast track process is designed to facilitate the development and expedite the review and approval of drugs intended to treat serious or life-threatening conditions that also address unmet medical needs.
A drug that receives fast track designation is usually eligible for more frequent written communication and meetings with the FDA to discuss the drug’s development plan and the collection of appropriate data supporting drug approval.
Priority review and rolling review may be granted if relevant criteria are met. Rolling review allows a drug company to submit completed sections of its new drug application on an ongoing basis, rather than wait until the entire application is complete.
within pancreatic tissue
Credit: Louisa Howard
The US Food and Drug Administration (FDA) has granted fast track designation for BCX4161, an oral inhibitor of plasma kallikrein intended to treat hereditary angioedema (HAE).
Uncontrolled activation of plasma kallikrein, caused by deficiency of its physiological inhibitor (C1 inhibitor) in HAE, results in acute systemic edema.
By inhibiting plasma kallikrein, BCX4161 suppresses the production of bradykinin, the mediator of acute swelling attacks in HAE patients.
HAE is a severely debilitating and potentially fatal condition that occurs in approximately 1 in 50,000 people. Symptoms include recurrent episodes of edema in various locations, as well as bouts of excruciating abdominal pain, nausea, and vomiting that are caused by swelling in the intestinal walls.
HAE patients have a defect in the gene that controls C1 inhibitor, and this results in the production of inadequate or non-functioning C1 inhibitor protein.
Normal C1 inhibitor helps regulate the biochemical interactions of blood-based systems involved in disease-fighting, inflammatory response, and coagulation.
Because defective C1 inhibitor does not adequately perform its regulatory function, a biochemical imbalance can occur and produce unwanted peptides that induce the capillaries to release fluids into surrounding tissue, causing edema.
BCX4161 trials
In May 2014, BioCryst Pharmaceuticals, the company developing BCX4161, announced results from the phase 2a OPuS-1 trial.
OPuS-1 investigators evaluated 400 mg of BCX4161 administered 3 times a day for 28 days in HAE patients with a high angioedema attack frequency (≥ 1 per week), in a randomized, placebo-controlled, 2-period cross-over design.
BCX4161 demonstrated a significant reduction in mean attack rate compared to placebo. The mean attack rate per patient-week was 0.82 on BCX4161 treatment and 1.27 on placebo (P<0.001).
The mean number of attack-free days during each treatment period improved from 19 for placebo to 22 for BCX4161 (P=0.008). Three subjects were attack-free during the BCX4161 period, compared to none during the placebo period.
BCX4161 was generally well-tolerated, BioCryst reported, with an adverse event profile similar to that observed for placebo. There was one serious adverse event reported, an abdominal HAE attack during the placebo period.
In December, the first patient was dosed in the OPuS-2 trial, a double-blind, randomized, placebo- controlled trial conducted in the US and European Union.
Study investigators will evaluate the efficacy and safety of BCX4161 treatment for 12 weeks in patients with HAE. BioCryst expects to report results from OPuS-2 by the end of 2015.
About fast track designation
The FDA’s fast track process is designed to facilitate the development and expedite the review and approval of drugs intended to treat serious or life-threatening conditions that also address unmet medical needs.
A drug that receives fast track designation is usually eligible for more frequent written communication and meetings with the FDA to discuss the drug’s development plan and the collection of appropriate data supporting drug approval.
Priority review and rolling review may be granted if relevant criteria are met. Rolling review allows a drug company to submit completed sections of its new drug application on an ongoing basis, rather than wait until the entire application is complete.
NICE recommends rivaroxaban for ACS
Credit: NHS
In its final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) is recommending rivaroxaban (Xarelto) as an option for preventing adverse outcomes in patients with acute coronary syndromes (ACS).
The agency said it supports use of the factor Xa inhibitor in combination with aspirin and clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the guidance.
“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the draft guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the draft guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”
The final draft guidance is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Cost and clinical effectiveness
An appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
The committee also found rivaroxaban to be cost-effective. According to Bayer Healthcare (the company co-developing rivaroxaban with Janssen Research & Development, LLC), the base-case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base-case estimate was £5622 per QALY gained.
The committee said there is uncertainty about the validity of these results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
Credit: NHS
In its final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) is recommending rivaroxaban (Xarelto) as an option for preventing adverse outcomes in patients with acute coronary syndromes (ACS).
The agency said it supports use of the factor Xa inhibitor in combination with aspirin and clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the guidance.
“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the draft guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the draft guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”
The final draft guidance is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Cost and clinical effectiveness
An appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
The committee also found rivaroxaban to be cost-effective. According to Bayer Healthcare (the company co-developing rivaroxaban with Janssen Research & Development, LLC), the base-case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base-case estimate was £5622 per QALY gained.
