National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 26, 2011 • Volume 8 / Number 15

FDA Update

Advisory Panel Recommends Accelerated Approval for Brentuximab

A Food and Drug Administration (FDA) advisory committee has unanimously voted in favor of granting accelerated approval of the drug brentuximab vedotin (Adcetris) for some patients with Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). The FDA must decide by August 30 whether to grant accelerated approval for brentuximab for these two indications. The agency is not bound by the committee's recommendations.

The FDA's accelerated approval process makes available potentially beneficial therapeutic options for serious diseases with an unmet medical need. Larger confirmatory trials are then required to validate the findings from the earlier trials and transition the drug to a regular approval.

The votes from the FDA's Oncologic Drugs Advisory Committee were based on the results of two single-arm phase II trials that tested brentuximab in patients with Hodgkin lymphoma who had relapsed after an autologous stem cell transplant and in patients with relapsed or refractory ALCL, respectively. In both cases, there are few proven treatments for these patients. Results from the trials were presented in December at the American Society of Hematology annual meeting.

Brentuximab is an antibody-drug conjugate, an antibody that is chemically linked to a drug. The antibody component of brentuximab targets the CD30 protein, which is expressed on the surface of most Hodgkin lymphoma and ALCL cells but very few noncancer cells; the linked drug is the chemotherapy agent MMAE.

In the 102-patient Hodgkin lymphoma trial, three-quarters of patients had substantial tumor shrinkage (objective response) and one-third of patients had their tumors eradicated (complete response). In the 58-patient ALCL trial, 86 percent of patients had an objective response and just over half had a complete response.

Seattle Genetics, which developed brentuximab, had sought a regular approval for the drug. But because "a clear understanding of a risk-to-benefit evaluation may not be optimal from single-arm trials," the FDA recommended that the drug move forward initially under the accelerated approval process, explained Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research.

Despite the unanimous vote in favor of accelerated approval, the FDA and several committee members said that a phase III clinical trial being conducted in patients with Hodgkin lymphoma, called ATHERA, was not properly designed to be an adequate confirmatory trial and that at least one other trial would be necessary to eventually gain regular approval.

"There is no question that this drug works," said ODAC Chair Dr. Wyndham Wilson of NCI's Center for Cancer Research. But, among other concerns, he added that because of the way the ATHERA trial was designed it will probably not identify those who are most likely to benefit from the drug, including those who might be cured by its use.

The FDA and Seattle Genetics, which developed and manufactures brentuximab, will further discuss the appropriate design of confirmatory trials to support regular approval of brentuximab for Hodgkin lymphoma and ALCL, according to an FDA spokesperson.

"We are committed to working with the FDA on the ATHERA trial and other clinical trials as part of a confirmatory study package to support regular approval," said Seattle Genetics CEO Dr. Clay Siegall during a conference call with investment analysts.

Carmen Phillips