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FDA approves ibrutinib as first-line CLL therapy
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved the BTK inhibitor ibrutinib (Imbruvica) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).
This means ibrutinib is now FDA-approved to treat CLL patients regardless of their treatment history, including patients with 17p deletion.
Ibrutinib is also FDA-approved to treat Waldenström’s macroglobulinemia, and the drug was granted accelerated approval to treat patients with mantle cell lymphoma who have received at least 1 prior therapy.
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc. For more details on the drug, see the full prescribing information, available at imbruvica.com.
RESONATE-2 trial
The latest FDA approval for ibrutinib is based on results from the phase 3 RESONATE-2 trial (PCYC-1115), which were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%). 
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved the BTK inhibitor ibrutinib (Imbruvica) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).
This means ibrutinib is now FDA-approved to treat CLL patients regardless of their treatment history, including patients with 17p deletion.
Ibrutinib is also FDA-approved to treat Waldenström’s macroglobulinemia, and the drug was granted accelerated approval to treat patients with mantle cell lymphoma who have received at least 1 prior therapy.
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc. For more details on the drug, see the full prescribing information, available at imbruvica.com.
RESONATE-2 trial
The latest FDA approval for ibrutinib is based on results from the phase 3 RESONATE-2 trial (PCYC-1115), which were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).
Photo courtesy of Janssen
The US Food and Drug Administration (FDA) has approved the BTK inhibitor ibrutinib (Imbruvica) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).
This means ibrutinib is now FDA-approved to treat CLL patients regardless of their treatment history, including patients with 17p deletion.
Ibrutinib is also FDA-approved to treat Waldenström’s macroglobulinemia, and the drug was granted accelerated approval to treat patients with mantle cell lymphoma who have received at least 1 prior therapy.
Ibrutinib is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company, and Janssen Biotech, Inc. For more details on the drug, see the full prescribing information, available at imbruvica.com.
RESONATE-2 trial
The latest FDA approval for ibrutinib is based on results from the phase 3 RESONATE-2 trial (PCYC-1115), which were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
RESONATE-2 enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma who were 65 or older.
Patients were randomized to receive ibrutinib (n=136) at 420 mg once a day until progression or unacceptable toxicity, or chlorambucil (n=133) on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in cycle 1 was 0.5 mg/kg and was increased based on tolerability in cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg.
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis.
Key secondary endpoints included overall response rate (based on the same iWCLL criteria), overall survival (OS), and safety.
Ibrutinib significantly prolonged PFS, as determined by the IRC, reducing the risk of progression or death by 84% compared to chlorambucil. The hazard ratio was 0.16 (P<0.001). The median PFS was not reached in the ibrutinib arm but was 18.9 months for the chlorambucil arm.
Ibrutinib significantly prolonged OS as well, although the median OS was not reached in either treatment arm. The OS rate at 24 months was 98% with ibrutinib and 85% with chlorambucil. The relative risk of death with ibrutinib was 84% lower than that with chlorambucil. The hazard ratio was 0.16 (P=0.001).
Ibrutinib was associated with a significantly higher IRC-assessed overall response rate compared to chlorambucil—82% and 35%, respectively (P<0.0001). Five patients (4%) in the ibrutinib arm achieved a complete response, as did 2 patients (2%) in the chlorambucil arm.
The median duration of treatment was 17.4 months in the ibrutinib arm and 7.1 months in the chlorambucil arm.
The most common adverse events of any grade—in the ibrutinib and chlorambucil arms, respectively—were diarrhea (42% and 17%), fatigue (30% and 38%), cough (22% and 15%), nausea (22% and 39%), peripheral edema (19% and 9%), dry eye (17% and 5%), arthralgia (16% and 7%), neutropenia (16% and 23%), and vomiting (13% and 20%).
Adverse events of grade 3 or higher—in the ibrutinib and chlorambucil arms, respectively—were neutropenia (10% and 18%), anemia (6% and 8%), hypertension (4% and 0%), pneumonia (4% and 2%), diarrhea (4% and 0%), maculopapular rash (3% and 2%), decreased platelet count (3% and 1%), abdominal pain (3% and 1%), hyponatremia (3% and 0%), thrombocytopenia (2% and 6%), febrile neutropenia (2% and 2%), upper respiratory tract infection (2% and 2%), pleural effusion (2% and 1%), cellulitis (2% and 0%), fatigue (1% and 5%), syncope (1% and 2%), and hemolytic anemia (0% and 2%).
