Pharmacy

Image from Graham Beards

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for avatrombopag.

Avatrombopag is a second-generation thrombopoietin receptor agonist that is intended to address the limitations of existing treatments for thrombocytopenia.

With this NDA, Dova Pharmaceuticals, Inc., is seeking approval of avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure.

The FDA expects to make a decision on the NDA by May 21, 2018.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Phase 3 trials

The NDA submission for avatrombopag is supported by 2 identically designed phase 3 trials, ADAPT 1 and ADAPT 2. Results from these trials were presented at the 2017 American Association for the Study of Liver Disease (AASLD) Meeting last month (abstract 217).

The studies randomized 435 patients with thrombocytopenia and chronic liver disease who were scheduled to undergo a procedure.

Patients with low baseline platelet counts (<40x 10⁹/L) were randomized to receive 60 mg of avatrombopag or placebo daily for 5 days.

Patients with higher baseline platelet counts (40 to <50 x 10⁹/L) were randomized to receive 40 mg of avatrombopag or placebo daily for 5 days.

Patients underwent their procedures 5 to 8 days after their last dose of avatrombopag.

In ADAPT-1, 85 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 78 controls completed the study.

In ADAPT-2, 68 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 68 controls completed the study.

Efficacy

The primary efficacy endpoint of these trials was the proportion of patients who did not require any bleeding rescue up to 7 days post-procedure. Bleeding rescue included platelet transfusion, fresh frozen plasma, cryoprecipitate, vitamin K (phytonadione), desmopressin, recombinant activated factor VII, aminocaproicacid, tranexamic acid, whole blood transfusion, packed red cell transfusion, surgical intervention, or interventional radiology.

In ADAPT-1, the primary endpoint was achieved by 66% of patients who received avatrombopag at 60 mg and 23% of those who received placebo in the low-platelet-count cohort (P<0.0001). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 38% of controls in the higher-platelet-count cohort (P<0.0001).

In ADAPT-2, the primary endpoint was achieved by 69% of patients who received avatrombopag at 60 mg and 35% of those who received placebo in the low-platelet-count cohort (P<0.0006). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 33% of controls in the higher- platelet-count cohort (P<0.0001).

A secondary efficacy endpoint was the proportion of patients achieving the target platelet count (≥50 x 10⁹/L).

In ADAPT-1, this endpoint was met by 69% of patients who received avatrombopag at 60 mg and 4% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 88% of patients who received avatrombopag at 40 mg and 21% of controls in the higher-platelet-count cohort (P<0.0001)

In ADAPT-2, this endpoint was met by 67% of patients who received avatrombopag at 60 mg and 7% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 93% of patients who received avatrombopag at 40 mg and 39% of controls in the higher-platelet-count cohort (P<0.0001).

Safety

The researchers pooled safety data from the 2 trials.

Treatment-emergent adverse events (AEs) occurred in 58.2% of controls and 56% of avatrombopag-treated patients in the low-platelet-count cohort (60 mg). Treatment-emergent AEs also occurred in 50.8% of controls and 51.3% of avatrombopag-treated patients in the higher-platelet-count cohort (40 mg).

The most frequently reported treatment-emergent AEs were pyrexia, abdominal pain, nausea, headache, diarrhea, and fatigue.

One patient experienced partial portal vein thrombosis that was considered non-serious and potentially related to avatrombopag.

Treatment-related AEs occurred in 17.6% of controls and 11.3% of avatrombopag-treated patients in the low-platelet-count cohort. Treatment-related AEs also occurred in 6.2% of controls and 7% of avatrombopag-treated patients in the higher-platelet-count cohort.

Serious AEs occurred in 13.2%, 6.9%, 3.1%, and 7.8%, respectively.

There were 3 deaths—2 in the 40 mg avatrombopag arm in ADAPT-1 and 1 in the control group in ADAPT-2. None of the deaths was considered treatment-related.

