Onyx Drug Effective in New Myeloma Patients, Taking Aim at Millennium

12/12/11Follow @xconomy

[Updated: 8:45 am PT] Onyx Pharmaceuticals has set its sights on shaking up the standard of care for a deadly cancer of the bone marrow, and now results from at least one small study suggest it has a shot.

Researchers are reporting today that when the experimental treatment from South San Francisco-based Onyx (NASDAQ: ONXX) was combined into a three-drug regimen, it increased the odds that multiple myeloma patients would see a significant shrinkage of their tumors, without the nerve damage in fingers and toes that limits dosing of the existing standard of care. The study looked at 53 patients getting their first round of therapy for multiple myeloma with a combination of Onyx’s carfilzomib, Celgene’s lenalidomide (Revlimid), and low-dose dexamethasone.

Many details of the trial were released last month on the American Society of Hematology’s website, and they will be formally discussed further at 5:45 pm Eastern/2:45 pm Pacific time today in an oral presentation at the organization’s annual meeting in San Diego.

“We now have a regimen which is well-tolerated, efficacious, and can be used for an extended period of time with limited need for dose [adjustments],” says Andrzej Jakubowiak, the director of the multiple myeloma program at the University of Chicago Medical Center, and the study’s lead investigator. “The results were beyond my expectations.”

The new batch of results is still preliminary, and there was no control group, so it’s impossible to say how well the Onyx drug is performing compared to other treatments. Still, it could have big implications for Onyx’s business and that of its primary competitor—Cambridge, MA-based Millennium: The Takeda Oncology Company. Onyx is seeking FDA approval of carfilzomib, at least initially, as a treatment for the very sickest of patients who have relapsed and developed resistance against other treatments. But because the Onyx drug—a proteasome inhibitor like Millennium’s—has shown strong effectiveness combined with a milder effect on peripheral nerves, researchers have long been curious about its potential to go beyond the sickest patients, and offer a new option for the larger group of newly diagnosed patients.

Still, shares dipped 5 percent to $38.33 at 11:41 am Eastern today, after Onyx said the FDA has declined to provide  a faster-than-usual six-month review of the new drug, which the agency sometimes grants to groundbreaking therapies. The FDA’s deadline to complete its review of the Onyx application is set for July 27th.

About 20,000 people are diagnosed with myeloma each year in the U.S., and 10,000 die from it annually, according to the American Cancer Society. Millennium: Takeda’s drug bortezomib (Velcade) became a billion-dollar annual blockbuster by advancing the standard of care in these patients, so if Onyx can deliver comparable or better clinical results, it has an opportunity to tap a very big market.

“While development in this setting [front-line therapy] is still in early stages, we think it looks promising and is a major driver of investor optimism for the long term future of carfilzomib,” said Cory Kasimov, an analyst with JP Morgan, in a note to clients Dec. 4.

Here’s what the researchers found: When patients went on the three-drug combo that included the new Onyx treatment, 46 of 49 people (94 percent) had their tumors shrink at least by half within the first month. That number climbed to 100 percent after four months, and stayed at 100 percent through 12 months of follow-up. More than half (53 percent) of patients went into complete remission after the first month of therapy, and that figure kept rising to 79 percent after 12 months of follow-up, researchers said. All 19 patients who were followed through their 12 cycles of treatment have achieved what’s known as a “very good partial response,” in which their tumors have shrunk by at least 90 percent.

Side effects were predictable, and mostly mild, by cancer drug standards. About 18 percent of patients had moderate to severe anemia, another 12 percent had moderate to severe depletion of their infection-fighting white blood cells, and 10 percent had a significant drop in platelet cells that help the blood form clots. Six patients dropped out of the study, although only one quit because of toxicity, researchers said. About 24 percent of patients experienced tingling and numbness in fingers and toes (peripheral neuropathy), but those cases were rated only mild to moderate in intensity.

When doctors today use Millennium’s Velcade, patients often complain of nerve tingling and numbness, which prompts doctors to adjust the dosage, or the scheduling of doses, Jakubowiak says. Those tweaks have helped patients, but Jakubowiak says his preference is to keep the dosages high and consistent as long as they are tolerated, to give the patient the best chance at a complete and long-lasting remission.

“The dose manipulations have created some improvements, but nevertheless, it is the big limitation of the Velcade regimen,” Jakubowiak says.

Onyx is evaluating its options for how to build on this small study, by looking at carfilzomib as part of the three-drug combo strategy in a pivotal stage study for newly diagnosed patients, says company spokeswoman Lori Melancon. The company is also in the midst of conducting a pivotal clinical trial of the carfilzomib regimen in relapsed patients.

Jakubowiak says he’s eager to see what scientists can learn from the upcoming trials.

“In my opinion, it’s rare that such a good regimen comes along. The improvement is not a dramatic change, but it’s strong enough that the results are unquestionably better than what we’ve seen before,” Jakubowiak says. “I’d like to build on it.”

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