Gene therapy granted orphan designation for hemophilia A
Image courtesy of NHLBI
The US Food and Drug Administration (FDA) has granted orphan designation to BMN 270, an investigational gene therapy, for the treatment of patients with hemophilia A.
BMN 270 is an adeno-associated virus-factor VIII (FVIII) vector designed to restore FVIII plasma concentrations in these patients.
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
BMN 270 is under development by BioMarin Pharmaceutical Inc.
BioMarin is conducting a phase 1/2 study to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
Researchers are assessing the safety of a single infusion of BMN 270 and the change in FVIII expression level from baseline to 16 weeks after infusion.
The group is also assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses.
Patients will be monitored for safety and durability of effect for 5 years. BioMarin plans to provide an update on this trial in April.
Image courtesy of NHLBI
The US Food and Drug Administration (FDA) has granted orphan designation to BMN 270, an investigational gene therapy, for the treatment of patients with hemophilia A.
BMN 270 is an adeno-associated virus-factor VIII (FVIII) vector designed to restore FVIII plasma concentrations in these patients.
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
BMN 270 is under development by BioMarin Pharmaceutical Inc.
BioMarin is conducting a phase 1/2 study to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
Researchers are assessing the safety of a single infusion of BMN 270 and the change in FVIII expression level from baseline to 16 weeks after infusion.
The group is also assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses.
Patients will be monitored for safety and durability of effect for 5 years. BioMarin plans to provide an update on this trial in April.
Image courtesy of NHLBI
The US Food and Drug Administration (FDA) has granted orphan designation to BMN 270, an investigational gene therapy, for the treatment of patients with hemophilia A.
BMN 270 is an adeno-associated virus-factor VIII (FVIII) vector designed to restore FVIII plasma concentrations in these patients.
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.
The designation provides the drug’s sponsor with various development incentives, including opportunities to apply for research-related tax credits and grant funding, assistance in designing clinical trials, and 7 years of US market exclusivity if the drug is approved.
BMN 270 is under development by BioMarin Pharmaceutical Inc.
BioMarin is conducting a phase 1/2 study to evaluate the safety and efficacy of BMN 270 in up to 12 patients with severe hemophilia A.
Researchers are assessing the safety of a single infusion of BMN 270 and the change in FVIII expression level from baseline to 16 weeks after infusion.
The group is also assessing the impact of BMN 270 on the frequency of FVIII replacement therapy, the number of bleeding episodes requiring treatment, and any potential immune responses.
Patients will be monitored for safety and durability of effect for 5 years. BioMarin plans to provide an update on this trial in April.
EC approves drug for iron-deficiency anemia in IBD
The European Commission (EC) has granted marketing authorization for ferric maltol (Feraccru) to treat iron-deficiency anemia in adults with inflammatory bowel disease (IBD).
The product can now be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The company developing the drug, Shield Therapeutics, said it will begin a roll-out of commercialization in the coming months.
Feraccru contains iron in a stable ferric state as a complex with a trimaltol ligand—ferric maltol. It is formulated as 30 mg of ferric iron in a hard gelatin capsule.
The complex is designed to provide iron for uptake across the intestinal wall and transfer to the iron transport and storage proteins—transferrin and ferritin, respectively. Feraccru dissociates on uptake from the gastrointestinal tract, and ferric maltol itself does not appear to enter the systemic circulation.
Phase 3 trials
The EC’s approval of ferric maltol is based on results of 2 phase 3 studies—AEGIS 1 and AEGIS 2. The results of these studies were published in Inflammatory Bowel Diseases in March 2015.
Together, the trials included 128 adult patients with IBD (ulcerative colitis and Crohn’s disease), iron-deficiency anemia, and recorded intolerance of ferrous sulphate. They were randomized to receive either 30 mg of ferric maltol twice a day or a matched placebo capsule for 12 weeks.
The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline to week 12. The mean improvement in Hb in the ferric maltol group compared to the placebo group was 2.25 g/dL (P<0.0001).
The absolute mean Hb concentration improved from 11.00 g/dL at baseline to 13.20 g/dL at week 12 in the ferric maltol group. In the placebo group, the mean Hb values were similar at baseline and week 12—11.10 g/dL and 11.20 g/dL, respectively.
