Health Canada approves SC rituximab for CLL

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).

Syringe

Health Canada has approved a subcutaneous (SC) formulation of rituximab (Rituxan®) to treat patients with chronic lymphocytic leukemia (CLL).

The product is now approved for use in combination with fludarabine and cyclophosphamide to treat patients with previously treated or untreated CLL, Binet Stage B or C.

The SC formulation is intended to provide a more convenient delivery method than intravenous (IV) rituximab. The SC formulation enables administration of the drug in large volumes under the skin.

“The approval of Rituxan SC is exciting news and a meaningful advancement for those living with CLL, as intravenous treatments can take around 4 hours to receive, requiring patients to spend up to a half day sitting in the chemo suite,” said Robin Markowitz, chief executive officer of Lymphoma Canada.

“The administration of Rituxan SC only takes 7 minutes, giving patients valuable time back in their day.”

SAWYER study

Health Canada’s approval of SC rituximab is based on data from the phase 1b SAWYER study. This randomized study was conducted in patients with previously untreated CLL to investigate the pharmacokinetic profile, safety, and efficacy of SC rituximab in combination with chemotherapy.

Results from this study were published in The Lancet Haematology in March 2016.

The trial included 176 patients who were randomized to receive SC rituximab (1600 mg, n=88) or IV rituximab (500 mg/m², n=88) on day 1 from cycles 2 to 6. In cycle 1, both groups received IV rituximab (375 mg/m²) on day 0.

All patients also received fludarabine (IV 25 mg/m² on days 1-3 of all cycles or orally at either 25 mg/m² on days 1-5 of all cycles or 30-40 mg/m² on days 1-3 of all cycles) and cyclophosphamide (IV at 250 mg/m² on days 1-3 of all cycles or orally at either 150 mg/m² on days 1-5 of all cycles or 200-250 mg/m² on days 1-3 of all cycles) every 4 weeks for up to 6 cycles.

The primary endpoint was pharmacokinetic noninferiority of SC to IV rituximab assessed at cycle 5. At that time, the geometric mean trough serum concentration in the SC rituximab arm was noninferior to that in the IV arm—97.5 µg/mL and 61.5 µg/mL, respectively—with an adjusted geometric mean ratio of 1.53 (90% CI, 1.27 to 1.85).

Safety was a secondary endpoint, and efficacy was an exploratory endpoint.

The overall response rate was 85% in the SC arm and 81% in the IV arm. Complete response rates were 26% and 33%, respectively.

Rates of adverse events (AEs) were 96% in the SC arm and 91% in the IV arm. Rates of grade 3 or higher AEs were 69% and 71%, respectively, and rates of serious AEs were 29% and 33%, respectively.

The most common serious AE overall was febrile neutropenia, which occurred in 11% of patients in the SC arm and 4% in the IV arm.

The most common AEs of any grade (occurring in >20% of patients in either arm) were:

• Neutropenia—65% with SC and 58% with IV
• Thrombocytopenia—24% with SC and 26% with IV
• Anemia—13% with SC and 24% with IV
• Nausea—38% with SC and 35% with IV
• Vomiting—21% with SC and 22% with IV
• Pyrexia—32% with SC and 25% with IV
• Injection-site erythema—26% with SC and 0% with IV.

Local cutaneous reactions were reported in 42% of patients in the SC arm. The most common of these were injection-site erythema (26%) and injection-site pain (16%).