The committee said there is uncertainty about the validity of these results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
Credit: NHS
In its final draft guidance, the UK’s National Institute for Health and Care Excellence (NICE) is recommending rivaroxaban (Xarelto) as an option for preventing adverse outcomes in patients with acute coronary syndromes (ACS).
The agency said it supports use of the factor Xa inhibitor in combination with aspirin and clopidogrel or aspirin alone to prevent atherothrombotic events in ACS patients with elevated cardiac biomarkers.
This includes patients who have had ST-segment-elevation myocardial infarctions (STEMIs) or non-ST-segment myocardial infarctions (NSTEMIs) but not unstable angina. In unstable angina, damage to the heart is not severe enough to result in the release of biomarkers into the blood, so this condition is not included in the guidance.
“Because rivaroxaban is associated with a higher risk of causing bleeding than clopidogrel in combination with aspirin or aspirin alone, the draft guidance recommends that, before starting treatment, doctors should carry out a careful assessment of a person’s bleeding risk,” said Carole Longson, NICE Health Technology Evaluation Centre Director.
“The decision to start treatment should be made after an informed discussion between the doctor and patient about the benefits and risks of rivaroxaban. Also, because there is limited experience of treatment with rivaroxaban up to 24 months, the draft guidance recommends careful consideration should be given to whether treatment is continued beyond 12 months.”
The final draft guidance is now with consultees, who have the opportunity to appeal against it. Once NICE issues its final guidance on a technology, it replaces local recommendations.
Cost and clinical effectiveness
An appraisal committee advising NICE concluded that rivaroxaban given at 2.5 mg twice daily in combination with aspirin plus clopidogrel or with aspirin alone was more effective than aspirin plus clopidogrel or aspirin alone for preventing further cardiovascular deaths and myocardial infarction in patients with ACS and raised cardiac biomarkers.
The committee also found rivaroxaban to be cost-effective. According to Bayer Healthcare (the company co-developing rivaroxaban with Janssen Research & Development, LLC), the base-case incremental cost-effectiveness ratio (ICER) was £6203 per quality-adjusted life-year (QALY) gained. The evidence review group’s preferred base-case estimate was £5622 per QALY gained.
The committee said there is uncertainty about the validity of these results, which were based on the ATLAS-ACS 2-TIMI 51 trial, because of the risk of bias resulting from missing trial data and informative censoring.
However, the committee considered that the ICERs presented were all within the range that could be considered cost-effective, and adjusting for the various types of bias that might have occurred was unlikely to increase the ICER to the extent that it would become unacceptable.
The list price of rivaroxaban is £58.88 per 2.5 mg, 56-capsule pack (excluding value-added tax). The license dose is 2.5 mg twice daily, which equates to a price of £2.10 per day.
Assuming a treatment duration of 12 months, total acquisition costs are £766.50. Costs may vary in different settings because of negotiated procurement discounts.
EMA wants to suspend drugs due to data manipulation
Credit: Steven Harbour
The European Medicines Agency (EMA) has recommended suspending a number of drugs that were approved in the European Union (EU) based on clinical studies conducted at GVK Biosciences in Hyderabad, India.
An inspection of the site suggested GVK Bio employees may have manipulated data from trials that took place there.
So the EMA compiled a list of drugs—which includes clopidogrel, dexamethasone, and tacrolimus, among others—that should be suspended.
However, the EMA said there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Bio, and patients should continue taking their medicines as prescribed.
The EMA’s opinion has been forwarded to the European Commission (EC), which will adopt a legally binding decision.
It was at the request of the EC that the EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed the drugs set to be suspended.
An inspection by the French medicines agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM), in May 2014 uncovered “non-compliance with good clinical practice” at the GVK Bio site in Hyderabad.
The ANSM inspector analyzed 9 studies conducted there from 2008 to 2013 and found evidence suggesting that data from electrocardiograms (ECGs) had been manipulated. It appeared that GVK Bio employees were taking multiple ECGs of one volunteer and presenting them as ECGs of other volunteers.
The EMA said the systematic nature of these data manipulations, the extended period of time during which they took place, and the number of staff members involved casts doubt on the integrity of the way trials were performed at the Hyderabad facility and on the reliability of data generated there.
With this in mind, the CHMP looked at more than 1000 pharmaceutical forms and strengths of medicines studied at the site. For more than 300 of the medications, there was sufficient data from other sources to support the drugs’ authorization, so these will remain on the market in the EU.