The incidence of treatment-emergent adverse events (AEs) was 58% in the ferric maltol group and 72% in the placebo group. However, not all of these events were considered treatment-related.
AEs that were considered treatment-related occurred in 25% of ferric maltol-treated patients and 11.7% of placebo-treated patients. The most common treatment-related AEs in the ferric maltol group were abdominal pain, constipation, and flatulence—each occurring in 6.7% of patients.
“The phase 3 clinical studies clearly demonstrated Feraccru’s effectiveness,” said Andreas Stallmach, MD, of University Clinic Jena in Germany.
“[T]his pan-European marketing authorization gives treating physicians like myself the opportunity to fulfill an important and currently unmet need for patients who are unable to tolerate other oral products, as Feraccru could provide an oral alternative to intravenous iron infusion.’’
The European Commission (EC) has granted marketing authorization for ferric maltol (Feraccru) to treat iron-deficiency anemia in adults with inflammatory bowel disease (IBD).
The product can now be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The company developing the drug, Shield Therapeutics, said it will begin a roll-out of commercialization in the coming months.
Feraccru contains iron in a stable ferric state as a complex with a trimaltol ligand—ferric maltol. It is formulated as 30 mg of ferric iron in a hard gelatin capsule.
The complex is designed to provide iron for uptake across the intestinal wall and transfer to the iron transport and storage proteins—transferrin and ferritin, respectively. Feraccru dissociates on uptake from the gastrointestinal tract, and ferric maltol itself does not appear to enter the systemic circulation.
Phase 3 trials
The EC’s approval of ferric maltol is based on results of 2 phase 3 studies—AEGIS 1 and AEGIS 2. The results of these studies were published in Inflammatory Bowel Diseases in March 2015.
Together, the trials included 128 adult patients with IBD (ulcerative colitis and Crohn’s disease), iron-deficiency anemia, and recorded intolerance of ferrous sulphate. They were randomized to receive either 30 mg of ferric maltol twice a day or a matched placebo capsule for 12 weeks.
The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline to week 12. The mean improvement in Hb in the ferric maltol group compared to the placebo group was 2.25 g/dL (P<0.0001).
The absolute mean Hb concentration improved from 11.00 g/dL at baseline to 13.20 g/dL at week 12 in the ferric maltol group. In the placebo group, the mean Hb values were similar at baseline and week 12—11.10 g/dL and 11.20 g/dL, respectively.
The incidence of treatment-emergent adverse events (AEs) was 58% in the ferric maltol group and 72% in the placebo group. However, not all of these events were considered treatment-related.
AEs that were considered treatment-related occurred in 25% of ferric maltol-treated patients and 11.7% of placebo-treated patients. The most common treatment-related AEs in the ferric maltol group were abdominal pain, constipation, and flatulence—each occurring in 6.7% of patients.
“The phase 3 clinical studies clearly demonstrated Feraccru’s effectiveness,” said Andreas Stallmach, MD, of University Clinic Jena in Germany.
“[T]his pan-European marketing authorization gives treating physicians like myself the opportunity to fulfill an important and currently unmet need for patients who are unable to tolerate other oral products, as Feraccru could provide an oral alternative to intravenous iron infusion.’’
The European Commission (EC) has granted marketing authorization for ferric maltol (Feraccru) to treat iron-deficiency anemia in adults with inflammatory bowel disease (IBD).
The product can now be marketed for this indication in the 28 member countries of the European Union, as well as Iceland, Liechtenstein, and Norway.
The company developing the drug, Shield Therapeutics, said it will begin a roll-out of commercialization in the coming months.
Feraccru contains iron in a stable ferric state as a complex with a trimaltol ligand—ferric maltol. It is formulated as 30 mg of ferric iron in a hard gelatin capsule.
The complex is designed to provide iron for uptake across the intestinal wall and transfer to the iron transport and storage proteins—transferrin and ferritin, respectively. Feraccru dissociates on uptake from the gastrointestinal tract, and ferric maltol itself does not appear to enter the systemic circulation.
Phase 3 trials
The EC’s approval of ferric maltol is based on results of 2 phase 3 studies—AEGIS 1 and AEGIS 2. The results of these studies were published in Inflammatory Bowel Diseases in March 2015.
Together, the trials included 128 adult patients with IBD (ulcerative colitis and Crohn’s disease), iron-deficiency anemia, and recorded intolerance of ferrous sulphate. They were randomized to receive either 30 mg of ferric maltol twice a day or a matched placebo capsule for 12 weeks.
