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Nilotinib approved to treat kids with CML in EU
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation. 
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation.
The European Commission has approved nilotinib (Tasigna®) for the treatment of pediatric patients.
The drug is now approved to treat children age 2 and older with newly diagnosed, Philadelphia chromosome-positive (Ph+), chronic phase (CP) chronic myeloid leukemia (CML) or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
Nilotinib is the only second-generation tyrosine kinase inhibitor currently approved in the European Union (EU) for the treatment of Ph+ CP-CML in children. The approval applies to all EU member states.
According to Novartis, the expanded indication for nilotinib is based on 2 prospective studies of the drug in children with Ph+ CP-CML, which were part of a formal “pediatric investigation plan” agreed upon with the European Medicines Agency.
The company said 69 patients received nilotinib in these studies. The patients ranged in age from 2 to 18. They had either newly diagnosed Ph+ CP-CML or Ph+ CP-CML with resistance or intolerance to prior therapy, including imatinib.
In the newly diagnosed patients, the major molecular response (MMR) rate was 60.0% (95% CI: 38.7, 78.9) at 12 cycles, with 15 patients achieving MMR.
In patients with resistance or intolerance to prior therapy, the MMR rate was 40.9% (95% CI: 26.3, 56.8) at 12 cycles, with 18 patients being in MMR.
In newly diagnosed patients, the cumulative MMR rate was 64.0% by cycle 12. In patients with resistance or intolerance to prior therapy, the cumulative MMR rate was 47.7% by cycle 12.
Adverse events were generally consistent with those observed in adults, with the exception of hyperbilirubinemia and transaminase elevation, which were reported at a higher frequency than in adults.
The rate of grade 3/4 hyperbilirubinemia was 13.0%, the rate of grade 3/4 AST elevation was 1.4%, and the rate of grade 3/4 ALT elevation was 8.7%.
There were no deaths on treatment or after treatment discontinuation.
Product approved to treat patients with hemophilia A and inhibitors
The US Food and Drug Administration (FDA) has approved use of emicizumab-kxwh (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.
Emicizumab is approved as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A and factor VIII (FVIII) inhibitors.
Emicizumab can be self-administered once-weekly via subcutaneous injection.
The labeling for emicizumab contains a boxed warning noting that patients who received emicizumab in conjunction with activated prothrombin complex concentrate developed thrombotic microangiopathy (TMA) and thromboembolic events (TEs).
Therefore, patients should discontinue prophylactic use of bypassing agents (BPAs) the day before starting prophylaxis with emicizumab.
The FDA granted the approval of emicizumab to Genentech, Inc. The agency granted the application for emicizumab priority review, and the product received breakthrough therapy and orphan drug designations.
Access to emicizumab
According to Genentech, emicizumab will be available shortly.
The company said it will be offering comprehensive services to help minimize barriers to access and reimbursement. Patients can call 866-436-5427 (866-HEMLIBRA) for more information.
For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is available at 866-422-2377 (866-4ACCESS) or http://www.Genentech-Access.com.
Emicizumab trials
The biologics license application for emicizumab was supported by results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with BPAs on-demand or as prophylaxis.
The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.
There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced TEs, and 3 had TMA while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
In this single-arm trial, researchers evaluated emicizumab prophylaxis in children younger than 12 years of age who had hemophilia A with FVIII inhibitors.
The interim efficacy analysis, after at least 12 weeks of treatment, included 23 children.
After a median observation time of 38.1 weeks, 87% (95% CI: 66.4; 97.2) of children who received emicizumab experienced 0 treated bleeds. The percentage with 0 treated or non-treated bleeds was lower, at 34.8% (95% CI: 16.4; 57.3).
The most common adverse events (observed in at least 10% of patients) were mild injection site reactions and nasopharyngitis. No TEs or TMAs were observed.
HAVEN 3 and 4
Emicizumab is now being studied in 2 additional phase 3 trials.
In HAVEN 3, researchers are evaluating emicizumab prophylaxis dosed once weekly or once every other week in patients age 12 and older with hemophilia A without FVIII inhibitors.
In HAVEN 4, researchers are evaluating emicizumab prophylaxis dosed every 4 weeks in patients age 12 and older with hemophilia A, with or without inhibitors.
The US Food and Drug Administration (FDA) has approved use of emicizumab-kxwh (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.
Emicizumab is approved as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A and factor VIII (FVIII) inhibitors.
Emicizumab can be self-administered once-weekly via subcutaneous injection.
The labeling for emicizumab contains a boxed warning noting that patients who received emicizumab in conjunction with activated prothrombin complex concentrate developed thrombotic microangiopathy (TMA) and thromboembolic events (TEs).
Therefore, patients should discontinue prophylactic use of bypassing agents (BPAs) the day before starting prophylaxis with emicizumab.