For drugs that lack data from other studies, the CHMP recommended suspension unless they are of critical importance for patients because alternatives will not be able to meet patients’ needs.
Whether a medicine is critical for patients will be determined by the national authorities of EU member states, depending on the situation in their country. For drugs that are considered critical, companies developing those drugs will be given 12 months to submit additional data.
The CHMP’s recommendation will be sent to the EC for a legally binding decision that will apply to all EU member states whether or not they have taken interim measures to suspend medicines.
GVK Bio responds
GVK Bio said an internal audit conducted following the ANSM inspection suggested that standard operating procedures were followed for the 9 trials analyzed. The organization also sought the opinion of 4 independent cardiologists, who said it was difficult to determine if the ECGs belong to the same volunteer or more than one person.
GVK Bio presented this information to the ANSM, but the agency concluded that the studies did not meet good clinical practice guidelines and should be rejected.
Following subsequent meetings and analyses, the EMA came to a similar conclusion—that the overall findings cast doubt on the results of trials conducted at the Hyderabad facility from 2008 to 2014.
GVK Bio said it respects the EMA’s decision, but their recommended suspension of drugs is “unprecedented and highly disproportional” for a few reasons.
First, the ANSM said the ECGs in question were not essential to demonstrate the bioequivalence of the drugs tested, and the agency’s recommendation to reject the 9 studies was a “precautionary” measure.
The ANSM also said the observations made during the inspection should not be extrapolated to other trial-related activities at the Hyderabad site or GVK Bio’s other site in Ahmedabad.
And finally, the EMA itself said there is no evidence proving that the drugs in question are ineffective or pose a risk to human health.
Credit: Steven Harbour
The European Medicines Agency (EMA) has recommended suspending a number of drugs that were approved in the European Union (EU) based on clinical studies conducted at GVK Biosciences in Hyderabad, India.
An inspection of the site suggested GVK Bio employees may have manipulated data from trials that took place there.
So the EMA compiled a list of drugs—which includes clopidogrel, dexamethasone, and tacrolimus, among others—that should be suspended.
However, the EMA said there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Bio, and patients should continue taking their medicines as prescribed.
The EMA’s opinion has been forwarded to the European Commission (EC), which will adopt a legally binding decision.
It was at the request of the EC that the EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed the drugs set to be suspended.
An inspection by the French medicines agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM), in May 2014 uncovered “non-compliance with good clinical practice” at the GVK Bio site in Hyderabad.
The ANSM inspector analyzed 9 studies conducted there from 2008 to 2013 and found evidence suggesting that data from electrocardiograms (ECGs) had been manipulated. It appeared that GVK Bio employees were taking multiple ECGs of one volunteer and presenting them as ECGs of other volunteers.
The EMA said the systematic nature of these data manipulations, the extended period of time during which they took place, and the number of staff members involved casts doubt on the integrity of the way trials were performed at the Hyderabad facility and on the reliability of data generated there.
With this in mind, the CHMP looked at more than 1000 pharmaceutical forms and strengths of medicines studied at the site. For more than 300 of the medications, there was sufficient data from other sources to support the drugs’ authorization, so these will remain on the market in the EU.
For drugs that lack data from other studies, the CHMP recommended suspension unless they are of critical importance for patients because alternatives will not be able to meet patients’ needs.
Whether a medicine is critical for patients will be determined by the national authorities of EU member states, depending on the situation in their country. For drugs that are considered critical, companies developing those drugs will be given 12 months to submit additional data.
The CHMP’s recommendation will be sent to the EC for a legally binding decision that will apply to all EU member states whether or not they have taken interim measures to suspend medicines.
GVK Bio responds
GVK Bio said an internal audit conducted following the ANSM inspection suggested that standard operating procedures were followed for the 9 trials analyzed. The organization also sought the opinion of 4 independent cardiologists, who said it was difficult to determine if the ECGs belong to the same volunteer or more than one person.
GVK Bio presented this information to the ANSM, but the agency concluded that the studies did not meet good clinical practice guidelines and should be rejected.
Following subsequent meetings and analyses, the EMA came to a similar conclusion—that the overall findings cast doubt on the results of trials conducted at the Hyderabad facility from 2008 to 2014.
GVK Bio said it respects the EMA’s decision, but their recommended suspension of drugs is “unprecedented and highly disproportional” for a few reasons.
First, the ANSM said the ECGs in question were not essential to demonstrate the bioequivalence of the drugs tested, and the agency’s recommendation to reject the 9 studies was a “precautionary” measure.
The ANSM also said the observations made during the inspection should not be extrapolated to other trial-related activities at the Hyderabad site or GVK Bio’s other site in Ahmedabad.