The primary efficacy endpoint was the change in hemoglobin (Hb) levels from baseline to week 12. The mean improvement in Hb in the ferric maltol group compared to the placebo group was 2.25 g/dL (P<0.0001).
The absolute mean Hb concentration improved from 11.00 g/dL at baseline to 13.20 g/dL at week 12 in the ferric maltol group. In the placebo group, the mean Hb values were similar at baseline and week 12—11.10 g/dL and 11.20 g/dL, respectively.
The incidence of treatment-emergent adverse events (AEs) was 58% in the ferric maltol group and 72% in the placebo group. However, not all of these events were considered treatment-related.
AEs that were considered treatment-related occurred in 25% of ferric maltol-treated patients and 11.7% of placebo-treated patients. The most common treatment-related AEs in the ferric maltol group were abdominal pain, constipation, and flatulence—each occurring in 6.7% of patients.
“The phase 3 clinical studies clearly demonstrated Feraccru’s effectiveness,” said Andreas Stallmach, MD, of University Clinic Jena in Germany.
“[T]his pan-European marketing authorization gives treating physicians like myself the opportunity to fulfill an important and currently unmet need for patients who are unable to tolerate other oral products, as Feraccru could provide an oral alternative to intravenous iron infusion.’’
Drug granted orphan designation for hemolytic anemia
The European Commission (EC) has granted orphan drug designation for TNT009 to treat autoimmune hemolytic anemia, including cold agglutinin disease.
TNT009 is a monoclonal antibody that selectively inhibits the classical complement pathway by targeting C1s, a serine protease within the C1-complex in the complement pathway.
The drug thereby prevents downstream disease processes involving phagocytosis, inflammation, and cell lysis.
TNT009 is being developed by True North Therapeutics.
The drug is currently in development for the treatment of autoimmune hemolytic anemia, which is characterized by the premature destruction of healthy red blood cells by autoantibodies.
In cold agglutinin disease, this destruction of red blood cells results in anemia, fatigue, and potentially fatal thrombosis.
TNT009 is also being evaluated in patients with bullous pemphigoid and end-stage renal disease.
Top-line results from a phase 1b trial of TNT009 are expected in mid-2016.
About orphan designation
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
The European Commission (EC) has granted orphan drug designation for TNT009 to treat autoimmune hemolytic anemia, including cold agglutinin disease.
TNT009 is a monoclonal antibody that selectively inhibits the classical complement pathway by targeting C1s, a serine protease within the C1-complex in the complement pathway.
The drug thereby prevents downstream disease processes involving phagocytosis, inflammation, and cell lysis.
TNT009 is being developed by True North Therapeutics.
The drug is currently in development for the treatment of autoimmune hemolytic anemia, which is characterized by the premature destruction of healthy red blood cells by autoantibodies.
In cold agglutinin disease, this destruction of red blood cells results in anemia, fatigue, and potentially fatal thrombosis.
TNT009 is also being evaluated in patients with bullous pemphigoid and end-stage renal disease.
Top-line results from a phase 1b trial of TNT009 are expected in mid-2016.
About orphan designation
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
The European Commission (EC) has granted orphan drug designation for TNT009 to treat autoimmune hemolytic anemia, including cold agglutinin disease.
TNT009 is a monoclonal antibody that selectively inhibits the classical complement pathway by targeting C1s, a serine protease within the C1-complex in the complement pathway.
The drug thereby prevents downstream disease processes involving phagocytosis, inflammation, and cell lysis.
TNT009 is being developed by True North Therapeutics.
The drug is currently in development for the treatment of autoimmune hemolytic anemia, which is characterized by the premature destruction of healthy red blood cells by autoantibodies.
In cold agglutinin disease, this destruction of red blood cells results in anemia, fatigue, and potentially fatal thrombosis.
TNT009 is also being evaluated in patients with bullous pemphigoid and end-stage renal disease.
Top-line results from a phase 1b trial of TNT009 are expected in mid-2016.
About orphan designation
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
EC grants venetoclax orphan designation for AML
The European Commission has granted orphan drug designation for the oral BCL-2 inhibitor venetoclax to treat acute myeloid leukemia (AML).
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the
European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
Phase 2 study
Results from a phase 2 study of venetoclax in AML were presented at ASH 2014. At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.