Future directions

Dova Pharmaceuticals, Inc., is planning to explore the potential use of avatrombopag in a broader population of patients with thrombocytopenia. This includes patients undergoing surgical procedures associated with a high risk of bleeding and patients who develop thrombocytopenia after receiving chemotherapy.

In addition, the company is exploring a potential regulatory approval pathway for avatrombopag for the treatment of adults with chronic immune thrombocytopenic purpura based on results from a completed phase 3 trial in this patient population.

Image from Graham Beards

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for avatrombopag.

Avatrombopag is a second-generation thrombopoietin receptor agonist that is intended to address the limitations of existing treatments for thrombocytopenia.

With this NDA, Dova Pharmaceuticals, Inc., is seeking approval of avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure.

The FDA expects to make a decision on the NDA by May 21, 2018.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Phase 3 trials

The NDA submission for avatrombopag is supported by 2 identically designed phase 3 trials, ADAPT 1 and ADAPT 2. Results from these trials were presented at the 2017 American Association for the Study of Liver Disease (AASLD) Meeting last month (abstract 217).

The studies randomized 435 patients with thrombocytopenia and chronic liver disease who were scheduled to undergo a procedure.

Patients with low baseline platelet counts (<40x 10⁹/L) were randomized to receive 60 mg of avatrombopag or placebo daily for 5 days.

Patients with higher baseline platelet counts (40 to <50 x 10⁹/L) were randomized to receive 40 mg of avatrombopag or placebo daily for 5 days.

Patients underwent their procedures 5 to 8 days after their last dose of avatrombopag.

In ADAPT-1, 85 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 78 controls completed the study.

In ADAPT-2, 68 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 68 controls completed the study.

Efficacy

The primary efficacy endpoint of these trials was the proportion of patients who did not require any bleeding rescue up to 7 days post-procedure. Bleeding rescue included platelet transfusion, fresh frozen plasma, cryoprecipitate, vitamin K (phytonadione), desmopressin, recombinant activated factor VII, aminocaproicacid, tranexamic acid, whole blood transfusion, packed red cell transfusion, surgical intervention, or interventional radiology.

In ADAPT-1, the primary endpoint was achieved by 66% of patients who received avatrombopag at 60 mg and 23% of those who received placebo in the low-platelet-count cohort (P<0.0001). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 38% of controls in the higher-platelet-count cohort (P<0.0001).

In ADAPT-2, the primary endpoint was achieved by 69% of patients who received avatrombopag at 60 mg and 35% of those who received placebo in the low-platelet-count cohort (P<0.0006). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 33% of controls in the higher- platelet-count cohort (P<0.0001).

A secondary efficacy endpoint was the proportion of patients achieving the target platelet count (≥50 x 10⁹/L).

In ADAPT-1, this endpoint was met by 69% of patients who received avatrombopag at 60 mg and 4% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 88% of patients who received avatrombopag at 40 mg and 21% of controls in the higher-platelet-count cohort (P<0.0001)

In ADAPT-2, this endpoint was met by 67% of patients who received avatrombopag at 60 mg and 7% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 93% of patients who received avatrombopag at 40 mg and 39% of controls in the higher-platelet-count cohort (P<0.0001).

Safety

The researchers pooled safety data from the 2 trials.

Treatment-emergent adverse events (AEs) occurred in 58.2% of controls and 56% of avatrombopag-treated patients in the low-platelet-count cohort (60 mg). Treatment-emergent AEs also occurred in 50.8% of controls and 51.3% of avatrombopag-treated patients in the higher-platelet-count cohort (40 mg).

The most frequently reported treatment-emergent AEs were pyrexia, abdominal pain, nausea, headache, diarrhea, and fatigue.

One patient experienced partial portal vein thrombosis that was considered non-serious and potentially related to avatrombopag.

Treatment-related AEs occurred in 17.6% of controls and 11.3% of avatrombopag-treated patients in the low-platelet-count cohort. Treatment-related AEs also occurred in 6.2% of controls and 7% of avatrombopag-treated patients in the higher-platelet-count cohort.