And finally, the EMA itself said there is no evidence proving that the drugs in question are ineffective or pose a risk to human health.
Credit: Steven Harbour
The European Medicines Agency (EMA) has recommended suspending a number of drugs that were approved in the European Union (EU) based on clinical studies conducted at GVK Biosciences in Hyderabad, India.
An inspection of the site suggested GVK Bio employees may have manipulated data from trials that took place there.
So the EMA compiled a list of drugs—which includes clopidogrel, dexamethasone, and tacrolimus, among others—that should be suspended.
However, the EMA said there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Bio, and patients should continue taking their medicines as prescribed.
The EMA’s opinion has been forwarded to the European Commission (EC), which will adopt a legally binding decision.
It was at the request of the EC that the EMA’s Committee for Medicinal Products for Human Use (CHMP) reviewed the drugs set to be suspended.
An inspection by the French medicines agency, Agence nationale de sécurité du médicament et des produits de santé (ANSM), in May 2014 uncovered “non-compliance with good clinical practice” at the GVK Bio site in Hyderabad.
The ANSM inspector analyzed 9 studies conducted there from 2008 to 2013 and found evidence suggesting that data from electrocardiograms (ECGs) had been manipulated. It appeared that GVK Bio employees were taking multiple ECGs of one volunteer and presenting them as ECGs of other volunteers.
The EMA said the systematic nature of these data manipulations, the extended period of time during which they took place, and the number of staff members involved casts doubt on the integrity of the way trials were performed at the Hyderabad facility and on the reliability of data generated there.
With this in mind, the CHMP looked at more than 1000 pharmaceutical forms and strengths of medicines studied at the site. For more than 300 of the medications, there was sufficient data from other sources to support the drugs’ authorization, so these will remain on the market in the EU.
For drugs that lack data from other studies, the CHMP recommended suspension unless they are of critical importance for patients because alternatives will not be able to meet patients’ needs.
Whether a medicine is critical for patients will be determined by the national authorities of EU member states, depending on the situation in their country. For drugs that are considered critical, companies developing those drugs will be given 12 months to submit additional data.
The CHMP’s recommendation will be sent to the EC for a legally binding decision that will apply to all EU member states whether or not they have taken interim measures to suspend medicines.
GVK Bio responds
GVK Bio said an internal audit conducted following the ANSM inspection suggested that standard operating procedures were followed for the 9 trials analyzed. The organization also sought the opinion of 4 independent cardiologists, who said it was difficult to determine if the ECGs belong to the same volunteer or more than one person.
GVK Bio presented this information to the ANSM, but the agency concluded that the studies did not meet good clinical practice guidelines and should be rejected.
Following subsequent meetings and analyses, the EMA came to a similar conclusion—that the overall findings cast doubt on the results of trials conducted at the Hyderabad facility from 2008 to 2014.
GVK Bio said it respects the EMA’s decision, but their recommended suspension of drugs is “unprecedented and highly disproportional” for a few reasons.
First, the ANSM said the ECGs in question were not essential to demonstrate the bioequivalence of the drugs tested, and the agency’s recommendation to reject the 9 studies was a “precautionary” measure.
The ANSM also said the observations made during the inspection should not be extrapolated to other trial-related activities at the Hyderabad site or GVK Bio’s other site in Ahmedabad.
And finally, the EMA itself said there is no evidence proving that the drugs in question are ineffective or pose a risk to human health.
CHMP recommends ruxolitinib for PV
Credit: Zak Hubbard
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending the approval of ruxolitinib (Jakavi) to
treat adults with polycythemia vera (PV) who are resistant to or cannot tolerate hydroxyurea.
The European Commission generally follows the CHMP’s advice and delivers its final decision within 3 months of the CHMP recommendation.
If approved, ruxolitinib would be the first targeted treatment option for PV patients in Europe.
The European Commission’s decision will be applicable to all 28 member states of the European Union, plus Iceland, Norway, and Liechtenstein.
About ruxolitinib
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. It was approved by the European Commission in August 2012 to treat adults with primary myelofibrosis (MF), post-PV MF, or post-essential thrombocythemia MF. The drug is approved to treat MF in more than 70 countries.
Novartis licensed ruxolitinib from Incyte Corporation (which markets the drug as Jakafi in the US) for development and commercialization outside the US. Ruxolitinib is approved in the US to treat patients with MF and those with PV.
Ruxolitinib in PV: The RESPONSE trial
The CHMP’s recommendation to approve ruxolitinib for PV was based on results from the phase 3 RESPONSE trial, which was funded by Incyte.
The trial included 222 patients who had PV for at least 24 weeks. All patients had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy, and had an enlarged spleen.