The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 achieving a CR with incomplete count recovery (CRi).
The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.
The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.
Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.
Grade 3/4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.
The European Commission has granted orphan drug designation for the oral BCL-2 inhibitor venetoclax to treat acute myeloid leukemia (AML).
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the
European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
Phase 2 study
Results from a phase 2 study of venetoclax in AML were presented at ASH 2014. At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.
The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 achieving a CR with incomplete count recovery (CRi).
The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.
The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.
Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.
Grade 3/4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.
The European Commission has granted orphan drug designation for the oral BCL-2 inhibitor venetoclax to treat acute myeloid leukemia (AML).
The EC grants orphan designation to products intended to treat, prevent, or diagnose a life-threatening condition affecting up to 5 in 10,000 people in the
European Union. The product must provide significant benefit to those affected by the condition.
Orphan drug designation from the EC provides companies with certain development incentives, including protocol assistance, a type of scientific advice specific for orphan drugs, and 10 years of market exclusivity once the drug is on the market.
Venetoclax is being developed by AbbVie in partnership with Genentech and Roche.
Phase 2 study
Results from a phase 2 study of venetoclax in AML were presented at ASH 2014. At that time, the trial had enrolled 32 patients, 30 of whom had relapsed or refractory disease. Patients had a median age of 71 (range, 19 to 84), and half were male.
The overall response rate was 15.5%, with 1 patient achieving a complete response (CR) and 4 achieving a CR with incomplete count recovery (CRi).
The researchers noted that 3 of the patients who had a CR/CRi had IDH mutations. Two of these patients also achieved minimal residual disease negativity.
The median bone marrow blast count in evaluable patients decreased 36% after treatment, and 6 patients (19%) had at least a 50% reduction in bone marrow blasts.
Common adverse events following treatment (occurring in at least 25% of patients) included nausea, diarrhea, fatigue, neutropenia, and vomiting.
Grade 3/4 adverse events (occurring in 3 or more patients) included febrile neutropenia, anemia, and pneumonia. No patient died as a result of treatment-related adverse events.
CHMP recommends fusion protein for hemophilia B
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that albutrepenonacog alfa (Idelvion) receive marketing authorization to treat patients with hemophilia B.
Albutrepenonacog alfa is a recombinant fusion protein linking coagulation factor IX with albumin.
The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice.
In 2010, the European Commission granted albutrepenonacog alfa orphan designation as a treatment for hemophilia B.
Albutrepenonacog alfa is being developed by CSL Behring. The product is approved for use in Canada. Regulatory agencies in the US, Australia, Switzerland, and Japan are reviewing applications for the drug.
Phase 3 trial
The CHMP’s recommendation to approve albutrepenonacog alfa is based on the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks, followed by a 7-, 10- or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that albutrepenonacog alfa (Idelvion) receive marketing authorization to treat patients with hemophilia B.
Albutrepenonacog alfa is a recombinant fusion protein linking coagulation factor IX with albumin.
The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice.
In 2010, the European Commission granted albutrepenonacog alfa orphan designation as a treatment for hemophilia B.
Albutrepenonacog alfa is being developed by CSL Behring. The product is approved for use in Canada. Regulatory agencies in the US, Australia, Switzerland, and Japan are reviewing applications for the drug.
Phase 3 trial
The CHMP’s recommendation to approve albutrepenonacog alfa is based on the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks, followed by a 7-, 10- or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that albutrepenonacog alfa (Idelvion) receive marketing authorization to treat patients with hemophilia B.
Albutrepenonacog alfa is a recombinant fusion protein linking coagulation factor IX with albumin.
The CHMP’s recommendation will be reviewed by the European Commission, which usually follows the CHMP’s advice.
In 2010, the European Commission granted albutrepenonacog alfa orphan designation as a treatment for hemophilia B.
Albutrepenonacog alfa is being developed by CSL Behring. The product is approved for use in Canada. Regulatory agencies in the US, Australia, Switzerland, and Japan are reviewing applications for the drug.
Phase 3 trial
The CHMP’s recommendation to approve albutrepenonacog alfa is based on the PROLONG-9FP clinical development program. PROLONG-9FP includes phase 1, 2, and 3 studies evaluating the safety and efficacy of albutrepenonacog alfa in adults and children (ages 1 to 61) with hemophilia B.