Serious AEs occurred in 13.2%, 6.9%, 3.1%, and 7.8%, respectively.

There were 3 deaths—2 in the 40 mg avatrombopag arm in ADAPT-1 and 1 in the control group in ADAPT-2. None of the deaths was considered treatment-related.

Future directions

Dova Pharmaceuticals, Inc., is planning to explore the potential use of avatrombopag in a broader population of patients with thrombocytopenia. This includes patients undergoing surgical procedures associated with a high risk of bleeding and patients who develop thrombocytopenia after receiving chemotherapy.

In addition, the company is exploring a potential regulatory approval pathway for avatrombopag for the treatment of adults with chronic immune thrombocytopenic purpura based on results from a completed phase 3 trial in this patient population.

Image from Graham Beards

The US Food and Drug Administration (FDA) has granted priority review to the new drug application (NDA) for avatrombopag.

Avatrombopag is a second-generation thrombopoietin receptor agonist that is intended to address the limitations of existing treatments for thrombocytopenia.

With this NDA, Dova Pharmaceuticals, Inc., is seeking approval of avatrombopag for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo a procedure.

The FDA expects to make a decision on the NDA by May 21, 2018.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

Phase 3 trials

The NDA submission for avatrombopag is supported by 2 identically designed phase 3 trials, ADAPT 1 and ADAPT 2. Results from these trials were presented at the 2017 American Association for the Study of Liver Disease (AASLD) Meeting last month (abstract 217).

The studies randomized 435 patients with thrombocytopenia and chronic liver disease who were scheduled to undergo a procedure.

Patients with low baseline platelet counts (<40x 10⁹/L) were randomized to receive 60 mg of avatrombopag or placebo daily for 5 days.

Patients with higher baseline platelet counts (40 to <50 x 10⁹/L) were randomized to receive 40 mg of avatrombopag or placebo daily for 5 days.

Patients underwent their procedures 5 to 8 days after their last dose of avatrombopag.

In ADAPT-1, 85 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 78 controls completed the study.

In ADAPT-2, 68 patients completed treatment with avatrombopag at 60 mg, 55 completed treatment with avatrombopag at 40 mg, and 68 controls completed the study.

Efficacy

The primary efficacy endpoint of these trials was the proportion of patients who did not require any bleeding rescue up to 7 days post-procedure. Bleeding rescue included platelet transfusion, fresh frozen plasma, cryoprecipitate, vitamin K (phytonadione), desmopressin, recombinant activated factor VII, aminocaproicacid, tranexamic acid, whole blood transfusion, packed red cell transfusion, surgical intervention, or interventional radiology.

In ADAPT-1, the primary endpoint was achieved by 66% of patients who received avatrombopag at 60 mg and 23% of those who received placebo in the low-platelet-count cohort (P<0.0001). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 38% of controls in the higher-platelet-count cohort (P<0.0001).

In ADAPT-2, the primary endpoint was achieved by 69% of patients who received avatrombopag at 60 mg and 35% of those who received placebo in the low-platelet-count cohort (P<0.0006). The endpoint was also achieved by 88% of patients who received avatrombopag at 40 mg and 33% of controls in the higher- platelet-count cohort (P<0.0001).

A secondary efficacy endpoint was the proportion of patients achieving the target platelet count (≥50 x 10⁹/L).

In ADAPT-1, this endpoint was met by 69% of patients who received avatrombopag at 60 mg and 4% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 88% of patients who received avatrombopag at 40 mg and 21% of controls in the higher-platelet-count cohort (P<0.0001)

In ADAPT-2, this endpoint was met by 67% of patients who received avatrombopag at 60 mg and 7% of controls in the low-platelet-count cohort (P<0.0001). It was also met by 93% of patients who received avatrombopag at 40 mg and 39% of controls in the higher-platelet-count cohort (P<0.0001).

Safety

The researchers pooled safety data from the 2 trials.