They were randomized to receive ruxolitinib starting at 10 mg twice daily or best available therapy (BAT) as determined by the investigator. The ruxolitinib dose was adjusted as needed.
The study was designed to measure the reduced need for phlebotomy beginning at week 8 and continuing through week 32, in addition to at least a 35% reduction in spleen volume at week 32.
Twenty-one percent of ruxolitinib-treated patients met this endpoint, compared to 1% of patients who received BAT.
Ruxolitinib was generally well-tolerated, but 3.6% of patients discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
The most common hematologic adverse events associated with ruxolitinib were anemia and thrombocytopenia. The most common non-hematologic events were headache, diarrhea, fatigue, dizziness, constipation, and shingles.
Credit: Zak Hubbard
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending the approval of ruxolitinib (Jakavi) to
treat adults with polycythemia vera (PV) who are resistant to or cannot tolerate hydroxyurea.
The European Commission generally follows the CHMP’s advice and delivers its final decision within 3 months of the CHMP recommendation.
If approved, ruxolitinib would be the first targeted treatment option for PV patients in Europe.
The European Commission’s decision will be applicable to all 28 member states of the European Union, plus Iceland, Norway, and Liechtenstein.
About ruxolitinib
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. It was approved by the European Commission in August 2012 to treat adults with primary myelofibrosis (MF), post-PV MF, or post-essential thrombocythemia MF. The drug is approved to treat MF in more than 70 countries.
Novartis licensed ruxolitinib from Incyte Corporation (which markets the drug as Jakafi in the US) for development and commercialization outside the US. Ruxolitinib is approved in the US to treat patients with MF and those with PV.
Ruxolitinib in PV: The RESPONSE trial
The CHMP’s recommendation to approve ruxolitinib for PV was based on results from the phase 3 RESPONSE trial, which was funded by Incyte.
The trial included 222 patients who had PV for at least 24 weeks. All patients had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy, and had an enlarged spleen.
They were randomized to receive ruxolitinib starting at 10 mg twice daily or best available therapy (BAT) as determined by the investigator. The ruxolitinib dose was adjusted as needed.
The study was designed to measure the reduced need for phlebotomy beginning at week 8 and continuing through week 32, in addition to at least a 35% reduction in spleen volume at week 32.
Twenty-one percent of ruxolitinib-treated patients met this endpoint, compared to 1% of patients who received BAT.
Ruxolitinib was generally well-tolerated, but 3.6% of patients discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
The most common hematologic adverse events associated with ruxolitinib were anemia and thrombocytopenia. The most common non-hematologic events were headache, diarrhea, fatigue, dizziness, constipation, and shingles.
Credit: Zak Hubbard
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending the approval of ruxolitinib (Jakavi) to
treat adults with polycythemia vera (PV) who are resistant to or cannot tolerate hydroxyurea.
The European Commission generally follows the CHMP’s advice and delivers its final decision within 3 months of the CHMP recommendation.
If approved, ruxolitinib would be the first targeted treatment option for PV patients in Europe.
The European Commission’s decision will be applicable to all 28 member states of the European Union, plus Iceland, Norway, and Liechtenstein.
About ruxolitinib
Ruxolitinib is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. It was approved by the European Commission in August 2012 to treat adults with primary myelofibrosis (MF), post-PV MF, or post-essential thrombocythemia MF. The drug is approved to treat MF in more than 70 countries.
Novartis licensed ruxolitinib from Incyte Corporation (which markets the drug as Jakafi in the US) for development and commercialization outside the US. Ruxolitinib is approved in the US to treat patients with MF and those with PV.
Ruxolitinib in PV: The RESPONSE trial
The CHMP’s recommendation to approve ruxolitinib for PV was based on results from the phase 3 RESPONSE trial, which was funded by Incyte.
The trial included 222 patients who had PV for at least 24 weeks. All patients had an inadequate response to or could not tolerate hydroxyurea, had undergone a phlebotomy, and had an enlarged spleen.
They were randomized to receive ruxolitinib starting at 10 mg twice daily or best available therapy (BAT) as determined by the investigator. The ruxolitinib dose was adjusted as needed.
The study was designed to measure the reduced need for phlebotomy beginning at week 8 and continuing through week 32, in addition to at least a 35% reduction in spleen volume at week 32.
Twenty-one percent of ruxolitinib-treated patients met this endpoint, compared to 1% of patients who received BAT.
Ruxolitinib was generally well-tolerated, but 3.6% of patients discontinued treatment due to adverse events, compared to 1.8% of patients on BAT.