Data from the phase 3 study were recently published in Blood. This study included 63 previously treated male patients with severe hemophilia B. They had a mean age of 33 (range, 12 to 61).
The patients were divided into 2 groups. Group 1 (n=40) received routine prophylaxis with albutrepenonacog alfa once every 7 days for 26 weeks, followed by a 7-, 10- or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively.
Group 2 received on-demand treatment with albutrepenonacog alfa for bleeding episodes for 26 weeks (n=23) and then switched to a 7-day prophylaxis regimen for a mean of 45 weeks (n=19).
The median annualized bleeding rate (ABR) was 2.0 in the prophylaxis arm (group 1) and 23.5 in the on-demand treatment arm (group 2). The median spontaneous ABRs were 0.0 and 17.0, respectively.
For patients in group 2, there was a significant reduction in median ABRs when patients switched from on-demand treatment to prophylaxis—19.22 and 1.58, respectively (P<0.0001). And there was a significant reduction in median spontaneous ABRs—15.43 and 0.00, respectively (P<0.0001).
Overall, 98.6% of bleeding episodes were treated successfully, including 93.6% that were treated with a single injection of albutrepenonacog alfa.
None of the patients developed inhibitors or experienced thromboembolic events, anaphylaxis, or life-threatening adverse events (AEs).
There were 347 treatment-emergent AEs reported in 54 (85.7%) patients. The most common were nasopharyngitis (25.4%), headache (23.8%), arthralgia (4.3%), and influenza (11.1%).
Eleven mild/moderate AEs in 5 patients (7.9%) were considered possibly related to albutrepenonacog alfa. Two patients discontinued treatment due to AEs—1 with hypersensitivity and 1 with headache.
FDA approves obinutuzumab for FL
The US Food and Drug Administration (FDA) has approved obinutuzumab (Gazyva) for certain patients with previously treated follicular lymphoma (FL).
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug was previously approved by the FDA for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Now, obinutuzumab is approved for use in combination with bendamustine, followed by obinutuzumab alone, to treat patients with FL who did not respond to a rituximab-containing regimen or whose FL returned after such treatment.
The recommended dose and schedule for the regimen is:
- Obinutuzumab at 1000 mg by intravenous infusion on days 1, 8, and 15 of cycle 1; on day 1 of cycles 2-6 (28-day cycles); then every 2 months for 2 years.
- Bendamustine at 90 mg/m2 by intravenous infusion on days 1 and 2 of cycles 1-6.
Full prescribing information for obinutuzumab is available on the FDA website or at www.Gazyva.com.
Phase 3 study
The approval for obinutuzumab in FL is based on results from the phase 3 GADOLIN study. The trial included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS as assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
Best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
About obinutuzumab
Obinutuzumab is being studied in a large clinical program, including the phase 3 GOYA and GALLIUM studies.
In GOYA, researchers are comparing obinutuzumab head-to-head with rituximab plus CHOP chemotherapy in first-line diffuse large B-cell lymphoma. In GALLIUM, researchers are comparing obinutuzumab plus chemotherapy head-to-head with rituximab plus chemotherapy in first-line indolent non-Hodgkin lymphoma.
Additional combination studies investigating obinutuzumab with other approved or investigational medicines, including cancer immunotherapies and small-molecule inhibitors, are planned or underway across a range of blood cancers.
Obinutuzumab was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the US, obinutuzumab is part of a collaboration between Genentech and Biogen.
Genentech has a patient assistance program, Genentech Access Solutions, that can help qualifying patients access obinutuzumab and other Genentech medications.
The program is designed to help people navigate the access and reimbursement process and provide assistance to eligible patients in the US who are uninsured or cannot afford the out-of-pocket costs for their medicine. For more information, visit www.Genentech-Access.com.
The US Food and Drug Administration (FDA) has approved obinutuzumab (Gazyva) for certain patients with previously treated follicular lymphoma (FL).
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug was previously approved by the FDA for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Now, obinutuzumab is approved for use in combination with bendamustine, followed by obinutuzumab alone, to treat patients with FL who did not respond to a rituximab-containing regimen or whose FL returned after such treatment.
The recommended dose and schedule for the regimen is:
- Obinutuzumab at 1000 mg by intravenous infusion on days 1, 8, and 15 of cycle 1; on day 1 of cycles 2-6 (28-day cycles); then every 2 months for 2 years.
