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COMP recommends orphan designations for KTE-C19
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has adopted positive opinions recommending orphan designation for KTE-C19 to treat acute lymphoblastic leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma.
KTE-C19 is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, a protein expressed on the surface of B cells.
The CAR T-cell therapy already has orphan designation for the treatment of diffuse large B-cell lymphoma in the US and the European Union (EU).
KTE-C19 also has COMP positive opinions for orphan designation in the EU for primary mediastinal B-cell lymphoma and mantle cell lymphoma.
About orphan designation
The COMP adopts an opinion on the granting of orphan designation, and that opinion is submitted to the European Commission for endorsement.
In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.
Companies that obtain orphan designation for a drug benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is approved. Fee reductions are also available, depending on the status of the sponsor and the type of service required.
KTE-C19 research
Last year, researchers reported results with KTE-C19 in the Journal of Clinical Oncology. The study included 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of the CAR T-cell therapy. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with chemotherapy-refractory diffuse large B-cell lymphoma, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Of the 4 patients with chronic lymphocytic leukemia, 3 had a CR, and 1 had a PR. Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR.
KTE-C19 was associated with fever, low blood pressure, focal neurological deficits, and delirium. Toxicities largely occurred in the first 2 weeks after infusion.
All but 2 patients experienced grade 3/4 adverse events. Four patients had grade 3/4 hypotension.
All patients had elevations in serum interferon gamma and/or interleukin 6 around the time of peak toxicity, but most did not develop elevations in serum tumor necrosis factor.
Neurologic toxicities included confusion and obtundation, which have been reported in previous studies. However, 3 patients developed unexpected neurologic abnormalities.
KTE-C19 is currently under investigation in a phase 1/2 trial (ZUMA-1) of patients with refractory, aggressive non-Hodgkin lymphomas. Kite Pharma, Inc., the company developing KTE-C19, plans to present top-line phase 1 data at the 2015 ASH Annual Meeting. 
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has adopted positive opinions recommending orphan designation for KTE-C19 to treat acute lymphoblastic leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma.
KTE-C19 is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, a protein expressed on the surface of B cells.
The CAR T-cell therapy already has orphan designation for the treatment of diffuse large B-cell lymphoma in the US and the European Union (EU).
KTE-C19 also has COMP positive opinions for orphan designation in the EU for primary mediastinal B-cell lymphoma and mantle cell lymphoma.
About orphan designation
The COMP adopts an opinion on the granting of orphan designation, and that opinion is submitted to the European Commission for endorsement.
In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.
Companies that obtain orphan designation for a drug benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is approved. Fee reductions are also available, depending on the status of the sponsor and the type of service required.
KTE-C19 research
Last year, researchers reported results with KTE-C19 in the Journal of Clinical Oncology. The study included 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of the CAR T-cell therapy. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with chemotherapy-refractory diffuse large B-cell lymphoma, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Of the 4 patients with chronic lymphocytic leukemia, 3 had a CR, and 1 had a PR. Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR.
KTE-C19 was associated with fever, low blood pressure, focal neurological deficits, and delirium. Toxicities largely occurred in the first 2 weeks after infusion.
All but 2 patients experienced grade 3/4 adverse events. Four patients had grade 3/4 hypotension.
All patients had elevations in serum interferon gamma and/or interleukin 6 around the time of peak toxicity, but most did not develop elevations in serum tumor necrosis factor.
Neurologic toxicities included confusion and obtundation, which have been reported in previous studies. However, 3 patients developed unexpected neurologic abnormalities.
KTE-C19 is currently under investigation in a phase 1/2 trial (ZUMA-1) of patients with refractory, aggressive non-Hodgkin lymphomas. Kite Pharma, Inc., the company developing KTE-C19, plans to present top-line phase 1 data at the 2015 ASH Annual Meeting.
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has adopted positive opinions recommending orphan designation for KTE-C19 to treat acute lymphoblastic leukemia, chronic lymphocytic leukemia/small lymphocytic lymphoma, and follicular lymphoma.
KTE-C19 is an investigational chimeric antigen receptor (CAR) T-cell therapy designed to target CD19, a protein expressed on the surface of B cells.
The CAR T-cell therapy already has orphan designation for the treatment of diffuse large B-cell lymphoma in the US and the European Union (EU).
KTE-C19 also has COMP positive opinions for orphan designation in the EU for primary mediastinal B-cell lymphoma and mantle cell lymphoma.
About orphan designation
The COMP adopts an opinion on the granting of orphan designation, and that opinion is submitted to the European Commission for endorsement.
In the EU, orphan designation is granted to therapies intended to treat a life-threatening or chronically debilitating condition that affects no more than 5 in 10,000 persons and where no satisfactory treatment is available.
Companies that obtain orphan designation for a drug benefit from a number of incentives, including protocol assistance, a type of scientific advice specific for designated orphan medicines, and 10 years of market exclusivity once the medicine is approved. Fee reductions are also available, depending on the status of the sponsor and the type of service required.