The most common hematologic adverse events associated with ruxolitinib were anemia and thrombocytopenia. The most common non-hematologic events were headache, diarrhea, fatigue, dizziness, constipation, and shingles.
FDA puts drug on fast track to treat secondary AML
The US Food and Drug Administration (FDA) has granted fast track designation for CPX-351, a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat elderly patients with secondary acute myeloid leukemia (AML).
In a phase 2 study of elderly AML patients, there was no significant difference in response or survival rates between patients who received CPX-351 and those who received cytarabine and daunorubicin.
However, CPX-351 conferred a significant response benefit among patients with poor cytogenetics and a significant survival benefit in patients with secondary AML.
“We are pleased that FDA has granted fast track status for CPX-351 for the treatment of elderly patients with secondary AML,” said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals, the company developing CPX-351.
“Our ongoing phase 3 study in these patients has completed enrollment, and we expect induction response rate data to be available in the second quarter of this year, and to have overall survival data, the primary endpoint of the study, in the first quarter of 2016.”
“If our phase 3 study comparing CPX-351 to the current standard of care is successful, the fast track designation may provide an added benefit of facilitating the [new drug application] review process.”
The FDA established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.
Phase 2 trial
In an article published in Blood last April, researchers reported results with CPX-351 in elderly patients with newly diagnosed AML. The study enrolled 126 patients who were 60 to 75 years of age.
They were randomized to receive CPX-351 (n=85) or “control” treatment consisting of cytarabine and daunorubicin (n=41). The treatment groups were well-balanced for disease and patient characteristics at baseline.
Overall, the response rate was 66.7% in the CPX-351 arm and 51.2% in the control arm (P=0.07). Among patients with adverse cytogenetics, the response rates were 77.3% and 38.5%, respectively (P=0.03). And among patients with secondary AML, response rates were 57.6% and 31.6%, respectively (P=0.06).
The median overall survival was 14.7 months in the CPX-351 arm and 12.9 months in the control arm. The median event-free survival was 6.5 months and 2.0 months, respectively. These differences were not statistically significant.
However, secondary AML patients treated with CPX-351 had significantly better overall survival than secondary AML patients in the control arm. The median overall survival was 12.1 months and 6.1 months, respectively (P=0.01). The median event-free survival was 4.5 months and 1.3 months, respectively (P=0.08).
Common adverse events included febrile neutropenia, infection, rash, diarrhea, nausea, edema, and constipation. There were minimal differences between the treatment arms in the incidence of these events.
The median time to neutrophil recovery was longer in the CPX-351 arm than in the control arm—36 days and 32 days, respectively. And the same was true for platelet recovery—37 days and 28 days, respectively.
Patients in the CPX-351 arm had a higher incidence of grade 3-4 infection than controls—70.6% and 43.9%, respectively—but not infection-related deaths—3.5% and 7.3%, respectively.
By day 60, 4.7% of patients in the CPX-351 arm and 14.6% of patients in the control arm had died. All of these deaths occurred in high-risk patients, particularly those with secondary AML.
The US Food and Drug Administration (FDA) has granted fast track designation for CPX-351, a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat elderly patients with secondary acute myeloid leukemia (AML).
In a phase 2 study of elderly AML patients, there was no significant difference in response or survival rates between patients who received CPX-351 and those who received cytarabine and daunorubicin.
However, CPX-351 conferred a significant response benefit among patients with poor cytogenetics and a significant survival benefit in patients with secondary AML.
“We are pleased that FDA has granted fast track status for CPX-351 for the treatment of elderly patients with secondary AML,” said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals, the company developing CPX-351.
“Our ongoing phase 3 study in these patients has completed enrollment, and we expect induction response rate data to be available in the second quarter of this year, and to have overall survival data, the primary endpoint of the study, in the first quarter of 2016.”
“If our phase 3 study comparing CPX-351 to the current standard of care is successful, the fast track designation may provide an added benefit of facilitating the [new drug application] review process.”
The FDA established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.
Phase 2 trial
In an article published in Blood last April, researchers reported results with CPX-351 in elderly patients with newly diagnosed AML. The study enrolled 126 patients who were 60 to 75 years of age.
They were randomized to receive CPX-351 (n=85) or “control” treatment consisting of cytarabine and daunorubicin (n=41). The treatment groups were well-balanced for disease and patient characteristics at baseline.
Overall, the response rate was 66.7% in the CPX-351 arm and 51.2% in the control arm (P=0.07). Among patients with adverse cytogenetics, the response rates were 77.3% and 38.5%, respectively (P=0.03). And among patients with secondary AML, response rates were 57.6% and 31.6%, respectively (P=0.06).
