Onyx Unveils Results for Myeloma Drug, Raising Stakes in Rivalry with Millennium

12/7/10Follow @xconomy

Onyx Pharmaceuticals is betting that it can keep growing on the strength of a new cancer drug that’s supposed to compete with a blockbuster from Cambridge, MA-based Millennium: The Takeda Oncology Company. Today, Onyx is presenting key data to gird for the market battle.

Onyx, the Emeryville, CA-based biotech company (NASDAQ: ONXX), is reporting today on a clinical trial of 266 patients that shows its lead cancer drug in development, carfilzomib, shrank tumors by at least half in 24 percent of the sickest patients with multiple myeloma, a deadly cancer of the bone marrow. About one-third of these patients saw what was considered a clinical benefit, while two-thirds didn’t. The remissions lasted a median time of 8.3 months, and patients had a median overall survival time of 15.5 months.

These patients weren’t randomly assigned to another treatment option, so it’s impossible to say how much better this drug is compared to another round of currently available therapies. But previous studies suggest that patients this sick-whose disease had only worsened after a median of five rounds of therapy—had a life expectancy of about six to nine months, says David Siegel, a myeloma specialist at Hackensack University Medical Center in New Jersey, and an investigator on the study. He is presenting the data today at the American Society of Hematology meeting in Orlando, FL.

“The patients in this trial were rapidly approaching the end of their lives, and we saw some incredibly deep and durable responses in patients for whom we had no reason to expect that,” says Siegel. “Unabashedly, I love this drug and I can’t wait for it to be approved.”

About 20,000 patients are diagnosed in the U.S. with myeloma each year, and about 10,000 die from it, according to the American Cancer Society.

Onyx’s findings shouldn’t be much of a surprise to investors, since the company reported on the basic overall tumor shrinkage rate back in July. What’s new and meaningful today is how long the remissions lasted, the survival times, and the side effects.

Before going into the clinical details, first a little background. Like Millennium’s $1 billion blockbuster, bortezomib (Velcade), the Onyx drug is 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, you could fight cancer a novel way. The idea was to block the release of certain proteins that cancer cells secrete to grow and resist conventional chemotherapies.The Millennium drug has shown an impressive ability to shrink tumors of multiple myeloma patients, and its wide adoption, along with a different product from Celgene, lenalidomide (Revlimid), is widely credited among doctors with helping make myeloma more like a chronic disease than a near-term death sentence.

The catch, and there is always is one in the pharma business, is in the side effect profile. Most patients on the Millennium drug get peripheral neuropathy, a numbness and tingling in the fingers and toes that is a sign of nerve damage. Onyx, which obtained carfilzomib a year ago via the acquisition of South San Francisco-based Proteolix, is hoping to differentiate its product not just by helping patients who have run out of other options, but by offering a product with a more tolerable side effect profile.

Here’s what researchers are learning today about carfilzomib’s side effects. About 77 percent of patients had mild to moderate forms of peripheral neuropathy when they entered the study. New cases of this effect, or worsening of it was uncommon, researchers said. Less than 1 percent of patients reported a case of moderate to severe peripheral neuropathy on the Onyx drug. That’s good by cancer drug standards, but like many other anti-cancer compounds, this product is known to also knock out many types of blood cells. The most common moderate to severe side effects were thrombocytopenia, a depletion of clot-forming platelet cells (27 percent); anemia, a reduction in oxygen-carrying red blood cells (22 percent); and neutropenia, a lowering of infection-fighting white blood cells (10 percent).

Onyx has said it plans to seek FDA approval on the basis of this set of data by mid-2011, after it resolves some manufacturing issues that have held up its application by an estimated six months.

Millennium, of course, isn’t ready to back down. The company released some data yesterday at ASH from a study called MMY-3021, which suggested it was able to reduce the cases of peripheral neuropathy by developing a new formulation of bortezomib that can be injected just under the skin—a more convenient delivery route than the traditional intravenous infusion. Millennium said that 38 percent of patients experienced peripheral neuropathy after getting the subcutaneous bortezomib, compared with 53 percent who reported that effect with the intravenous form. Millennium, as I described in a feature story last week, is also seeking to figure out the best dosing schedule for maintenance therapy after patients have already had their tumors knocked down successfully in an early round of treatment.

Onyx is seeking over time to gain traction among myeloma patients with earlier stages of disease, but if it can win FDA approval, its initial market will be in a niche with patients who have essentially run out of other options. Even though myeloma is a relatively rare disease, it represents a big business opportunity. The worldwide market for myeloma drugs is worth an estimated $4 to $5 billion a year, Onyx has said. The Onyx drug could capture about $275 million in worldwide sales in 2014, according to forecast from analyst Christopher Raymond with Robert W. Baird, in a note to clients Nov. 4.

Despite Siegel’s enthusiasm, this drug doesn’t work for everybody. About one-third of patients had at least a minimal response that was classified as a clinical benefit, but that still means that about two-thirds of patients didn’t respond to therapy. Onyx doesn’t really know why some patients responded while others didn’t, Kauffman says.

For those lucky enough to respond to carfilzomib therapy, the news is much better, partly because of its tolerability. “What’s exciting about carfilzomib, we have been able to give it for two years without significant side effects accumulating,” Kauffman says. About 12 percent of patients dropped out of the study because of side effects, he says.

Siegel, the investigator who’s presenting the carfilzomib results, said he expects doctors to continue prescribing the hit Celgene product lenalidomide (Revlimid) and Millennium’s bortezomib as they are used today. The Onyx drug will initially be used in patients who stop responding to the others. But he raves about the side effects and tolerability of the new product. Onyx, and many investigators, clearly see potential in moving the new drug ahead with patients at earlier stages of treatment.

“It works well, and when it does work, it’s not a 15-minute kind of thing,” Siegel says. “It’s exceptionally well-tolerated. It’s a triple.” Some of his peers may question how sick some of the patients in this study really were, and how many were truly resistant to other therapy, or refractory. The criticisms, Siegel predicts, won’t stand up over time.

Onyx executives plan to discuss the findings in detail today on a webcast with investors at 10 am Eastern/7 am Pacific time.

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