KTE-C19 research
Last year, researchers reported results with KTE-C19 in the Journal of Clinical Oncology. The study included 15 patients with advanced B-cell malignancies.
The patients received a conditioning regimen of cyclophosphamide and fludarabine, followed 1 day later by a single infusion of the CAR T-cell therapy. The researchers noted that the conditioning regimen is known to be active against B-cell malignancies and could have made a direct contribution to patient responses.
Thirteen patients were evaluable for response. Eight patients achieved a complete response (CR), and 4 had a partial response (PR).
Of the 7 patients with chemotherapy-refractory diffuse large B-cell lymphoma, 4 achieved a CR, 2 achieved a PR, and 1 had stable disease. Of the 4 patients with chronic lymphocytic leukemia, 3 had a CR, and 1 had a PR. Among the 2 patients with indolent lymphomas, 1 achieved a CR, and 1 had a PR.
KTE-C19 was associated with fever, low blood pressure, focal neurological deficits, and delirium. Toxicities largely occurred in the first 2 weeks after infusion.
All but 2 patients experienced grade 3/4 adverse events. Four patients had grade 3/4 hypotension.
All patients had elevations in serum interferon gamma and/or interleukin 6 around the time of peak toxicity, but most did not develop elevations in serum tumor necrosis factor.
Neurologic toxicities included confusion and obtundation, which have been reported in previous studies. However, 3 patients developed unexpected neurologic abnormalities.
KTE-C19 is currently under investigation in a phase 1/2 trial (ZUMA-1) of patients with refractory, aggressive non-Hodgkin lymphomas. Kite Pharma, Inc., the company developing KTE-C19, plans to present top-line phase 1 data at the 2015 ASH Annual Meeting.
Watchdog condemns FDA oversight of dabigatran
The US Food and Drug Administration’s (FDA’s) oversight of the oral anticoagulant dabigatran (Pradaxa) raises questions about the agency’s reliability, according to a report by the Project On Government Oversight (POGO).
POGO’s report describes a series of “questionable” calls the FDA has made in its oversight of dabigatran.
The report calls attention to issues with the clinical trial used to support dabigatran’s approval.
It also details concerns regarding FDA advisory committee members, the distribution of potentially misleading information about dabigatran, the possibility that patients receiving dabigatran may actually need to be monitored, and other issues.
“The deeply disturbing part is that the public has to trust the FDA to keep it safe, and the way the agency handled Pradaxa doesn’t inspire confidence,” said Daniel Brian, POGO’s executive director.
This is not the first time the safety of dabigatran and results of dabigatran trials have been called into question.
Following post-marketing reports of adverse events and deaths related to dabigatran, the FDA conducted its own studies investigating the drug’s safety. The agency ultimately concluded that dabigatran’s benefits outweigh any detriments.
Still, a paper published in JAMA in 2012 suggested the FDA may have approved dabigatran too soon.
And several papers published in The BMJ last year indicated that Boehringer Ingelheim, the company developing dabigatran, underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.
The company has denied these allegations, but POGO’s report appears to support these claims, in addition to raising other concerns.
Trial issues
Dabigatran was initially approved by the FDA in 2010 on the basis of the RE-LY trial, in which researchers compared dabigatran and warfarin.
POGO’s report notes that this was an unblinded trial and suggests that investigators treated patients in the dabigatran arm differently than those in the warfarin arm. An FDA review showed that, when study subjects showed “signs of trouble,” those in the dabigatran arm were more likely to stop receiving treatment. This may have prevented adverse events such as hemorrhagic strokes.
FDA inspections also revealed that RE-LY investigators mismanaged parts of the trial. For example, they enrolled patients who were supposed to be excluded and failed to promptly inform Boehringer Ingelheim about possible adverse effects of dabigatran, among other infractions.
POGO’s report also cites FDA documents showing that the agency allowed Boehringer Ingelheim to finalize the scoring system for the RE-LY trial after it was over and the data had been gathered. A subsequent FDA review suggested that this allowance worked in dabigatran’s favor.
Advisory committee concerns
POGO’s report points out that members of the committee that advised the FDA on dabigatran’s approval have financial ties to the drug’s maker.
According to public databases, 2 of the advisory committee members who voted to approve dabigatran went on to receive tens of thousands of dollars from Boehringer Ingelheim.
POGO also found that when Boehringer Ingelheim held a practice session to prepare for questioning by the FDA advisory committee, a former member and a former chairman of that committee were paid to play roles in the rehearsal.
‘Misleading’ information
Another of POGO’s concerns is that the FDA redacted information from a public memo announcing and explaining its decision to approve dabigatran. The deleted section said that patients who were well-treated using warfarin had no reason to switch to dabigatran.
POGO’s report also points out that the FDA initially refused to allow Boehringer Ingelheim to claim that dabigatran was superior to warfarin but later changed its mind without providing much explanation.