The FDA granted the approval of emicizumab to Genentech, Inc. The agency granted the application for emicizumab priority review, and the product received breakthrough therapy and orphan drug designations.
Access to emicizumab
According to Genentech, emicizumab will be available shortly.
The company said it will be offering comprehensive services to help minimize barriers to access and reimbursement. Patients can call 866-436-5427 (866-HEMLIBRA) for more information.
For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is available at 866-422-2377 (866-4ACCESS) or http://www.Genentech-Access.com.
Emicizumab trials
The biologics license application for emicizumab was supported by results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with BPAs on-demand or as prophylaxis.
The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.
There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced TEs, and 3 had TMA while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
In this single-arm trial, researchers evaluated emicizumab prophylaxis in children younger than 12 years of age who had hemophilia A with FVIII inhibitors.
The interim efficacy analysis, after at least 12 weeks of treatment, included 23 children.
After a median observation time of 38.1 weeks, 87% (95% CI: 66.4; 97.2) of children who received emicizumab experienced 0 treated bleeds. The percentage with 0 treated or non-treated bleeds was lower, at 34.8% (95% CI: 16.4; 57.3).
The most common adverse events (observed in at least 10% of patients) were mild injection site reactions and nasopharyngitis. No TEs or TMAs were observed.
HAVEN 3 and 4
Emicizumab is now being studied in 2 additional phase 3 trials.
In HAVEN 3, researchers are evaluating emicizumab prophylaxis dosed once weekly or once every other week in patients age 12 and older with hemophilia A without FVIII inhibitors.
In HAVEN 4, researchers are evaluating emicizumab prophylaxis dosed every 4 weeks in patients age 12 and older with hemophilia A, with or without inhibitors.
The US Food and Drug Administration (FDA) has approved use of emicizumab-kxwh (Hemlibra®), a bispecific factor IXa- and factor X-directed antibody.
Emicizumab is approved as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children who have hemophilia A and factor VIII (FVIII) inhibitors.
Emicizumab can be self-administered once-weekly via subcutaneous injection.
The labeling for emicizumab contains a boxed warning noting that patients who received emicizumab in conjunction with activated prothrombin complex concentrate developed thrombotic microangiopathy (TMA) and thromboembolic events (TEs).
Therefore, patients should discontinue prophylactic use of bypassing agents (BPAs) the day before starting prophylaxis with emicizumab.
The FDA granted the approval of emicizumab to Genentech, Inc. The agency granted the application for emicizumab priority review, and the product received breakthrough therapy and orphan drug designations.
Access to emicizumab
According to Genentech, emicizumab will be available shortly.
The company said it will be offering comprehensive services to help minimize barriers to access and reimbursement. Patients can call 866-436-5427 (866-HEMLIBRA) for more information.
For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is available at 866-422-2377 (866-4ACCESS) or http://www.Genentech-Access.com.
Emicizumab trials
The biologics license application for emicizumab was supported by results from a pair of phase 3 studies—HAVEN 1 and HAVEN 2.
Results from HAVEN 1 were published in NEJM and presented at the 26th ISTH Congress in July. Interim results from HAVEN 2 were presented at ISTH as well.
HAVEN 1
The study enrolled 109 patients (age 12 and older) with hemophilia A and FVIII inhibitors who were previously treated with BPAs on-demand or as prophylaxis.
The patients were randomized to receive emicizumab prophylaxis or no prophylaxis. On-demand treatment of breakthrough bleeds with BPAs was allowed.
There was a significant reduction in treated bleeds of 87% with emicizumab prophylaxis compared to no prophylaxis (95% CI: 72.3; 94.3, P<0.0001). And there was an 80% reduction in all bleeds with emicizumab (95% CI: 62.5; 89.8, P<0.0001).
Adverse events occurring in at least 5% of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection, and arthralgia.
Two patients experienced TEs, and 3 had TMA while receiving emicizumab prophylaxis and more than 100 u/kg/day of activated prothrombin complex concentrate, on average, for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa.
Neither TE required anticoagulation therapy, and 1 patient restarted emicizumab. The cases of TMA observed were transient, and 1 patient restarted emicizumab.
HAVEN 2
In this single-arm trial, researchers evaluated emicizumab prophylaxis in children younger than 12 years of age who had hemophilia A with FVIII inhibitors.
The interim efficacy analysis, after at least 12 weeks of treatment, included 23 children.
After a median observation time of 38.1 weeks, 87% (95% CI: 66.4; 97.2) of children who received emicizumab experienced 0 treated bleeds. The percentage with 0 treated or non-treated bleeds was lower, at 34.8% (95% CI: 16.4; 57.3).
