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

7/12/11Follow @xconomy

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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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