In addition, the FDA allowed Boehringer Ingelheim to advertise that, in a clinical trial, dabigatran “reduced stroke risk 35% more than warfarin.” But after dabigatran had been on the market for more than 2.5 years, the FDA decided this claim was misleading.
The agency told Boehringer Ingelheim to add the following clarification: “That means that, in a large clinical study, 3.4% of patients taking warfarin had a stroke, compared to 2.2% of patients taking Pradaxa.” So, in absolute terms, the difference between the drugs was 1.2%.
Potential need for monitoring
According to POGO, Boehringer Ingelheim has been the target of thousands of lawsuits regarding adverse events and deaths thought to be related to dabigatran. In 2013, Boehringer Ingelheim was fined by a federal judge for withholding or failing to preserve records.
Some of these documents suggested that patients taking dabigatran may require monitoring to ensure they remain within a therapeutic range. A scientist at Boehringer Ingelheim, Thorsten Lehr, drafted a paper concluding that there is a therapeutic range for dabigatran.
But company emails indicated that other employees were against publishing this paper. An email from Boehringer Ingelheim’s Jutta Heinrich-Nols said publishing the paper would “make any defense of no monitoring . . . extremely difficult . . . and undermine our efforts to compete” with other new anticoagulants.
For more details, see POGO’s full report. POGO is a nonpartisan, independent watchdog that champions government reform.
The US Food and Drug Administration’s (FDA’s) oversight of the oral anticoagulant dabigatran (Pradaxa) raises questions about the agency’s reliability, according to a report by the Project On Government Oversight (POGO).
POGO’s report describes a series of “questionable” calls the FDA has made in its oversight of dabigatran.
The report calls attention to issues with the clinical trial used to support dabigatran’s approval.
It also details concerns regarding FDA advisory committee members, the distribution of potentially misleading information about dabigatran, the possibility that patients receiving dabigatran may actually need to be monitored, and other issues.
“The deeply disturbing part is that the public has to trust the FDA to keep it safe, and the way the agency handled Pradaxa doesn’t inspire confidence,” said Daniel Brian, POGO’s executive director.
This is not the first time the safety of dabigatran and results of dabigatran trials have been called into question.
Following post-marketing reports of adverse events and deaths related to dabigatran, the FDA conducted its own studies investigating the drug’s safety. The agency ultimately concluded that dabigatran’s benefits outweigh any detriments.
Still, a paper published in JAMA in 2012 suggested the FDA may have approved dabigatran too soon.
And several papers published in The BMJ last year indicated that Boehringer Ingelheim, the company developing dabigatran, underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.
The company has denied these allegations, but POGO’s report appears to support these claims, in addition to raising other concerns.
Trial issues
Dabigatran was initially approved by the FDA in 2010 on the basis of the RE-LY trial, in which researchers compared dabigatran and warfarin.
POGO’s report notes that this was an unblinded trial and suggests that investigators treated patients in the dabigatran arm differently than those in the warfarin arm. An FDA review showed that, when study subjects showed “signs of trouble,” those in the dabigatran arm were more likely to stop receiving treatment. This may have prevented adverse events such as hemorrhagic strokes.
FDA inspections also revealed that RE-LY investigators mismanaged parts of the trial. For example, they enrolled patients who were supposed to be excluded and failed to promptly inform Boehringer Ingelheim about possible adverse effects of dabigatran, among other infractions.
POGO’s report also cites FDA documents showing that the agency allowed Boehringer Ingelheim to finalize the scoring system for the RE-LY trial after it was over and the data had been gathered. A subsequent FDA review suggested that this allowance worked in dabigatran’s favor.
Advisory committee concerns
POGO’s report points out that members of the committee that advised the FDA on dabigatran’s approval have financial ties to the drug’s maker.
According to public databases, 2 of the advisory committee members who voted to approve dabigatran went on to receive tens of thousands of dollars from Boehringer Ingelheim.
POGO also found that when Boehringer Ingelheim held a practice session to prepare for questioning by the FDA advisory committee, a former member and a former chairman of that committee were paid to play roles in the rehearsal.
‘Misleading’ information
Another of POGO’s concerns is that the FDA redacted information from a public memo announcing and explaining its decision to approve dabigatran. The deleted section said that patients who were well-treated using warfarin had no reason to switch to dabigatran.
POGO’s report also points out that the FDA initially refused to allow Boehringer Ingelheim to claim that dabigatran was superior to warfarin but later changed its mind without providing much explanation.
In addition, the FDA allowed Boehringer Ingelheim to advertise that, in a clinical trial, dabigatran “reduced stroke risk 35% more than warfarin.” But after dabigatran had been on the market for more than 2.5 years, the FDA decided this claim was misleading.
The agency told Boehringer Ingelheim to add the following clarification: “That means that, in a large clinical study, 3.4% of patients taking warfarin had a stroke, compared to 2.2% of patients taking Pradaxa.” So, in absolute terms, the difference between the drugs was 1.2%.
Potential need for monitoring
According to POGO, Boehringer Ingelheim has been the target of thousands of lawsuits regarding adverse events and deaths thought to be related to dabigatran. In 2013, Boehringer Ingelheim was fined by a federal judge for withholding or failing to preserve records.