The most common adverse events (observed in at least 10% of patients) were mild injection site reactions and nasopharyngitis. No TEs or TMAs were observed.
HAVEN 3 and 4
Emicizumab is now being studied in 2 additional phase 3 trials.
In HAVEN 3, researchers are evaluating emicizumab prophylaxis dosed once weekly or once every other week in patients age 12 and older with hemophilia A without FVIII inhibitors.
In HAVEN 4, researchers are evaluating emicizumab prophylaxis dosed every 4 weeks in patients age 12 and older with hemophilia A, with or without inhibitors.
FDA approves generic clofarabine
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
The US Food and Drug Administration (FDA) has approved Dr. Reddy’s Laboratories Ltd.’s Clofarabine Injection, a therapeutic equivalent generic version of Clolar® (clofarabine) Injection.
The generic drug is now approved to treat patients age 1 to 21 who have relapsed or refractory acute lymphoblastic leukemia and have received at least 2 prior treatment regimens.
Dr. Reddy’s Clofarabine Injection is available in single-dose, 20 mL flint vials containing 20 mg of clofarabine in 20 mL of solution (1 mg/mL).
Generic azacitidine approved in Canada
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
Health Canada has approved Dr. Reddy’s Laboratories Ltd.’s Azacitidine for Injection 100 mg/vial, a bioequivalent generic version of VIDAZA® (azacitidine for injection).
The generic drug is approved for the same indications as VIDAZA®.
This includes treating adults with intermediate-2 or high-risk myelodysplastic syndromes (according to the International Prognostic Scoring System) who are not eligible for hematopoietic stem cell transplant.
It also includes treating adults who have acute myeloid leukemia with 20% to 30% blasts and multi-lineage dysplasia (according to World Health Organization classification) who are not eligible for hematopoietic stem cell transplant.
“The approval and launch of Azacitidine for Injection is an important milestone for Dr. Reddy’s in Canada,” said Vinod Ramachandran, PhD, country manager, Dr. Reddy’s Canada.
“The launch of the first generic azacitidine for injection is another step in our long-term commitment to bring more cost-effective options to Canadian patients.”
CHMP backs therapy for hemophilia A
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).
Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).
The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).
Phase 3 trials
Rurioctocog alfa pegol has been studied in 3 phase 3 trials.
One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.
Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.
A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).
Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).
The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).
Phase 3 trials
Rurioctocog alfa pegol has been studied in 3 phase 3 trials.
One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.
Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.
A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for rurioctocog alfa pegol (Adynovi).
Rurioctocog alfa pegol (formerly BAX 855) is a pegylated, full-length, recombinant factor VIII product built on a licensed recombinant factor VIII product (Advate).
The CHMP is recommending that rurioctocog alfa pegol be approved for the treatment and prophylaxis of bleeding in patients age 12 and older with hemophilia A.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
If approved, rurioctocog alfa pegol would be available as a powder and solvent for solution for injection (250 IU, 500 IU, 1000 IU, and 2000 IU).
Phase 3 trials
Rurioctocog alfa pegol has been studied in 3 phase 3 trials.
One study (phase 2/3) included 137 patients, age 12 and older, with previously treated hemophilia A. Results from this trial were published in Blood in July 2015.
Another study included 15 patients with severe hemophilia A who were undergoing surgical procedures. Results were published in Haemophilia in June 2016.
A third study included 66 patients, age 12 and younger, who had previously treated hemophilia A. Results from this trial were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.
CHMP wants to expand use of BV to include CTCL
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).
The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The EC previously approved BV to treat:
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
- Adults with CD30+ HL at increased risk of relapse or progression following ASCT
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).
The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The EC previously approved BV to treat:
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
- Adults with CD30+ HL at increased risk of relapse or progression following ASCT
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for brentuximab vedotin (BV, Adcetris).
The CHMP is recommending authorization of BV to treat adults with CD30+ cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The EC previously approved BV to treat:
- Adults with relapsed or refractory CD30+ Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT) or following at least 2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option
- Adults with CD30+ HL at increased risk of relapse or progression following ASCT
- Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.
The CHMP’s recommendation to approve BV for CTCL is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in July 2015 and August 2015.
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
CHMP recommends letermovir as CMV prophylaxis
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.
Phase 3 trial
The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.
The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.
Phase 3 trial
The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.
The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorization for letermovir (Prevymis), which belongs to a class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The CHMP is advocating that letermovir be approved as prophylaxis for cytomegalovirus (CMV) reactivation and disease in patients who receive immunosuppressants after allogeneic hematopoietic stem cell transplant (HSCT).
The CHMP’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Letermovir previously received an orphan designation from the European Medicines Agency’s Committee for Orphan Medicinal Products in June 2012. Now, the committee will assess whether the orphan designation should be maintained.
