Onyx Preps for Dash to FDA, After Myeloma Drug Helps Sickest of the Sick

7/26/10Follow @xconomy

Tony Coles has been pushing for two years to re-fashion Onyx Pharmaceuticals into more than a one-drug company, and now he might have the data to make that happen.

The Emeryville, CA-based biotech company (NASDAQ: ONXX) is announcing today that its drug candidate for multiple myeloma was able to at least partially shrink tumors for about one-fourth of patients who were so sick they had essentially run out of other options. Those fortunate enough to respond to therapy stayed in remission a median time of 7.4 months. Side effects—such as pneumonia, anemia, and depletion of infection-fighting white blood cells—were consistent with findings from a previous study. The evidence from the latest trial of 266 patients was strong enough that Onyx plans to use the data to seek FDA approval for its drug, carfilzomib, before the end of this year.

Onyx has been built on the back of one hit drug for kidney and liver cancer, sorafenib (Nexavar), which generated $843 million in sales last year for Onyx and its partner, Germany-based Bayer. Onyx has been seeking to diversify its portfolio for years, and made an aggressive move last October when it agreed to acquire South San Francisco-based Proteolix for as much as $535 million to obtain whole ownership of carfilzomib. About 20,000 people get diagnosed with multiple myeloma, a cancer of the bone marrow, each year in the U.S., and about 10,000 people die from the disease annually, according to the American Cancer Society.

Multiple myeloma therapy is dominated today by Cambridge, MA-based Millennium: The Takeda Oncology Company and Summit, NJ-based Celgene. Onyx is hoping this new set of results in the sickest patients will help it capture some significant share of a worldwide market that’s worth an estimated $4 to $5 billion a year, and still growing.

“This data really validates our growth strategy, and the acquisition of Proteolix,” Coles says.

Tony Coles

Tony Coles

Only a portion of the data is being made public to investors today, and much more detailed information will have to come later at a medical meeting or in a peer-reviewed journal. So there is plenty of room for skeptics to question the results being announced today, or at least reserve judgment for a later time.

That said, here’s the gist of what Onyx is reporting. This trial enrolled 266 patients who had previously relapsed and stopped responding to a median of five prior courses of therapy that usually included Millennium’s bortezomib (Velcade), Celgene’s lenalidomide (Revlimid), and dexamethasone, a common anti-inflammatory drug. Based on historical records, patients this sick were expected to respond to therapy about 11 percent of the time, and have a life expectancy of about six to 10 months.

These patients’ last hope was essentially to enroll in the Onyx study, in which they got regular intravenous infusions with carfilzomib. The Onyx drug, like Millennium’s treatment, is what’s known as a proteasome inhibitor. Millennium blazed this trail almost a decade ago, showing that if you can make a drug to inhibit these enzymes that act as a cellular garbage disposal, then you might block the release of certain proteins that cancer cells secrete to grow and resist conventional chemotherapies.

Because the patients who enrolled in this study were extremely sick, and had already cycled through all the other therapies, the trial was designed to simply enroll patients on the Onyx drug without randomly assigning them to a placebo or any other drug that could offer a comparison.

Heading into this study, Onyx said it was hoping to see at least partial tumor shrinkage in a “high-teens” percentage of patients, and a duration of remission of at least four to six months, Coles says. While those measurements are important to the FDA and physicians, the study also looked at other key goals such as how long the drug could keep tumors from spreading (what’s known as progression-free survival) and the gold standard of cancer drug development—overall survival time. Data on progression-free survival and overall survival times isn’t being released today, and will have to come out at a future medical meeting, Coles says.

Even with just a few leading indicators being released today, an important patient advocacy group cheered the result.

“These are noteworthy results in this refractory population,” says Susan Kelley, chief medical officer of the Norwalk, CT-based Multiple Myeloma Research Consortium. The consortium helped enroll more than half the patients in the study.

Even though Onyx doesn’t yet have data from the third and final phase of clinical trials usually required for FDA approval, Coles says it has good reason to take its existing database to U.S. drug regulators for a review later this year. That’s because the FDA has published guidelines that say it will consider reviewing non-randomized studies for certain blood cancers, as long as the treatment is for a patient population that truly doesn’t have other options, and the drug appears to have a good balance of safety and effectiveness, Coles says.

The FDA has lived up to its word recently, granting approval to a couple of other companies in a similar situation, Coles says. Westminster, CO-based Allos Therapeutics (NASDAQ: ALTH) and Cambridge, MA-based Gloucester Pharmaceuticals both won clearance from the FDA to start selling drugs for blood cancers that hadn’t gone through traditional randomized studies, he says.

Still, Onyx needs to run a bigger study to fulfill the sales potential of its treatment for multiple myeloma. The company is currently enrolling patients in a 700-patient trial, called Aspire, which will randomly assign patients to a combination of Celgene’s lenalidomide (Revlimid), low-dose dexamethasone, and Onyx’s carfilzomib, or just the first two drugs alone. This study is designed to enroll patients with an earlier stage of disease who have a better prognosis and therefore ought to have better odds of responding to treatment. A posting on clinicaltrials.gov says that Onyx expects to have data on the primary goal of the study by October 2011, although Coles says he hasn’t provided a timeline for when investors should expect results.

If Onyx can persuade the FDA that this first trial is good enough to earn a place on the market for the sickest of the sick, and the next trial provides compelling proof that the drug is useful at an earlier stage of disease, then this could be a big story for years to come for Onyx. Getting clearance in both patient populations could be enough for carfilzomib to generate $1 billion in peak annual worldwide sales, Coles says.

While it may not be a cure, the results do represent an additional piece of good news for patients with multiple myeloma, who have benefitted immensely from innovative new treatments of the past decade, according to Kelley of the Multiple Myeloma Research Consortium. Millennium and Celgene have set the bar much higher than ever before for multiple myeloma, so Onyx clearly has had its work cut out.

“It’s incredible how much this field has evolved. We hope to see it [multiple myeloma] become more like a chronic disease,” Kelley says.

Onyx plans to discuss the data and business implications on a conference call with analysts this morning at 8 am Eastern/5 am Pacific. To listen to a live webcast, click here.

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