Some of these documents suggested that patients taking dabigatran may require monitoring to ensure they remain within a therapeutic range. A scientist at Boehringer Ingelheim, Thorsten Lehr, drafted a paper concluding that there is a therapeutic range for dabigatran.
But company emails indicated that other employees were against publishing this paper. An email from Boehringer Ingelheim’s Jutta Heinrich-Nols said publishing the paper would “make any defense of no monitoring . . . extremely difficult . . . and undermine our efforts to compete” with other new anticoagulants.
For more details, see POGO’s full report. POGO is a nonpartisan, independent watchdog that champions government reform.
The US Food and Drug Administration’s (FDA’s) oversight of the oral anticoagulant dabigatran (Pradaxa) raises questions about the agency’s reliability, according to a report by the Project On Government Oversight (POGO).
POGO’s report describes a series of “questionable” calls the FDA has made in its oversight of dabigatran.
The report calls attention to issues with the clinical trial used to support dabigatran’s approval.
It also details concerns regarding FDA advisory committee members, the distribution of potentially misleading information about dabigatran, the possibility that patients receiving dabigatran may actually need to be monitored, and other issues.
“The deeply disturbing part is that the public has to trust the FDA to keep it safe, and the way the agency handled Pradaxa doesn’t inspire confidence,” said Daniel Brian, POGO’s executive director.
This is not the first time the safety of dabigatran and results of dabigatran trials have been called into question.
Following post-marketing reports of adverse events and deaths related to dabigatran, the FDA conducted its own studies investigating the drug’s safety. The agency ultimately concluded that dabigatran’s benefits outweigh any detriments.
Still, a paper published in JAMA in 2012 suggested the FDA may have approved dabigatran too soon.
And several papers published in The BMJ last year indicated that Boehringer Ingelheim, the company developing dabigatran, underreported events associated with the drug and withheld data showing that monitoring and dose adjustment could improve the safety of dabigatran without compromising its efficacy.
The company has denied these allegations, but POGO’s report appears to support these claims, in addition to raising other concerns.
Trial issues
Dabigatran was initially approved by the FDA in 2010 on the basis of the RE-LY trial, in which researchers compared dabigatran and warfarin.
POGO’s report notes that this was an unblinded trial and suggests that investigators treated patients in the dabigatran arm differently than those in the warfarin arm. An FDA review showed that, when study subjects showed “signs of trouble,” those in the dabigatran arm were more likely to stop receiving treatment. This may have prevented adverse events such as hemorrhagic strokes.
FDA inspections also revealed that RE-LY investigators mismanaged parts of the trial. For example, they enrolled patients who were supposed to be excluded and failed to promptly inform Boehringer Ingelheim about possible adverse effects of dabigatran, among other infractions.
POGO’s report also cites FDA documents showing that the agency allowed Boehringer Ingelheim to finalize the scoring system for the RE-LY trial after it was over and the data had been gathered. A subsequent FDA review suggested that this allowance worked in dabigatran’s favor.
Advisory committee concerns
POGO’s report points out that members of the committee that advised the FDA on dabigatran’s approval have financial ties to the drug’s maker.
According to public databases, 2 of the advisory committee members who voted to approve dabigatran went on to receive tens of thousands of dollars from Boehringer Ingelheim.
POGO also found that when Boehringer Ingelheim held a practice session to prepare for questioning by the FDA advisory committee, a former member and a former chairman of that committee were paid to play roles in the rehearsal.
‘Misleading’ information
Another of POGO’s concerns is that the FDA redacted information from a public memo announcing and explaining its decision to approve dabigatran. The deleted section said that patients who were well-treated using warfarin had no reason to switch to dabigatran.
POGO’s report also points out that the FDA initially refused to allow Boehringer Ingelheim to claim that dabigatran was superior to warfarin but later changed its mind without providing much explanation.
In addition, the FDA allowed Boehringer Ingelheim to advertise that, in a clinical trial, dabigatran “reduced stroke risk 35% more than warfarin.” But after dabigatran had been on the market for more than 2.5 years, the FDA decided this claim was misleading.
The agency told Boehringer Ingelheim to add the following clarification: “That means that, in a large clinical study, 3.4% of patients taking warfarin had a stroke, compared to 2.2% of patients taking Pradaxa.” So, in absolute terms, the difference between the drugs was 1.2%.
Potential need for monitoring
According to POGO, Boehringer Ingelheim has been the target of thousands of lawsuits regarding adverse events and deaths thought to be related to dabigatran. In 2013, Boehringer Ingelheim was fined by a federal judge for withholding or failing to preserve records.
Some of these documents suggested that patients taking dabigatran may require monitoring to ensure they remain within a therapeutic range. A scientist at Boehringer Ingelheim, Thorsten Lehr, drafted a paper concluding that there is a therapeutic range for dabigatran.