- Bendamustine at 90 mg/m2 by intravenous infusion on days 1 and 2 of cycles 1-6.
Full prescribing information for obinutuzumab is available on the FDA website or at www.Gazyva.com.
Phase 3 study
The approval for obinutuzumab in FL is based on results from the phase 3 GADOLIN study. The trial included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS as assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
Best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
About obinutuzumab
Obinutuzumab is being studied in a large clinical program, including the phase 3 GOYA and GALLIUM studies.
In GOYA, researchers are comparing obinutuzumab head-to-head with rituximab plus CHOP chemotherapy in first-line diffuse large B-cell lymphoma. In GALLIUM, researchers are comparing obinutuzumab plus chemotherapy head-to-head with rituximab plus chemotherapy in first-line indolent non-Hodgkin lymphoma.
Additional combination studies investigating obinutuzumab with other approved or investigational medicines, including cancer immunotherapies and small-molecule inhibitors, are planned or underway across a range of blood cancers.
Obinutuzumab was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the US, obinutuzumab is part of a collaboration between Genentech and Biogen.
Genentech has a patient assistance program, Genentech Access Solutions, that can help qualifying patients access obinutuzumab and other Genentech medications.
The program is designed to help people navigate the access and reimbursement process and provide assistance to eligible patients in the US who are uninsured or cannot afford the out-of-pocket costs for their medicine. For more information, visit www.Genentech-Access.com.
The US Food and Drug Administration (FDA) has approved obinutuzumab (Gazyva) for certain patients with previously treated follicular lymphoma (FL).
Obinutuzumab is a glycoengineered, humanized, monoclonal antibody that selectively binds to the extracellular domain of the CD20 antigen on B cells.
The drug was previously approved by the FDA for use in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia.
Now, obinutuzumab is approved for use in combination with bendamustine, followed by obinutuzumab alone, to treat patients with FL who did not respond to a rituximab-containing regimen or whose FL returned after such treatment.
The recommended dose and schedule for the regimen is:
- Obinutuzumab at 1000 mg by intravenous infusion on days 1, 8, and 15 of cycle 1; on day 1 of cycles 2-6 (28-day cycles); then every 2 months for 2 years.
- Bendamustine at 90 mg/m2 by intravenous infusion on days 1 and 2 of cycles 1-6.
Full prescribing information for obinutuzumab is available on the FDA website or at www.Gazyva.com.
Phase 3 study
The approval for obinutuzumab in FL is based on results from the phase 3 GADOLIN study. The trial included 413 patients with rituximab-refractory non-Hodgkin lymphoma, including 321 patients with FL, 46 with marginal zone lymphoma, and 28 with small lymphocytic lymphoma.
The patients were randomized to receive bendamustine alone (control arm) or a combination of bendamustine and obinutuzumab followed by obinutuzumab maintenance (every 2 months for 2 years or until progression).
The primary endpoint of the study was progression-free survival (PFS), as assessed by an independent review committee (IRC). The secondary endpoints were PFS as assessed by investigator review, best overall response, complete response (CR), partial response (PR), duration of response, overall survival, and safety profile.
Among patients with FL, the obinutuzumab regimen improved PFS compared to bendamustine alone, as assessed by IRC (hazard ratio [HR]=0.48, P<0.0001). The median PFS was not reached in patients receiving the obinutuzumab regimen but was 13.8 months in those receiving bendamustine alone.
Investigator-assessed PFS was consistent with IRC-assessed PFS. Investigators said the median PFS with the obinutuzumab regimen was more than double that with bendamustine alone—29.2 months vs 13.7 months (HR=0.48, P<0.0001).
Best overall response for patients receiving the obinutuzumab regimen was 78.7% (15.5% CR, 63.2% PR), compared to 74.7% for those receiving bendamustine alone (18.7% CR, 56% PR), as assessed by the IRC.
The median duration of response was not reached for patients receiving the obinutuzumab regimen and was 11.6 months for those receiving bendamustine alone.
The median overall survival has not yet been reached in either study arm.
The most common grade 3/4 adverse events observed in patients receiving the obinutuzumab regimen were neutropenia (33%), infusion reactions (11%), and thrombocytopenia (10%).
The most common adverse events of any grade were infusion reactions (69%), neutropenia (35%), nausea (54%), fatigue (39%), cough (26%), diarrhea (27%), constipation (19%), fever (18%), thrombocytopenia (15%), vomiting (22%), upper respiratory tract infection (13%), decreased appetite (18%), joint or muscle pain (12%), sinusitis (12%), anemia (12%), general weakness (11%), and urinary tract infection (10%).
