CHMP supports new indication for venetoclax

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.

Photo courtesy of Abbvie

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that the European Commission (EC) approve a new indication for venetoclax (Venclyxto®).

AbbVie is seeking EC approval for venetoclax in combination with rituximab for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) who have received at least one prior therapy.

The EC typically makes an approval decision within 67 days of the CHMP’s opinion.

The EC’s decision will apply to the European Union, Norway, Iceland, and Liechtenstein.

Venetoclax is already EC-approved as monotherapy for:

• Adults with CLL who have 17p deletion or TP53 mutation and are unsuitable for or have failed treatment with a B-cell receptor pathway inhibitor
• Adults with CLL who do not have 17p deletion or TP53 mutation but have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.

The CHMP’s recommendation to approve venetoclax in combination with rituximab is supported by the phase 3 MURANO trial. Results from MURANO were published in The New England Journal of Medicine in March.

The trial included 389 CLL patients who were randomized to receive venetoclax plus rituximab (VEN+R) or bendamustine plus rituximab (B+R). The median follow-up was 23.8 months.

According to investigators, the median progression-free survival was not reached in the VEN+R arm and was 17.0 months in the B+R arm (hazard ratio, 0.17; P<0.0001).

According to an independent review committee, the median progression-free survival was not reached in the VEN+R arm and was 18.1 months in the B+R arm (hazard ratio, 0.20; P<0.0001).

Grade 3/4 adverse events (AEs) with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) included:

• Neutropenia (57.7% and 38.8%)
• Infections and infestations (17.5% and 21.8%)
• Anemia (10.8% and 13.8%)
• Thrombocytopenia (5.7% and 10.1%)
• Febrile neutropenia (3.6% and 9.6%)
• Pneumonia (5.2% and 8.0%)
• Infusion-related reaction (1.5% and 5.3%)
• Tumor lysis syndrome (3.1% and 1.1%)
• Hypotension (0% and 2.7%)
• Hyperglycemia (2.1% and 0%)
• Hypogammaglobulinemia (2.1% and 0%).

Serious AEs with at least a 2% difference in incidence between the treatment groups (in the VEN+R and B+R arms, respectively) were:

• Pneumonia (8.2% and 8.0%)
• Febrile neutropenia (3.6% and 8.5%)
• Pyrexia (2.6% and 6.9%)
• Anemia (1.5% and 2.7%)
• Infusion-related reaction (0.5% and 3.2%)
• Sepsis (0.5% and 2.1%)
• Tumor lysis syndrome (2.1% and 0.5%)
• Hypotension (0% and 2.7%).

Fatal AEs occurred in 5.2% of patients in the VEN+R arm and 5.9% in the B+R arm.

Fatal AEs in the VEN+R arm included pneumonia (n=3), sepsis (n=1), thrombocytopenia (n=1), cardiac failure (n=1), myocardial infarction (n=1), sudden cardiac death (n=1), colorectal cancer (n=1), status epilepticus (n=1), and acute respiratory failure (n=1). Two cases of pneumonia occurred in the setting of progression/Richter transformation.