A Phase III failure of Nexavar in advanced melanoma thumped Onyx Pharmaceuticals Inc.'s stock by more than 30 percent Monday.
Shares of the Emeryville, Calif.-based company (NASDAQ:ONXX) fell $5.32, ending the day at $12.18.
Nexavar (sorafenib), which won FDA approval in kidney cancer last December, did not improve progression-free survival when compared with placebo in melanoma patients. Each arm included treatment with carboplatin and paclitaxel.
While specific data were not disclosed, the company said the treatment effect was comparable in each arm.
"Our enthusiasm for Nexavar is not diminished," said Julie Wood, Onyx's vice president of investor relations and corporate communications. "This was a single trial outcome in a specific disease setting, and we continue to have a very broad clinical development program across tumor types and in multiple disease settings."
The international melanoma trial was double-blind, randomized and placebo-controlled, and involved 270 patients that were progressing in disease after one previous treatment with either dacarbazine or temozolomide.
They were treated on a standard dosing schedule - a 21-day cycle - with carboplatin and paclitaxel. Progression-free survival was the primary endpoint. The safety profile of Nexavar in combination with the chemotherapeutic agents was comparable to what was previously seen.
Hollings Renton, chairman, president and CEO of Onyx, said in a conference call that the progression-free survival results "don't change our outlook or our confidence" in Nexavar, which is in Phase III trials for advanced liver cancer and non-small-cell lung cancer. The liver cancer trial has completed enrollment, and results should be available "toward the end of 2007," said Hank Fuchs, the company's executive vice president and chief medical officer.
The NSCLC trial began earlier this year. (See BioWorld Today, Feb. 17, 2006.)
Onyx officials declined to give detailed data on the melanoma trial, or to say whether the result was due to the chemotherapy arm doing better than expected or the Nexavar arm doing worse. They plan to disclose all data at a scientific meeting next year, possibly at the American Society of Clinical Oncology gathering.
Further development of Nexavar will be concentrated on "more common malignancies in which anti-angiogenics have demonstrated activity," Renton said. A breast cancer program is expected to start in the coming year.
"Many successful drugs have had failures in clinical trials," Fuchs said, citing South San Francisco-based Genentech Inc.'s cancer drug Avastin.
Melanoma accounts for 4 percent of skin cancer cases, but is responsible for 77 percent of the deaths. In the U.S., there will be about 62,000 new cases for 2006. Worldwide, about 132,000 are diagnosed each year.
An oral multi-kinase inhibitor, Nexavar targets both the tumor cell and tumor vasculature. It addresses members of two classes of kinases related to cell proliferation and angiogenesis, including RAF kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT and FLT-3. It is partnered with Bayer Pharmaceuticals Corp., of West Haven, Conn.
In addition to the U.S., Nexavar is marketed in the European Union for advanced kidney cancer. Third-quarter U.S. and European sales were $45 million, with about 10 percent attributed to off-label use in a variety of tumor types, including melanoma.
Nexavar also is the subject of several outside trials sponsored by government agencies, cooperative groups and individuals.