Seattle Genetics’ FDA Panel Preview: What You Need to Know This Week

7/12/11Follow @xconomy

[Updated: 6:50 am PT] This is the week Seattle Genetics, a 14-year-old company, will have its biggest coming-of-age experience on its way to becoming a real grown-up.

The company (NASDAQ: SGEN) is getting ready to make its best possible argument for FDA approval of its new “empowered antibody” drug aimed at a pair of rare lymphomas. The evidence so far for this treatment, brentuximab vedotin (Adcentris), was posted in staff briefing documents on the FDA website, in advance of an FDA advisory committee meeting of cancer drug experts on Thursday in Silver Spring, MD.

The FDA panel’s review represents a huge moment for Seattle Genetics, and also could send a ripple effect through the biotech industry, and the Northwest’s local biotech cluster. If Seattle Genetics can persuade the expert panel to recommend its drug, and the FDA formally approves the treatment by its Aug. 30 deadline, then it will be the company’s first marketable product after spending 14 years and more than $500 million. It will also clear the way for what could be the first commercial success with a “smart bomb” antibody that zeroes in on tumors, while unleashing a potent toxin that hits the cancer and mostly spares healthy tissues.

For Seattle’s biotech community, it would mark the second time in two years that a local company has been able to blaze a trail with a new class of cancer drug, following last year’s FDA approval of an immune-boosting cancer fighter from Dendreon (NASDAQ: DNDN). And while about two-thirds of the 8,500 patients diagnosed in the U.S. with Hodgkin’s disease are successfully treated with chemotherapy, one-third eventually get relapsed, treatment-resistant forms that provide a grim prognosis-a life expectancy of just two to three years. If Seattle Genetics can win approval, it will start selling the first new drug for Hodgkin’s since 1977.

Eric Dobmeier

“We think this is very important for the industry and for cancer patients,” says Eric Dobmeier, Seattle Genetics’ chief operating officer. The combination of antibodies fused to potent toxins, sometimes called antibody-drug-conjugates, “have the potential to impact the way many cancers are treated. They are more targeted, and less toxic than chemotherapy,” Dobmeier says.

The evidence from clinical trials that Seattle Genetics has put together is “spectacularly positive,” says David Miller, president of Biotech Stock Research, an independent research firm. Seattle Genetics has been careful not to get overly confident in its public statements, but Dobmeier did say in an interview last week, “we believe we are on strong ground.” The debate, Miller says, is most likely to hinge on which specific patient populations ought to be included in the prescribing information.

The FDA and its expert panel are looking at data from more than 300 patients in clinical trials, and especially at two late-stage studies for Hodgkin’s lymphoma and anaplastic large cell lymphoma. Details from these studies were presented in December at the American Society of Hematology meeting in Orlando, FL.

To recap: Seattle Genetics conducted a pivotal study of its drug in 102 patients with relapsed forms of Hodgkin’s disease who had essentially run out of other options. Researchers found that one-third of the patients (34 percent) had their tumors completely wiped out after getting the new Seattle Genetics drug, while another 41 percent had their tumors shrink by half or more, meaning there was a tumor response rate of 75 percent. The tumor shrinkage lasted a median time of about six months when researchers looked at all patients, and about 20 months for the subset who had complete responses, Seattle Genetics has said. The company can’t yet calculate the median survival time for patients in this trial, which began in February 2009, because 89 percent of the patients are still alive, Dobmeier says.

The prognosis is so bad for patients in this group that a 30 percent tumor response rate probably would have been good enough to seek FDA approval, Seattle Genetics CEO Clay Siegall has said.

Side effects in this trial were typical of what you see in cancer studies. Almost half (47 percent) of patients experienced some degree of peripheral neuropathy, which is nerve damage/tingling in the fingers and toes. Another 46 percent reported fatigue, 42 percent reported nausea, and 37 percent had upper respiratory tract infections during the study. Among the moderate to severe side effects, researchers reported that one-fifth had a depletion of their infection-fighting white blood cells, known as neutropenia. About 8 percent of the cases of peripheral neuropathy were considered moderate to severe. Another 8 percent of patients had significant depletion of clot-forming platelet cells in the blood (thrombocytopenia), and about 6 percent reported a significant reduction in their oxygen-carrying red blood cells (anemia).

This trial, in Hodgkin’s patients, didn’t randomly assign patients to a control group, which is usually a standard part of the trial design the FDA wants in order to be confident that a drug is really working. In this case, Seattle Genetics sought to work around that requirement because relapsed Hodgkin’s is a small patient population, and it probably would have been difficult and much more time-consuming to enroll patients in a trial if they knew they had a 50-50 chance of getting a placebo or other drug unlikely to work. FDA advisors have made comments in the past, Dobmeier says, that randomized trials should be required for cancer drugs, except in cases of rare diseases, and when a drug’s tumor-shrinkage rate is very high.

“Because Hodgkin’s is rare, and we have such strong data, we believe we are on strong ground,” Dobmeier says.

The other important trial, which the FDA panel will consider in an afternoon session on Thursday, looks at the drug’s effect in patients with another malignancy that carries the same CD30 biological target found on Hodgkin’s cells that brentuximab is designed to hit. This trial, of patients with anaplastic large cell lymphoma, was a small one of just 58 patients. But the response rate was even more profound here. Researchers said 50 of the 58 patients (86 percent) had significant tumor shrinkage, and more than half had their tumors eradicated. The company is still following up with patients to see how long those tumor remissions are lasting, and how long the patients are living.

Seattle Genetics has bundled these two trials together in its application, and is seeking clearance to market the product to doctors who treat both patient populations. The company also is working to expand use of the drug across broader patient populations than the ones tested in clinical trials, which will likely be a topic of conversation at the FDA panel. In the Hodgkin’s study, for instance, it only enrolled patients whose disease had worsened after chemo, and after an autologous stem cell transplant. But Seattle Genetics is seeking language in the drug’s prescribing information to suggest patients could benefit from the drug even if they haven’t yet failed to respond to a stem cell transplant, because data from other small trials suggests they, too, can benefit from the new treatment.

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