The median overall survival was 14.7 months in the CPX-351 arm and 12.9 months in the control arm. The median event-free survival was 6.5 months and 2.0 months, respectively. These differences were not statistically significant.
However, secondary AML patients treated with CPX-351 had significantly better overall survival than secondary AML patients in the control arm. The median overall survival was 12.1 months and 6.1 months, respectively (P=0.01). The median event-free survival was 4.5 months and 1.3 months, respectively (P=0.08).
Common adverse events included febrile neutropenia, infection, rash, diarrhea, nausea, edema, and constipation. There were minimal differences between the treatment arms in the incidence of these events.
The median time to neutrophil recovery was longer in the CPX-351 arm than in the control arm—36 days and 32 days, respectively. And the same was true for platelet recovery—37 days and 28 days, respectively.
Patients in the CPX-351 arm had a higher incidence of grade 3-4 infection than controls—70.6% and 43.9%, respectively—but not infection-related deaths—3.5% and 7.3%, respectively.
By day 60, 4.7% of patients in the CPX-351 arm and 14.6% of patients in the control arm had died. All of these deaths occurred in high-risk patients, particularly those with secondary AML.
The US Food and Drug Administration (FDA) has granted fast track designation for CPX-351, a fixed-ratio combination of cytarabine and daunorubicin inside a lipid vesicle, to treat elderly patients with secondary acute myeloid leukemia (AML).
In a phase 2 study of elderly AML patients, there was no significant difference in response or survival rates between patients who received CPX-351 and those who received cytarabine and daunorubicin.
However, CPX-351 conferred a significant response benefit among patients with poor cytogenetics and a significant survival benefit in patients with secondary AML.
“We are pleased that FDA has granted fast track status for CPX-351 for the treatment of elderly patients with secondary AML,” said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals, the company developing CPX-351.
“Our ongoing phase 3 study in these patients has completed enrollment, and we expect induction response rate data to be available in the second quarter of this year, and to have overall survival data, the primary endpoint of the study, in the first quarter of 2016.”
“If our phase 3 study comparing CPX-351 to the current standard of care is successful, the fast track designation may provide an added benefit of facilitating the [new drug application] review process.”
The FDA established the fast track designation process to expedite the review of drugs that are intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs.
The designation allows a drug’s developer to submit sections of a new drug application (NDA) on a rolling basis, so the FDA can review portions of the NDA as they are received instead of waiting for the entire NDA submission. A fast-track-designated product could be eligible for priority review if supported by clinical data at the time of NDA submission.
Phase 2 trial
In an article published in Blood last April, researchers reported results with CPX-351 in elderly patients with newly diagnosed AML. The study enrolled 126 patients who were 60 to 75 years of age.
They were randomized to receive CPX-351 (n=85) or “control” treatment consisting of cytarabine and daunorubicin (n=41). The treatment groups were well-balanced for disease and patient characteristics at baseline.
Overall, the response rate was 66.7% in the CPX-351 arm and 51.2% in the control arm (P=0.07). Among patients with adverse cytogenetics, the response rates were 77.3% and 38.5%, respectively (P=0.03). And among patients with secondary AML, response rates were 57.6% and 31.6%, respectively (P=0.06).
The median overall survival was 14.7 months in the CPX-351 arm and 12.9 months in the control arm. The median event-free survival was 6.5 months and 2.0 months, respectively. These differences were not statistically significant.
However, secondary AML patients treated with CPX-351 had significantly better overall survival than secondary AML patients in the control arm. The median overall survival was 12.1 months and 6.1 months, respectively (P=0.01). The median event-free survival was 4.5 months and 1.3 months, respectively (P=0.08).
Common adverse events included febrile neutropenia, infection, rash, diarrhea, nausea, edema, and constipation. There were minimal differences between the treatment arms in the incidence of these events.
The median time to neutrophil recovery was longer in the CPX-351 arm than in the control arm—36 days and 32 days, respectively. And the same was true for platelet recovery—37 days and 28 days, respectively.
Patients in the CPX-351 arm had a higher incidence of grade 3-4 infection than controls—70.6% and 43.9%, respectively—but not infection-related deaths—3.5% and 7.3%, respectively.
By day 60, 4.7% of patients in the CPX-351 arm and 14.6% of patients in the control arm had died. All of these deaths occurred in high-risk patients, particularly those with secondary AML.
EC supports continued use of ponatinib
Credit: Rhoda Baer
The European Commission (EC) has concluded that ponatinib (Iclusig) should continue to be prescribed in accordance with its already approved indications.
After trial results suggested the drug poses an increased risk of thrombotic events, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) conducted a review of available ponatinib data.