Treatment-emergent adverse events (AEs) occurred in 58.2% of controls and 56% of avatrombopag-treated patients in the low-platelet-count cohort (60 mg). Treatment-emergent AEs also occurred in 50.8% of controls and 51.3% of avatrombopag-treated patients in the higher-platelet-count cohort (40 mg).

The most frequently reported treatment-emergent AEs were pyrexia, abdominal pain, nausea, headache, diarrhea, and fatigue.

One patient experienced partial portal vein thrombosis that was considered non-serious and potentially related to avatrombopag.

Treatment-related AEs occurred in 17.6% of controls and 11.3% of avatrombopag-treated patients in the low-platelet-count cohort. Treatment-related AEs also occurred in 6.2% of controls and 7% of avatrombopag-treated patients in the higher-platelet-count cohort.

Serious AEs occurred in 13.2%, 6.9%, 3.1%, and 7.8%, respectively.

There were 3 deaths—2 in the 40 mg avatrombopag arm in ADAPT-1 and 1 in the control group in ADAPT-2. None of the deaths was considered treatment-related.

Future directions

Dova Pharmaceuticals, Inc., is planning to explore the potential use of avatrombopag in a broader population of patients with thrombocytopenia. This includes patients undergoing surgical procedures associated with a high risk of bleeding and patients who develop thrombocytopenia after receiving chemotherapy.

In addition, the company is exploring a potential regulatory approval pathway for avatrombopag for the treatment of adults with chronic immune thrombocytopenic purpura based on results from a completed phase 3 trial in this patient population.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has granted orphan drug designation to rofecoxib (TRM-201) as a potential treatment for degenerative joint disease in hemophilia, also known as hemophilic arthropathy (HA).

Rofecoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) that was previously sold in the US under the name Vioxx.

Vioxx was FDA-approved to relieve the signs and symptoms of osteoarthritis, manage acute pain in adults, and treat primary dysmenorrhea.

Merck & Co. pulled Vioxx from the US market in 2004 due to safety concerns. The drug was shown to increase a person’s risk of cardiovascular events, including heart attack and stroke.

Now, Tremeau Pharmaceuticals, Inc., is working to bring rofecoxib back to market to treat patients with HA.

HA patients should not receive traditional NSAIDs due to their effects on platelet aggregation and the risk of gastrointestinal ulcers associated with these drugs. Therefore, high potency opioids are the current standard of care in HA.

“Being granted an orphan drug designation for rofecoxib by FDA is an important regulatory milestone for Tremeau and affirms our strategy of providing non-opioid pain treatments for rare diseases like hemophilic arthropathy,” said Bradford C. Sippy, chief executive officer of Tremeau.

Sippy is a former Merck employee who helped with the recall of Vioxx and knew the final patent protecting the drug’s monopoly was expiring this fall.

When it stopped making Vioxx, Merck was facing thousands of lawsuits from people claiming the drug caused their heart attacks or strokes.

Merck’s own research showed the drug doubled those risks, but lawyers for patients claimed the company downplayed or concealed that. Merck initially fought the lawsuits but, in 2007, agreed to a $4.85 billion settlement.

If approved to treat HA, rofecoxib would carry a warning about the increased risk of heart attack and stroke associated with the drug.

Although the orphan designation for rofecoxib is a step toward FDA approval, Sippy said Tremeau must still raise $25 million or more to fund trials of the drug in hemophilia patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has granted orphan drug designation to rofecoxib (TRM-201) as a potential treatment for degenerative joint disease in hemophilia, also known as hemophilic arthropathy (HA).

Rofecoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) that was previously sold in the US under the name Vioxx.

Vioxx was FDA-approved to relieve the signs and symptoms of osteoarthritis, manage acute pain in adults, and treat primary dysmenorrhea.

Merck & Co. pulled Vioxx from the US market in 2004 due to safety concerns. The drug was shown to increase a person’s risk of cardiovascular events, including heart attack and stroke.

Now, Tremeau Pharmaceuticals, Inc., is working to bring rofecoxib back to market to treat patients with HA.

