Blood cancer drug trial results questioned by FDA

By Dr. Ananya Mandal, MDJul 13 2011

U.S. drug reviewers might limit the use of a Seattle Genetics Inc’s experimental blood cancer drug due to the narrow scope of its clinical trials. According to papers released Tuesday by the Food and Drug Administration (FDA), it requests an advisory panel to consider the drug, under the proposed trade name Adcetris known chemically as brentuximab vedotin, for use in previously treated patients with Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL).

About 9,000 Americans a year are diagnosed with Hodgkin's lymphoma and 3,000 with ALCL.

“Small size limits the benefit-risk analysis,” the FDA said in questions to outside advisers released with its report. “For this application, consideration for accelerated approval would be consistent with regulatory actions taken in the past decade for similar hematology applications based on single arm clinical trials.” The reviewers at the FDA suggested the labeling for Hodgkin's should focus on a smaller patient group than expected, limiting potential sales. FDA says, the drug should be considered for patients who had already been given a stem cell transplant, rather than on all treated patients as suggested by the company. The FDA advisory panel votes on the drug on Thursday.

Seattle Genetics shares closed 74 cents down at $19.80 on the Nasdaq. They hit an all-time high of $21.41 on June 28 after European health regulators accepted an application to market the drug for both Hodgkin's and ALCL in Europe.

In preliminary trials, Adcetris, given in a 30-minute infusion every three weeks, demonstrated complete response rates and reduced tumor size in more than 90 percent of patients - 94 percent for Hodgkin's and 97 percent for ALCL, the company said. The major side effects for both included nerve damage, infections, reactions from the infusion and myelosuppression, a common side effect from chemotherapy that causes decreased blood cell production. One patient also dropped out of the Hodgkin's study because of Stevens Johnson Syndrome, a life-threatening skin condition.

However, the mid-stage trials only included 58 patients for ALCL and 102 patients for Hodgkin's, and did not compare Adcetris to another drug. The FDA said these factors “limit the benefit-risk analysis.” The FDA reviewers also noted that no second trial confirmed the clinical benefit of Adcetris in patients with ALCL, as required under priority review, and asked the advisory panel to weigh whether the drug should be given an accelerated approval without such confirmation.

Seattle Genetics Chief Executive Clay Siegall said in May that annual U.S. sales of Adcetris for Hodgkin's and ALCL would likely amount to less than $1 billion. But if the drug wins approval as a front-line therapy, or first treatment option, the annual U.S. sales could be “considerably over a billion dollars,” Siegall said. He added that he had a “high level of confidence” Adcetris would win U.S. approval by August 30 -- the early decision date set by the FDA.

Brentuximab vedotin links a tumor-targeting antibody to a cancer-killing chemotherapy drug with the goal of limiting side effects. It is designed to home in on an antigen, or foreign substance, in Hodgkin's lymphoma, several types of T-cell lymphoma and other hematologic malignancies.