But company emails indicated that other employees were against publishing this paper. An email from Boehringer Ingelheim’s Jutta Heinrich-Nols said publishing the paper would “make any defense of no monitoring . . . extremely difficult . . . and undermine our efforts to compete” with other new anticoagulants.
For more details, see POGO’s full report. POGO is a nonpartisan, independent watchdog that champions government reform.
Anticoagulant granted fast track designation
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Image by Kevin MacKenzie
The US Food and Drug Administration (FDA) has granted fast track designation to betrixaban as extended-duration venous thromboembolism (VTE) prophylaxis for acute medically ill patients.
This includes patients who are hospitalized for serious medical conditions such as heart failure, stroke, infection, and pulmonary disease.
Betrixaban is an investigational oral anticoagulant that directly inhibits the activity of factor Xa.
According to Portola Pharmaceuticals, the company developing betrixaban, the drug has distinct properties that may allow it to demonstrate clinical benefit without significantly increasing the risk of fatal bleeding and certain other serious side effects.
These benefits include a 19- to 25-hour half-life for once-daily dosing, a low peak-to-trough drug concentration ratio that minimizes anticoagulant variability, low renal clearance, and no significant CYP3A4 metabolism, which may reduce the risk of drug-drug interactions.
Betrixaban trials
In the phase 2 Explore-Xa trial, researchers compared betrixaban and warfarin in patients with atrial fibrillation. The team randomized 508 patients to 1 of 3 blinded doses of betrixaban (40 mg, 60 mg, or 80 mg once daily) or unblinded warfarin, adjusted to an international normalized ratio of 2.0-3.0.
The primary outcome was major or clinically relevant non-major bleeding. At a mean follow-up of 147 days, the primary outcome had been met by 1 patient in the 40 mg betrixaban arm, 5 each in the 60 mg and 80 mg betrixaban arms, and 7 in the warfarin arm.
One patient each in the 60 mg and 80 mg arms experienced an ischemic stroke. And there were 2 vascular deaths, 1 each in the 40 mg arm and the warfarin arm.
In the phase 2 EXPERT trial, researchers compared betrixaban and enoxaparin as VTE prophylaxis in patients who underwent total knee replacement.
The team enrolled 215 patients and assigned them to 1 of 3 post-operative prophylaxis regimens: betrixaban at 15 mg twice daily, betrixaban at 40 mg twice daily, or enoxaparin at 30 mg every 12 hours—all for 10 to 14 days.
The primary efficacy outcome was the incidence of VTE during the dosing period, and 175 patients were evaluable for this outcome. VTE occurred in 20% of patients in the 15 mg betrixaban arm (14/70), 15% in the 40 mg betrixaban arm (10/65), and 10% (4/40) in the enoxaparin arm.
Safety outcomes included major and clinically significant non-major bleeds through 48 hours after treatment. There were no bleeds in the 15 mg betrixaban arm, 2 (2.4%) clinically significant non-major bleeds in the 40 mg betrixaban arm, and 1 (2.3%) major bleed and 2 (4.6%) clinically significant non-major bleeds in the enoxaparin arm.
Betrixaban is currently being tested in the phase 3 APEX trial for the prevention of VTE in acute medically ill patients. Portola said it expects to complete enrollment in APEX by the end of this year and report top-line data in the first quarter of 2016.
If the trial is successful, the company plans to submit a new drug application to the FDA later in 2016 under the fast track designation.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
CHMP grants accelerated assessment for MM drug
Photo by Linda Bartlett
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.
The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).
The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
About daratumumab
Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.
In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.
The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.
Daratumumab trials
The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.
The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.
The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.
Most adverse events in this study were grade 1 or 2, although serious events did occur.
The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.
Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.
Photo by Linda Bartlett
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.
The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).
The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
About daratumumab
Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.
In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.
The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.
Daratumumab trials
The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.
The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.
The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.
Most adverse events in this study were grade 1 or 2, although serious events did occur.
The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.
Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.
Photo by Linda Bartlett
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has agreed to provide accelerated assessment for daratumumab.
The drug is under review as monotherapy for patients with relapsed and refractory multiple myeloma (MM).
The CHMP grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.
Accelerated assessment shortens the review period from 210 days to 150 days.
About daratumumab
Daratumumab is an investigational monoclonal antibody that works by binding to CD38 on the surface of MM cells. In doing so, daratumumab triggers the patient’s own immune system to attack MM cells, resulting in cell death through multiple mechanisms of action.
In July 2013, daratumumab was granted orphan drug status by the European Medicines Agency for the treatment of plasma cell myeloma.
The drug has been accepted for priority review in the US as monotherapy for MM patients who are refractory to both a proteasome inhibitor and an immunomodulatory agent or who have received 3 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement that granted Janssen an exclusive worldwide license to develop, manufacture, and commercialize daratumumab.
Daratumumab trials
The marketing authorization application for daratumumab includes data from the phase 2 MMY2002 (SIRIUS) study, the phase 1/2 GEN501 study, and 3 additional supportive studies.
The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.
