An FDA panel of oncologists has voted against a new use for Amgen's Xgeva in prostate cancer on Wednesday, saying the drug's ability to slow the spread of the disease did not translate into meaningful benefits for patients. Xgeva is already approved to prevent fractures in cancerous bones, and for osteoporosis, in a different formulation called Prolia.
The Food and Drug Administration's cancer drug panel voted 12-1 that the benefits of the drug did not outweigh its risks, which included bone disease in about 6 percent of patients. The FDA is not required to follow the group's advice, though it often does. At the public meeting Wednesday, Amgen scientists pointed to results of a company study showing patients taking Xgeva experienced a four-month delay in the spread of cancer to the bones around the prostate.
A 1,432-patient study conducted by Amgen showed the drug slowed the spread of cancer to the bone by about 4.2 months when compared to patients who received placebo. While that delay was statistically significant, the FDA's reviewers questioned whether it is “an adequate measure of clinical benefit” for patients with prostate cancer. Panelists termed this a “statistical benefit,” but not one that resulted in increased survival or higher quality of life for patients. “The effect of the studied compound is quite weak with no effect on survival or the overall course of the disease in general,” said Dr. Ronald Richardson of the Mayo Clinic. All of the panel's physicians voted against the company's application. The lone patient representative on the panel voted in favor.
Many cancer drugs approved by the FDA do not actually extend survival, but instead slow the growth of tumors or their spread to other parts of the body. In recent years, cancer experts have debated the meaningfulness of these measures. Panel chair Dr. Wyndham Wilson acknowledged that delaying the disease's spread to the bone could be meaningful, but suggested the drug would have to do so for more than four months. “If it was one year we probably wouldn't even be here today, no one is denying that that, but the magnitude here is quite low” said Wilson, a research chief at the National Cancer Institute.
Panelists also raised concerns about exposing patients to the drug's side effects, including osteonecrosis of the jaw, in which the bone dies because of poor blood supply. While the FDA staff does not openly recommend against the new use for the drug, they do quote from an editorial in the Lancet which said the company's findings on Xgeva “do not support its broad use as a preventive agent for bone metastases in prostate cancer.”
All of the men in Amgen's study had tumors that did not respond well to hormone therapy, but had not yet spread beyond the prostate. While there are multiple drugs for both early and late-stage prostate cancer, Amgen argued “there is a gap in the treatment plan for those patients” enrolled in its study. Amgen said in a statement following the meeting that it would continue discussions with the FDA as it reviews the company's application. A final decision is expected by April 26.
Xgeva and Prolia, the osteoporosis formulation, had combined sales of $554 million in 2011, their first full year on the market. ISI analyst Mark Schoenebaum said the FDA's negative review was consistent with analyst expectations. “As was generally expected by us and much of the Street, the FDA is critical of the data, questioning the clinical meaningfulness of the primary endpoint,” Schoenebaum wrote in an email. Even if the FDA ultimately approves the indication, Schoenebaum estimates modest U.S.sales of about $300 million. The FDA is expected to make its final decision by late April. Shares of Thousand Oaks, Calif.-based Amgen fell $1.80, or 2.6 percent, to $67.48 per share in morning trading.
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