HA patients should not receive traditional NSAIDs due to their effects on platelet aggregation and the risk of gastrointestinal ulcers associated with these drugs. Therefore, high potency opioids are the current standard of care in HA.

“Being granted an orphan drug designation for rofecoxib by FDA is an important regulatory milestone for Tremeau and affirms our strategy of providing non-opioid pain treatments for rare diseases like hemophilic arthropathy,” said Bradford C. Sippy, chief executive officer of Tremeau.

Sippy is a former Merck employee who helped with the recall of Vioxx and knew the final patent protecting the drug’s monopoly was expiring this fall.

When it stopped making Vioxx, Merck was facing thousands of lawsuits from people claiming the drug caused their heart attacks or strokes.

Merck’s own research showed the drug doubled those risks, but lawyers for patients claimed the company downplayed or concealed that. Merck initially fought the lawsuits but, in 2007, agreed to a $4.85 billion settlement.

If approved to treat HA, rofecoxib would carry a warning about the increased risk of heart attack and stroke associated with the drug.

Although the orphan designation for rofecoxib is a step toward FDA approval, Sippy said Tremeau must still raise $25 million or more to fund trials of the drug in hemophilia patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo by Steven Harbour

The US Food and Drug Administration (FDA) has granted orphan drug designation to rofecoxib (TRM-201) as a potential treatment for degenerative joint disease in hemophilia, also known as hemophilic arthropathy (HA).

Rofecoxib is a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) that was previously sold in the US under the name Vioxx.

Vioxx was FDA-approved to relieve the signs and symptoms of osteoarthritis, manage acute pain in adults, and treat primary dysmenorrhea.

Merck & Co. pulled Vioxx from the US market in 2004 due to safety concerns. The drug was shown to increase a person’s risk of cardiovascular events, including heart attack and stroke.

Now, Tremeau Pharmaceuticals, Inc., is working to bring rofecoxib back to market to treat patients with HA.

HA patients should not receive traditional NSAIDs due to their effects on platelet aggregation and the risk of gastrointestinal ulcers associated with these drugs. Therefore, high potency opioids are the current standard of care in HA.

“Being granted an orphan drug designation for rofecoxib by FDA is an important regulatory milestone for Tremeau and affirms our strategy of providing non-opioid pain treatments for rare diseases like hemophilic arthropathy,” said Bradford C. Sippy, chief executive officer of Tremeau.

Sippy is a former Merck employee who helped with the recall of Vioxx and knew the final patent protecting the drug’s monopoly was expiring this fall.

When it stopped making Vioxx, Merck was facing thousands of lawsuits from people claiming the drug caused their heart attacks or strokes.

Merck’s own research showed the drug doubled those risks, but lawyers for patients claimed the company downplayed or concealed that. Merck initially fought the lawsuits but, in 2007, agreed to a $4.85 billion settlement.

If approved to treat HA, rofecoxib would carry a warning about the increased risk of heart attack and stroke associated with the drug.

Although the orphan designation for rofecoxib is a step toward FDA approval, Sippy said Tremeau must still raise $25 million or more to fund trials of the drug in hemophilia patients.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

Photo from Novartis

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.

Photo from Novartis

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.

Photo from Novartis

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.

Photo from Business Wire

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.

Photo from Business Wire

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.

Photo from Business Wire

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.

acute lymphoblastic leukemia

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).

acute lymphoblastic leukemia

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).

acute lymphoblastic leukemia

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).

acute myeloid leukemia

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.”

acute myeloid leukemia

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.”

acute myeloid leukemia

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.”

Antihemophilic factor

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.

Antihemophilic factor

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.

Antihemophilic factor

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.

mycosis fungoides

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.

mycosis fungoides

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.

mycosis fungoides

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.

Photo by Chad McNeeley

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%).

Photo by Chad McNeeley

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%).

Photo by Chad McNeeley

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%).

Photo by Bill Branson

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).

Photo by Bill Branson

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).

Photo by Bill Branson

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).