The results suggested that daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%.
Most adverse events in this study were grade 1 or 2, although serious events did occur.
The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 of the patients received the drug at 16 mg/kg.
Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.
CHMP recommends product for hemophilia A
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to
deliver its final decision within 3 months.
If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).
The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
Efmoroctocog alfa development
Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.
Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to
deliver its final decision within 3 months.
If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).
The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
Efmoroctocog alfa development
Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.
Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for the recombinant factor VIII Fc fusion protein efmoroctocog alfa (Elocta) to treat patients with hemophilia A.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to
deliver its final decision within 3 months.
If approved by the EC, efmoroctocog alfa would be the first hemophilia A treatment with prolonged circulation available in the European Union (plus Iceland, Lichtenstein, and Norway).
The CHMP’s positive opinion of efmoroctocog alfa was based on results from 2 phase 3 studies—A-LONG and Kids A-LONG.
A-LONG
The A-LONG study included 165 previously treated males 12 years of age and older with severe hemophilia A. Researchers evaluated individualized and weekly prophylaxis to reduce or prevent bleeding episodes and on-demand dosing to treat bleeding episodes.
Prophylaxis with efmoroctocog alfa resulted in low annualized bleeding rates, and a majority of bleeding episodes were controlled with a single injection of efmoroctocog alfa.
None of the patients developed neutralizing antibodies, efmoroctocog alfa was considered well-tolerated, and the product had a prolonged half-life when compared with rFVIII.
Kids A-LONG
The Kids A-LONG study included 71 boys (younger than 12) with severe hemophilia A who had at least 50 prior exposure days to FVIII therapies.
The children saw their median annualized bleeding rate decrease with efmoroctocog alfa, and close to half of the children did not have any bleeding episodes while they were receiving efmoroctocog alfa.
None of the patients developed inhibitors, and researchers said adverse events were typical of a pediatric hemophilia population.
ASPIRE
Participants in both the A-LONG and Kids A-LONG trials were able to enroll in ASPIRE, a phase 3 extension study evaluating the long-term safety and efficacy of efmoroctocog alfa.
Interim results of ASPIRE suggested that extended treatment with efmoroctocog alfa was largely safe and effective.
Efmoroctocog alfa development
Elocta is the European trade name for efmoroctocog alfa, which is known as Eloctate in the US, Canada, Australia, New Zealand, and Japan, where it is approved for the treatment of hemophilia A.
Biogen and Sobi are collaboration partners in the development and commercialization of efmoroctocog alfa for hemophilia A.
Last year, Sobi exercised its opt-in right to assume final development and commercialization of efmoroctocog alfa in the Sobi territories (essentially, Europe, North Africa, Russia, and certain countries in the Middle East). Biogen leads development for efmoroctocog alfa, has manufacturing rights, and has commercialization rights in North America and all other regions in the world excluding the Sobi territories.
CHMP endorses expanded indication for azacitidine
Image by Lance Liotta
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).
The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.
The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.
Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.
AML-001 trial
The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.
Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.
Patients were then randomized to receive either azacitidine (75 mg/m2/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).
Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).
One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.
Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.
Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively.
Image by Lance Liotta
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).
The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.
The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.
Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.
AML-001 trial
The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.
Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.
Patients were then randomized to receive either azacitidine (75 mg/m2/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).
Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).
One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.
Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.
Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively.
Image by Lance Liotta
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the marketing authorization for azacitidine for injection (Vidaza).
The CHMP is recommending that azacitidine be approved to treat adults age 65 and older with acute myeloid leukemia (AML) who are not eligible for hematopoietic stem cell transplant (HSCT) and have more than 30% blasts according to the WHO classification.
The CHMP’s recommendation will be reviewed by the European Commission (EC). The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision in 2 months.
The CHMP said this new indication for azacitidine would bring significant clinical benefit in comparison with existing therapies. If the EC follows the CHMP’s recommendation, azacitidine will receive extended market protection in all its indications for an additional year throughout the European Economic Area.
Azacitidine is already approved in the European Economic Area for the treatment of HSCT-ineligible adults diagnosed with intermediate-2- and high-risk myelodysplastic syndromes; chronic myelomonocytic leukemia with 10%-29% marrow blasts without myeloproliferative disorder; or AML with 20%-30% blasts and multi-lineage dysplasia.
AML-001 trial
The CHMP’s recommendation to expand the indication of azacitidine in AML was based on data from the AML-001 trial. This randomized study included patients age 65 and older with newly diagnosed or secondary AML with greater than 30% blasts.
Patients were pre-selected to receive 1 of 3 regimens per investigator’s choice. This included intensive chemotherapy (standard 7+3 regimen), low-dose cytarabine (20 mg subcutaneously twice a day for 10 days of each 28-day cycle) or best supportive care only.
Patients were then randomized to receive either azacitidine (75 mg/m2/day subcutaneously for 7 days of each 28-day cycle, n=241) or their predetermined conventional care regimen (CCR, n=247).