Phase 3 trial
The CHMP’s recommendation to authorize use of letermovir is based on data from a phase 3 trial. Results from this trial were presented at the 2017 BMT Tandem Meetings.
The trial enrolled adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
CHMP recommends approval of romiplostim in kids
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate®) to include children.
The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.
The committee’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.
Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.
And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate®) to include children.
The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.
The committee’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.
Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.
And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the approved indication for romiplostim (Nplate®) to include children.
The CHMP is recommending authorization of romiplostim to treat patients age 1 and older who have chronic immune thrombocytopenia (ITP) that is refractory to other treatments.
The committee’s opinion will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, a centralized marketing authorization will be granted that will be valid in the European Union. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
The recommendation for romiplostim was based on 5 studies of the drug in children with ITP. This includes 4 completed studies—a phase 1/2, a phase 3, and 2 long-term safety and efficacy studies—and 1 ongoing long-term study.
Results from the phase 1/2 trial were published in Blood in 2011. Phase 3 results were published in The Lancet in April of last year.
And results from 2 of the long-term trials were presented at 22nd Congress of the European Hematology Association in June (abstract P367 and abstract P727).
Dasatinib approved to treat kids with CML
The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel®).
The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
This approval was granted under priority review, and the drug received orphan designation for this indication.
The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.
The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.
For more details, see the full prescribing information.
Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
Pediatric studies
The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.
There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.
Ninety-one patients received dasatinib at 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.
The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.
The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).
At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.
At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.
The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.
Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).
The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel®).
The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
This approval was granted under priority review, and the drug received orphan designation for this indication.
The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.
The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.
For more details, see the full prescribing information.
Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
Pediatric studies
The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.
There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.
Ninety-one patients received dasatinib at 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.
The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.
The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).
At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.
At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.
The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.
Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).
The US Food and Drug Administration (FDA) has expanded the approved use of dasatinib (Sprycel®).
The drug is now approved to treat children with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
This approval was granted under priority review, and the drug received orphan designation for this indication.
The recommended starting dosage for dasatinib in pediatric patients with chronic phase, Ph+ CML is based on body weight.
The recommended dose should be administered orally once daily, and the dose should be recalculated every 3 months based on changes in body weight or more often if necessary.
For more details, see the full prescribing information.
Dasatinib is also approved by the FDA to treat adults with newly diagnosed chronic phase, Ph+ CML; chronic, accelerated, or myeloid/lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and Ph+ acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
Pediatric studies
The approval of dasatinib in pediatric CML patients was supported by 2 studies. Results from the phase 1 study (NCT00306202) were published in the Journal of Clinical Oncology in 2013. Phase 2 (NCT00777036) results were presented at the 2017 ASCO Annual Meeting.
There were 97 patients in the 2 studies who had chronic phase CML and received oral dasatinib—17 from phase 1 and 80 from phase 2. Fifty-one of the patients had newly diagnosed CML, and 46 patients were resistant or intolerant to previous treatment with imatinib.
Ninety-one patients received dasatinib at 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high body surface area). Patients were treated until disease progression or unacceptable toxicity.
The median duration of treatment was 51.1 months, or 4.3 years (range, 1.9 to 99.6 months). The median follow-up was 4.5 years in the newly diagnosed patients and 5.2 years in patients who had previously received imatinib.
The efficacy endpoints were complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR).
At 12 months, the CCyR rate was 96.1% in newly diagnosed patients and 78.3% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 56.9% and 39.1%, respectively.
At 24 months, the CCyR rate was 96.1% in newly diagnosed patients and 82.6% in patients who had prior treatment with imatinib. The MCyR rate was 98.0% and 89.1%, respectively. And the MMR rate was 74.5% and 52.2%, respectively.
The median durations of CCyR, MCyR and MMR could not be estimated, as more than half of the responding patients had not progressed at the time of data cut-off.
Drug-related serious adverse events were reported in 14.4% of dasatinib-treated patients. The most common adverse events (≥15%) were headache (28%), nausea (20%), diarrhea (21%), skin rash (19%), pain in extremity (19%), and abdominal pain (16%).
FDA approves letermovir as CMV prophylaxis
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings.
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings.
The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).
Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.
The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.
“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.
Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)
The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.
Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.
For more details on letermovir, see the full prescribing information.
Trial results
The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.
Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.
Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).
Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.
Reasons for failure (in the letermovir and placebo arms, respectively) included:
- Clinically significant CMV infection—18% vs 42%
- Initiation of PET based on documented CMV viremia—16% vs 40%
- CMV end-organ disease—2% for both
- Study discontinuation before week 24—17% vs 16%
- Missing outcome in week 24 visit window—3% for both.
The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).
The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.
Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).
The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).
Results from this trial were presented at the 2017 BMT Tandem Meetings.