FDA Staff Questions Benefits of Glaxo, Merck Cancer Drugs

GlaxoSmithKline Plc. (GSK) and Merck & Co. (MRK) and Ariad Pharmaceuticals Inc. (ARIA)’s drugs for a rare, often deadly form of cancer may not offer enough benefits to be worth risks including heart and kidney ailments, U.S. regulators said.

While Votrient from London-based Glaxo kept sarcoma from spreading in soft tissue, it didn’t prolong patients’ lives, Food and Drug Administration staff wrote in a report today. Ridaforolimus, developed by Merck and Ariad, didn’t keep patients alive longer or stop progression of the disease, according to an FDA report.

Votrient and the Merck-Ariad drug, which might be called Taltorvic if approved, would be the first targeted treatments for a cancer that invades soft tissue such as muscle, tendons and fat outside the stomach and intestines. Chemotherapy is now used for these tumors.

“If patients come to the oncologist with cancer, they want to be cured,” said Gary Schwartz, chief of melanoma and sarcoma service at the Memorial Sloan-Kettering Cancer Center in New York, in a telephone interview. “But with sarcoma, they aren’t cured, they want to live longer.”

The median survival of patients diagnosed with soft-tissue sarcoma that is spreading is about a year, according to the FDA documents.

Advisers to FDA are scheduled to meet March 20 to review the drugs. The agency is set to decide on Glaxo’s drug by May 6 and Merck’s medicine by June 5.

Ariad fell less than 1 percent to $15.41 at the close of New York trading. Merck declined less than 1 percent to $38.03. Glaxo also dropped less than 1 percent to 1,423.5 pence in London.

Sarcoma Varieties

About 10,000 cases of soft-tissue sarcoma are diagnosed each year, Richard Riedel, an oncologist and assistant professor at the Duke University School of Medicine in Durham, North Carolina, said in a telephone interview.

There are about 50 types of soft-tissue sarcoma, which are different from carcinomas that arise from cells, according to the American Cancer Society. Most sarcomas are in the arms and legs or internal organs, according to the National Cancer Institute.

Sarcoma tumors also can develop in bone tissue. About 2,500 new cases are diagnosed a year, according to the University of California, San Francisco. Ridaforolimus, the experimental drug from Whitehouse Station, New Jersey-based Merck and Cambridge, Massachusetts-based Ariad, also would treat bone sarcoma.

Chemotherapy is effective at shrinking the tumor in 20 percent to 25 percent of patients, said Scott Okuno, an oncologist at the Mayo Clinic in Rochester, Minnesota. Once tumors have spread, a minority of patients are cured, he said in a telephone interview.

‘Most Effective Drugs’

“These are the most-effective drugs we have,” Okuno said. “The sarcoma community is always looking for newer agents that have efficacy.”

In rare cases, tumors develop in the stomach and small intestine. Two existing drugs are approved for these gastrointestinal sarcomas: Pfizer Inc. (PFE)’s Sutent and Novartis AG (NOVN)’s Gleevec.

While Glaxo’s Votrient increased progression-free survival, it didn’t have a significant effect on overall survival, according to FDA staff. The difference between Merck and Ariad’s drug and placebo at increasing progression-free survival is small, the FDA said. The agency asked the panel to weigh whether either drug’s benefits outweigh the risks.

Longer Than Placebo

Glaxo’s Votrient, chemically known as pazopanib, enabled patients to live a median 4.6 months, or 3.1 months longer than placebo, while the disease stopped advancing, according to a statement from the London-based company. The final-phase trial studied 369 patients with certain metastatic soft tissue sarcomas that didn’t respond to chemotherapy.

The trial excluded patients with gastrointestinal tumors. The FDA approved Votrient in 2009 to treat advanced renal cell carcinoma.

There’s “quite a bit of excitement” about expanding approval for Votrient, said Riedel, who has done consulting work for Merck. It’s an oral medication that blocks proteins that send growth signals to cancer cells, he said.

Ridaforolimus Effect

Patients stayed alive and free of disease progression on Merck and Ariad’s ridaforolimus for a median 17.7 weeks, or 3.1 weeks longer than placebo, according to a statement from the company. The final-phase trial tested 711 patients, 347 on the compound, with soft-tissue sarcoma that spread to other areas of the body or bone sarcomas that previously responded favorably to chemotherapy.

Merck interprets the data differently. Ridaforolimus prolonged life without disease progression 6 weeks longer than placebo, Eric Rubin, vice president and therapeutic area head of oncology clinical trial development at Merck, plans to tell the advisory panel.

“We do think that’s clinically meaningful,” he said.

Since patients can’t stay on chemotherapy indefinitely because of harsh side effects, ridaforolimus would be used to delay progression of the disease after the treatment, Rubin said in a telephone interview. The medication inhibits a pathway activated in sarcoma, he said.

Merck is responsible for the development and worldwide commercialization of ridaforolimus in oncology, while Ariad has co-promotion rights in the U.S., Pamela Eisele, a Merck spokeswoman, said in an e-mail.

To contact the reporter on this story: Anna Edney in Washington at aedney@bloomberg.net

To contact the editor responsible for this story: Adriel Bettelheim at abettelheim@bloomberg.net

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