Median overall survival, the study’s primary endpoint, was 10.4 months for patients receiving azacitidine and 6.5 months for patients receiving CCR (hazard ratio=0.85, P=0.1009).
One-year survival rates with azacitidine and CCR were 46.5% and 34.2%, respectively.
Grade 3/4 anemia occurred in 16% of patients who received azacitidine, 5% who received best supportive care, 23% who received low-dose cytarabine, and 14% who received intensive chemotherapy.
Grade 3/4 neutropenia occurred in 26%, 5%, 25%, and 33%, respectively. Grade 3/4 febrile neutropenia occurred in 28%, 28%, 30%, and 31%, respectively. And grade 3/4 thrombocytopenia occurred in 24%, 5%, 28%, and 21%, respectively.
CHMP recommends blinatumomab for ALL
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.
The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.
The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for blinatumomab (Blincyto) to treat adults with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-precursor acute lymphoblastic leukemia (ALL).
Blinatumomab is a bispecific T-cell engager (BiTE®) antibody construct that binds to CD19 on the surface of B cells and CD3 on the surface of T cells.
The product already has conditional approval in the US to treat patients with relapsed or refractory Ph- B-precursor ALL.
The CHMP’s positive opinion of blinatumomab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder is required to complete ongoing studies or conduct new studies with the goal of confirming that a drug’s benefit-risk balance is positive.
Conditional marketing authorization is converted to a full authorization once these commitments have been fulfilled.
The conditional marketing authorization application for blinatumomab is based on a pair of phase 2 trials—Study ‘211 and Study ‘206.
Study ‘211
Results of Study ‘211 were presented at EHA 2014. The trial included 189 patients with Ph- relapsed or refractory B-precursor ALL.
The primary endpoint was complete remission or complete remission with partial hematologic recovery (CR/CRh). About 43% of patients achieved this endpoint within 2 cycles of therapy.
According to researchers, the most serious adverse events in this study were infection (31.7%), neurologic events (16.4%), neutropenia/febrile neutropenia (15.3%), cytokine release syndrome (CRS, 0.5%), and tumor lysis syndrome (0.5%).
Study ‘206
Results of Study ‘206 were presented at ASCO 2012. The trial included 36 patients with relapsed or refractory B-precursor ALL.
In this trial, the CR/CRh rate was 69.4% (25/36), with 15 patients achieving a CR (41.7%), and 10 patients achieving CRh (27.8%).
The “medically important” adverse events in this study, according to researchers, were CRS (n=3), central nervous system (CNS) events (3 seizures and 3 cases of encephalopathy), and fungal infection resulting in death (n=1).
However, the researchers found they could prevent CRS with dexamethasone. In addition, the CNS events were reversible, and blinatumomab could be reintroduced in 4 of the 6 patients with CNS events.
Blinatumomab is under development by Amgen. For more details on the drug, visit www.blincyto.com.
CHMP recommends authorization for idarucizumab
Image by Andre E.X. Brown
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.
Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).
Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.
The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.
Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.
Image by Andre E.X. Brown
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.
Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).
Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.
The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.
Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.
Image by Andre E.X. Brown
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) is recommending that idarucizumab receive marketing authorization in the European Union.
Idarucizumab (to be marketed as Praxbind) is a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa).
Idarucizumab is intended for patients who must undergo emergency surgery/urgent procedures and those who experience uncontrolled or life-threatening bleeding while on dabigatran.
The CHMP’s positive opinion of idarucizumab will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union, as well as Iceland, Lichtenstein, and Norway.
The CHMP’s positive opinion was based on results with idarucizumab in healthy volunteers and an interim analysis of the phase 3 RE-VERSE AD trial.
In the study of healthy volunteers, the pharmacokinetic profile of idarucizumab met the requirement for rapid peak exposure and rapid elimination, with no effect on pharmacodynamic parameters. And researchers said the drug was well tolerated.
In RE-VERSE AD, researchers evaluated idarucizumab in emergency settings. The drug normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.
The researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.
Idarucizumab is being developed by Boehringer Ingelheim, the company that makes dabigatran.
Idarucizumab is currently under review by regulatory authorities worldwide, including the US Food and Drug Administration. Boehringer Ingelheim plans to submit idarucizumab in all countries where dabigatran is licensed.
NICE backs discounted idelalisib for CLL
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).
NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.
This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.
Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.
NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.
NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.
Clinical effectiveness
The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.
For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.
Cost-effectiveness
Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.
Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.
Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.
The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).
Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).
NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.
This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.
Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.
NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.
NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.
Clinical effectiveness
The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.
For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.
Cost-effectiveness
Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.
Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.
Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.
The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).
Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).
The UK’s National Institute for Health and Care Excellence (NICE) has issued a final draft guidance recommending that the PI3Kδ inhibitor idelalisib (Zydelig) be made available on the National Health Service (NHS) for some adults with chronic lymphocytic leukemia (CLL).
NICE is recommending idelalisib in combination with rituximab for adults with previously untreated CLL who have a 17p deletion or TP53 mutation and for adults with CLL who have relapsed within 24 months of their previous treatment.
