FDA Approves Brentuximab for Two Lymphomas

The Food and Drug Administration on Aug. 19 approved brentuximab, a CD30-directed antibody drug-conjugate, for the treatment of Hodgkin’s lymphoma and systemic anaplastic large-cell lymphoma, after other treatments have failed.

Specifically, brentuximab was approved for the treatment of patients with Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It is the first new treatment approved for HL by the FDA since 1977, according to the FDA statement. The indications are based on response rates, and there are no available data that show "improvement in patient reported outcomes or survival" with treatment, according to the prescribing information.

The FDA also approved brentuximab for patients with systemic anaplastic large-cell lymphoma (ALCL), a rare form of lymphoma, after failure of at least one prior multiagent chemotherapy regimen. It is the first treatment approved for this rare lymphoma; approximately 2,000 new cases are diagnosed yearly in the United States.

Both types of lymphomas express the CD30 antigen. Brentuximab is a combination of an anti-CD30 antibody and a drug, monomethyl auristatin E (MMAE), a microtubule disrupting agent. The antibody directs the drug to C30-expressing tumor cells, where it is released.

Brentuximab is administered intravenously every 3 weeks; it will be marketed in the United States as Adcetris by Seattle Genetics. It will be available the week of Aug. 22, according to a company spokesperson.

The product was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug for a serious disease based on data showing the drug is effective on a surrogate end point that is "reasonably likely" to predict clinical benefit. Accelerated approvals provide patients with access to promising treatments, but companies are required to provide confirmatory clinical data in order for the drug to be converted to a full approval and remain on the market.

"Early clinical data suggest that patients who received Adcetris for Hodgkin’s lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

In a study of 102 patients with HL treated with brentuximab, 73% of the patients had either a complete or partial response to treatment. In a similarly designed study of 58 patients with ALCL, 86% achieved a partial or complete response to treatment. Neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper-respiratory infection, diarrhea, fever, cough, vomiting, and thrombocytopenia were among the most common adverse effects associated with treatment, according to the FDA.

At a meeting in July, an FDA advisory panel recommended the accelerated approval of both indications.

Brentuximab is under review for the same indications in Europe; a decision on approval is expected in the first half of 2012, according to a spokesperson for Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada.

The Food and Drug Administration on Aug. 19 approved brentuximab, a CD30-directed antibody drug-conjugate, for the treatment of Hodgkin’s lymphoma and systemic anaplastic large-cell lymphoma, after other treatments have failed.

Specifically, brentuximab was approved for the treatment of patients with Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It is the first new treatment approved for HL by the FDA since 1977, according to the FDA statement. The indications are based on response rates, and there are no available data that show "improvement in patient reported outcomes or survival" with treatment, according to the prescribing information.

The FDA also approved brentuximab for patients with systemic anaplastic large-cell lymphoma (ALCL), a rare form of lymphoma, after failure of at least one prior multiagent chemotherapy regimen. It is the first treatment approved for this rare lymphoma; approximately 2,000 new cases are diagnosed yearly in the United States.

Both types of lymphomas express the CD30 antigen. Brentuximab is a combination of an anti-CD30 antibody and a drug, monomethyl auristatin E (MMAE), a microtubule disrupting agent. The antibody directs the drug to C30-expressing tumor cells, where it is released.

Brentuximab is administered intravenously every 3 weeks; it will be marketed in the United States as Adcetris by Seattle Genetics. It will be available the week of Aug. 22, according to a company spokesperson.

The product was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug for a serious disease based on data showing the drug is effective on a surrogate end point that is "reasonably likely" to predict clinical benefit. Accelerated approvals provide patients with access to promising treatments, but companies are required to provide confirmatory clinical data in order for the drug to be converted to a full approval and remain on the market.

"Early clinical data suggest that patients who received Adcetris for Hodgkin’s lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

In a study of 102 patients with HL treated with brentuximab, 73% of the patients had either a complete or partial response to treatment. In a similarly designed study of 58 patients with ALCL, 86% achieved a partial or complete response to treatment. Neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper-respiratory infection, diarrhea, fever, cough, vomiting, and thrombocytopenia were among the most common adverse effects associated with treatment, according to the FDA.

At a meeting in July, an FDA advisory panel recommended the accelerated approval of both indications.

Brentuximab is under review for the same indications in Europe; a decision on approval is expected in the first half of 2012, according to a spokesperson for Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada.

The Food and Drug Administration on Aug. 19 approved brentuximab, a CD30-directed antibody drug-conjugate, for the treatment of Hodgkin’s lymphoma and systemic anaplastic large-cell lymphoma, after other treatments have failed.

Specifically, brentuximab was approved for the treatment of patients with Hodgkin’s lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It is the first new treatment approved for HL by the FDA since 1977, according to the FDA statement. The indications are based on response rates, and there are no available data that show "improvement in patient reported outcomes or survival" with treatment, according to the prescribing information.

The FDA also approved brentuximab for patients with systemic anaplastic large-cell lymphoma (ALCL), a rare form of lymphoma, after failure of at least one prior multiagent chemotherapy regimen. It is the first treatment approved for this rare lymphoma; approximately 2,000 new cases are diagnosed yearly in the United States.

Both types of lymphomas express the CD30 antigen. Brentuximab is a combination of an anti-CD30 antibody and a drug, monomethyl auristatin E (MMAE), a microtubule disrupting agent. The antibody directs the drug to C30-expressing tumor cells, where it is released.

Brentuximab is administered intravenously every 3 weeks; it will be marketed in the United States as Adcetris by Seattle Genetics. It will be available the week of Aug. 22, according to a company spokesperson.

The product was approved under the FDA’s accelerated approval program, which allows the agency to approve a drug for a serious disease based on data showing the drug is effective on a surrogate end point that is "reasonably likely" to predict clinical benefit. Accelerated approvals provide patients with access to promising treatments, but companies are required to provide confirmatory clinical data in order for the drug to be converted to a full approval and remain on the market.

"Early clinical data suggest that patients who received Adcetris for Hodgkin’s lymphoma and systemic anaplastic lymphoma experienced a significant response to the therapy," Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.

In a study of 102 patients with HL treated with brentuximab, 73% of the patients had either a complete or partial response to treatment. In a similarly designed study of 58 patients with ALCL, 86% achieved a partial or complete response to treatment. Neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper-respiratory infection, diarrhea, fever, cough, vomiting, and thrombocytopenia were among the most common adverse effects associated with treatment, according to the FDA.

At a meeting in July, an FDA advisory panel recommended the accelerated approval of both indications.

Brentuximab is under review for the same indications in Europe; a decision on approval is expected in the first half of 2012, according to a spokesperson for Millennium: the Takeda Oncology Co., which has rights to commercialize brentuximab outside the United States and Canada.