Results of that review suggested the benefits of ponatinib outweigh the risks. So the committee said the drug should be prescribed as indicated.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recently endorsed this recommendation, and, now, the EC has followed suit. The EC’s decision is legally binding.
Ponatinib is approved in the European Union to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
In October 2013, extended follow-up data from the PACE trial revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Soon after, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events.
The EMA also revised its recommendations for ponatinib—discouraging use of the drug in certain patients, providing advice for managing comorbidities, and suggesting patient monitoring—but kept the drug on the market.
In October 2014, the PRAC concluded its 11-month review of ponatinib data, confirming that the benefit-risk profile of the drug was favorable in its approved indications and recommending that the indications remain unchanged.
However, the PRAC also said the risk of vascular occlusive events with ponatinib is likely dose-related. So the committee recommended that healthcare professionals monitor ponatinib-treated patients and consider dose reductions or discontinuing the drug in certain patients.
The CHMP endorsed these recommendations, and, now, the EC has as well. This is a legally binding decision for ponatinib to continue to be prescribed in Europe in accordance with its already approved indications.
Ponatinib is being developed by ARIAD Pharmaceuticals, Inc.
Credit: Rhoda Baer
The European Commission (EC) has concluded that ponatinib (Iclusig) should continue to be prescribed in accordance with its already approved indications.
After trial results suggested the drug poses an increased risk of thrombotic events, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) conducted a review of available ponatinib data.
Results of that review suggested the benefits of ponatinib outweigh the risks. So the committee said the drug should be prescribed as indicated.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recently endorsed this recommendation, and, now, the EC has followed suit. The EC’s decision is legally binding.
Ponatinib is approved in the European Union to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
In October 2013, extended follow-up data from the PACE trial revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Soon after, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events.
The EMA also revised its recommendations for ponatinib—discouraging use of the drug in certain patients, providing advice for managing comorbidities, and suggesting patient monitoring—but kept the drug on the market.
In October 2014, the PRAC concluded its 11-month review of ponatinib data, confirming that the benefit-risk profile of the drug was favorable in its approved indications and recommending that the indications remain unchanged.
However, the PRAC also said the risk of vascular occlusive events with ponatinib is likely dose-related. So the committee recommended that healthcare professionals monitor ponatinib-treated patients and consider dose reductions or discontinuing the drug in certain patients.
The CHMP endorsed these recommendations, and, now, the EC has as well. This is a legally binding decision for ponatinib to continue to be prescribed in Europe in accordance with its already approved indications.
Ponatinib is being developed by ARIAD Pharmaceuticals, Inc.
Credit: Rhoda Baer
The European Commission (EC) has concluded that ponatinib (Iclusig) should continue to be prescribed in accordance with its already approved indications.
After trial results suggested the drug poses an increased risk of thrombotic events, the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) conducted a review of available ponatinib data.
Results of that review suggested the benefits of ponatinib outweigh the risks. So the committee said the drug should be prescribed as indicated.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recently endorsed this recommendation, and, now, the EC has followed suit. The EC’s decision is legally binding.
Ponatinib is approved in the European Union to treat adults with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia who are resistant to dasatinib or nilotinib, who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
The drug is also approved to treat adults with Philadelphia-chromosome positive acute lymphoblastic leukemia who are resistant to dasatinib, who cannot tolerate dasatinib and subsequent treatment with imatinib is not clinically appropriate, or who have the T315I mutation.
In October 2013, extended follow-up data from the PACE trial revealed that ponatinib-treated patients had a higher incidence of arterial and venous thrombotic events than was observed when the drug first gained approval. So one ponatinib trial was discontinued, and the rest were placed on partial clinical hold.
Soon after, ponatinib was pulled from the US market. The drug ultimately returned to the marketplace with new recommendations designed to decrease the risk of thrombotic events.
The EMA also revised its recommendations for ponatinib—discouraging use of the drug in certain patients, providing advice for managing comorbidities, and suggesting patient monitoring—but kept the drug on the market.
In October 2014, the PRAC concluded its 11-month review of ponatinib data, confirming that the benefit-risk profile of the drug was favorable in its approved indications and recommending that the indications remain unchanged.
However, the PRAC also said the risk of vascular occlusive events with ponatinib is likely dose-related. So the committee recommended that healthcare professionals monitor ponatinib-treated patients and consider dose reductions or discontinuing the drug in certain patients.
The CHMP endorsed these recommendations, and, now, the EC has as well. This is a legally binding decision for ponatinib to continue to be prescribed in Europe in accordance with its already approved indications.
Ponatinib is being developed by ARIAD Pharmaceuticals, Inc.