Panel Backs Accelerated Approval of Brentuximab for Lymphomas

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.

SILVER SPRING, MD. – A Food and Drug Administration advisory panel voted 10-0 that accelerated approval should be granted to brentuximab vedotin as a treatment for two groups of patients with lymphomas that express the CD30 antigen.

If the agency accepts the two unanimous recommendations, brentuximab would be approved for patients with Hodgkin’s lymphoma that has relapsed after autologous stem cell transplant and for patients with relapsed or refractory systemic anaplastic large-cell lymphoma (ALCL).

The FDA is due to make a decision by Aug. 30. Seattle Genetics plans to market the new targeted agent, an antibody-drug conjugate, as Adcetris. It is developing the drug with Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada. Brentuximab is being reviewed for the same two indications in Europe.

The FDA’s Oncologic Drugs Advisory Committee reviewed and discussed the data on both indications in separate sessions at a meeting on July 14.

In a phase II single-arm study, 102 patients, aged 15-77 years (median 31 years), with relapsed or refractory progressive Hodgkin’s lymphoma and a previous autologous stem cell transplant, were treated with a median of nine cycles of brentuximab. The overall response rate was 75%, with a median duration of 6.7 months. The complete response rate was 34%, with a median duration of 20.5 months; and 40% of the patients treated achieved a partial remission.

Peripheral neuropathy was the most common adverse effect of treatment, affecting 47% of patients, according to Seattle Genetics, which is conducting a larger randomized double-blind phase III study to confirm the results of this smaller study.

In a nearly identical single-arm study of brentuximab in 58 patients with relapsed or refractory systemic ALCL, 57% had a complete remission, for a median of 13.2 months, and 29% had a partial remission. Together, these remissions accounted for an overall objective response rate of 86%, with a median duration of 12.6 months, the company reported. Median progression-free survival was 13 months.

Disease-related signs and symptoms, including cutaneous symptoms, resolved in a large proportion of patients with those symptoms. As with the Hodgkin’s lymphoma study, peripheral neuropathy was the most common treatment-related adverse event, affecting 48% of patients

ALCL is very rare, with only about 2,000 new cases diagnosed a year in the United States, and CD30 expression is universal, according to the company. It quotes the American Cancer Society as projecting more than 8,800 people will be diagnosed with Hodgkin’s lymphoma this year in the United States, with about 1,300 are expected to die of the disease.

FDA officials described brentuximab as "very promising." If it is approved, Seattle Genetics will be required to conduct studies to confirm the safety and efficacy of the treatment for the two indications, as a condition of accelerated approvals, before the drug can be fully approved.

Brentuximab is administered as an IV infusion every 3 weeks, at a dose of 1.8 mg/kg until the disease progresses or toxic effects become unacceptable.

The FDA usually follows the recommendations of its advisory panels. Panel members have been cleared of potential conflicts of interest related to the topic of the meeting, although occasionally they may be given a waiver, but none were given at this meeting.