This decision follows a preliminary decision earlier this year, when NICE asked Gilead Sciences, the company developing idelalisib, to provide further information on the cost-effectiveness of the drug.
Gilead responded by submitting new economic analyses and a simple discount agreement to the list price of idelalisib.
NICE’s recommendation for idelalisib is contingent upon the company providing the agreed upon discount.
NICE’s draft guidance is now with consultees, who have the opportunity to appeal against it. Until NICE issues a final guidance, NHS bodies should make decisions locally on the funding of specific treatments.
Patients whose treatment with idelalisib is not recommended in this NICE guidance but was started within the NHS before this guidance was published should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.
Clinical effectiveness
The committee advising NICE concluded that idelalisib could not be recommended for patients whose disease had relapsed more than 24 months after previous treatment, as no evidence was submitted for this patient group.
For the other populations, the clinical effectiveness data from Study 116 showed that idelalisib plus rituximab produced a significant improvement in progression-free survival and overall survival, compared with rituximab alone, for patients with high-risk, relapsed or refractory CLL.
Cost-effectiveness
Idelalisib is priced at £3114.75 for sixty 150-mg tablets (British national formulary 2015). The mean cost of a 1-year treatment course is £37,922.
Gilead’s agreement provides a discount to the list price of idelalisib, but the level of the discount is currently confidential.
Analyses suggested that, at the discount agreement price, idelalisib plus rituximab was associated with higher costs and greater quality-adjusted life-year (QALY) gains when compared with rituximab alone.
The deterministic incremental cost-effectiveness ratio (ICER) for idelalisib plus rituximab compared with rituximab alone was £13,634 per QALY gained (incremental costs £26,128; incremental QALYs 1.92).
Compared with best supportive care, the ICER for idelalisib plus rituximab was £20,461 per QALY gained (incremental costs £39,211; incremental QALYs 1.92). And compared with ofatumumab, the ICER was £1527 per QALY gained (incremental costs £2926; incremental QALYs 1.92).
CHMP recommends carfilzomib for MM
Photo courtesy of Amgen
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).
The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The CHMP’s positive opinion will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.
ASPIRE trial
The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Carfilzomib development
Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.
Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.
Photo courtesy of Amgen
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).
The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The CHMP’s positive opinion will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.
ASPIRE trial
The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Carfilzomib development
Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.
Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.
Photo courtesy of Amgen
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion of the proteasome inhibitor carfilzomib (Kyprolis).
The CHMP is recommending the drug be approved for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.
The CHMP’s positive opinion will be reviewed by the European Commission (EC).
The EC usually follows the CHMP’s recommendations and is expected to deliver its final decision within 3 months. The EC’s decision will apply to the 28 member countries of the European Union (EU), as well as Iceland, Lichtenstein, and Norway.
ASPIRE trial
The CHMP’s positive opinion of carfilzomib was based on data from the phase 3 ASPIRE trial, which were presented at ASH 2014 and published in NEJM.
The trial enrolled 792 patients with relapsed or refractory MM who had received 1 to 3 prior lines of therapy. The patients were randomized (1:1) to receive carfilzomib plus lenalidomide and dexamethasone (KRd) or just lenalidomide and dexamethasone (Rd) for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned cross-over from the control arm to treatment with carfilzomib.
The study’s primary endpoint was progression-free survival. And the median progression-free survival was significantly longer in the KRd arm than the Rd arm—26.3 months and 17.6 months, respectively (hazard ratio=0.69, P=0.0001).
At the time of analysis, the difference in overall survival did not reach the prespecified boundary for statistical significance.
The overall response rate was 87% in the KRd arm and 67% in the Rd arm. The median duration of response was 28.6 months and 21.2 months, respectively.
The rates of death due to adverse events (AEs) within 30 days of the last dose were similar between the treatment arms.
The most common causes of death not due to progressive disease occurring in patients in the KRd arm and the Rd arm, respectively, were cardiac disorders (3% vs 2%), infection (2% vs 3%), renal events (0% vs less than 1%), and other AEs (2% vs 3%).
Serious AEs were reported in 60% of the patients in the KRd arm and 54% in the Rd arm. The most common serious AEs reported in the KRd arm and the Rd arm, respectively, were pneumonia (14% vs 11%), respiratory tract infection (4% vs 2%), pyrexia (4% vs 2%), and pulmonary embolism (3% vs 2%).
Carfilzomib development
Carfilzomib was granted orphan drug designation in the EU in 2008. Last February, the drug’s application for EU approval was granted accelerated assessment.
Carfilzomib was approved as monotherapy in the US in July 2012 and in combination with lenalidomide and dexamethasone in July 2015. Carfilzomib is also approved for use in Argentina, Israel, Kuwait, Mexico, and Thailand.
Carfilzomib is a product of Onyx Pharmaceuticals, Inc., a subsidiary of Amgen that holds development and commercialization rights to the drug globally, excluding Japan. For more information on the drug, visit www.kyprolis.com.