About obinutuzumab
Obinutuzumab is being studied in a large clinical program, including the phase 3 GOYA and GALLIUM studies.
In GOYA, researchers are comparing obinutuzumab head-to-head with rituximab plus CHOP chemotherapy in first-line diffuse large B-cell lymphoma. In GALLIUM, researchers are comparing obinutuzumab plus chemotherapy head-to-head with rituximab plus chemotherapy in first-line indolent non-Hodgkin lymphoma.
Additional combination studies investigating obinutuzumab with other approved or investigational medicines, including cancer immunotherapies and small-molecule inhibitors, are planned or underway across a range of blood cancers.
Obinutuzumab was discovered by Roche Glycart AG, a wholly owned, independent research unit of Roche. In the US, obinutuzumab is part of a collaboration between Genentech and Biogen.
Genentech has a patient assistance program, Genentech Access Solutions, that can help qualifying patients access obinutuzumab and other Genentech medications.
The program is designed to help people navigate the access and reimbursement process and provide assistance to eligible patients in the US who are uninsured or cannot afford the out-of-pocket costs for their medicine. For more information, visit www.Genentech-Access.com.
Orphan designation recommended for BTK inhibitor
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.
The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.
The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.
To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.
Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.
About acalabrutinib
Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.
Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).
Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.
At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.
The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).
Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).
The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.
The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.
The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.
The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.
To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.
Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.
About acalabrutinib
Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.
Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).
Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.
At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.
The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).
Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).
The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.
The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for the second-generation BTK inhibitor acalabrutinib (ACP-196) for 3 indications.
The COMP is recommending the drug receive orphan designation as a treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma, and Waldenström’s macroglobulinemia.
The COMP adopts an opinion on orphan drug designation, and that opinion is submitted to the European Commission (EC) for endorsement.
To be granted orphan designation by the EC, a medicine must be intended for the treatment, prevention, or diagnosis of a disease that is life-threatening and has a prevalence of up to 5 in 10,000 in the European Union. Additionally, the medicine must aim to provide significant benefit to those affected by the condition.
Orphan designation provides companies with development and market exclusivity incentives for designated compounds and medicines.
About acalabrutinib
Acalabrutinib is under development by AstraZeneca and Acerta Pharma BV. The drug is currently being evaluated in trials of patients with CLL/SLL, mantle cell lymphoma, Waldentröm’s macroglobulinemia, and a range of other hematologic malignancies and solid tumor cancers.
Data from a phase 1/2 trial of acalabrutinib in CLL were presented at the 2015 ASH Annual Meeting and simultaneously published in NEJM.
The researchers reported on 61 patients with relapsed CLL who had a median age of 62 (range, 44-84) and a median of 3 prior therapies (range, 1-13).
Patients enrolled in the phase 1 portion of the study received escalating doses of acalabrutinib, with a maximum dose of 400 mg once daily. Patients involved in the phase 2 portion of the study were treated with a 100 mg dose twice daily.
At a median follow-up of 14.3 months (range, 0.5 to 20), 53 patients were still receiving treatment.
The most common adverse events of all grades (occurring in at least 20% of patients) were headache (43%), diarrhea (39%), increased weight (26%), pyrexia (23%), upper respiratory tract infection (23%), fatigue (21%), peripheral edema (21%), hypertension (20%), and nausea (20%).
Grade 3/4 adverse events included diarrhea (2%), increased weight (2%), pyrexia (3%), fatigue (3%), hypertension (7%), and arthralgia (2%).
The overall response rate among the 60 evaluable patients was 95%. This included partial responses in 85% of patients and partial responses with lymphocytosis in 10%. The rate of stable disease was 5%.
The researchers noted that responses occurred in all dosing cohorts, and the response rate increased over time.
FDA investigates issues with rivaroxaban trial
The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.
ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.
According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.
The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.
The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.
Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.
However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.
The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.
The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.
ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.
According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.
The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.
The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.
Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.
However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.
The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.
The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.
ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.
According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.
The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.
Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.
However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.
The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.
Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.
Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.
However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.
The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.
Adjunct T-cell therapy granted orphan designation
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.
The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.
The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).
BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.
The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.
This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.
Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.
The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.
BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.
About orphan designation
The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.
Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.