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Seattle Genetics Sees Case of PML, Causing Market Twitch

Xconomy Seattle — 

Seattle Genetics has had a bit of a dust-up today in the stock market, as investors have been seeking to make sense of a second case of a dangerous adverse event seen in a patient on the company’s new lymphoma drug.

Shares of the company (NASDAQ: SGEN) dipped almost 6 percent early in the day, after Wall Street analyst Elliot Favus circulated a report about how a second case of progressive multifocal leukoencephalopathy (PML) has been diagnosed in a patient taking the company’s flagship lymphoma drug. Favus, known for his bearish positions, didn’t immediately respond to a request for a copy of his report.

Seattle Genetics stock regained much of its value as the day went on, but news on PML is bound to rattle nerves on Wall Street. That’s because this condition is a rare, and sometimes deadly, brain infection that patients sometimes get when taking modern targeted biologic drugs like Biogen Idec’s natalizumab (Tysabri), and Roche/Genentech’s rituximab (Rituxan). The Tysabri case in particular made headlines, and prompted that drug to be temporarily withdrawn from the market, until scientists better understood the risks and benefits. Since Seattle Genetics’ brentuximab vedotin (Adcetris) only arrived on the market in August, and Seattle Genetics depends heavily on it as its only marketed product, it’s understandable why investors got jumpy.

The Seattle Genetics drug, for patients with Hodgkin’s lymphoma and anaplastic large cell lymphoma, has shown impressive effectiveness in clinical trials. It provided significant tumor shrinkage in 75 percent of patients with relapsed forms of Hodgkin’s disease in a clinical trial, and in about 86 percent of patients with anaplastic large-cell lymphoma. Researchers are still following patients to see how long those responses really do last, and to what extent they may help people live longer. The most common side effects found in clinical trials were a depletion in infection-fighting white blood cells, nerve damage in the fingers and toes, fatigue, nausea, and anemia.

Clay Siegall

CEO Clay Siegall offered a spirited defense of his product today when I reached him by phone. The PML association with Adcetris isn’t new, he said, as the first page of the product’s FDA approved prescribing information includes a warning about the condition. The warning says that a patient in clinical trials, who had received four prior chemotherapy regimens before getting Adcetris, died from PML.

Siegall did confirm that a more recent, second case of PML in an Adcetris patient has been diagnosed. That case was reported to the company, which shared with the information with the FDA. He wouldn’t comment on the patient’s condition, saying that it is company policy not to talk about individual patients.

To provide some context, Siegall notes that PML is part of the underlying disease that some patients have with lymphomas. In some cases, patients get multiple rounds of chemotherapy, which suppresses their immune systems, and makes them more vulnerable to opportunistic infections like PML. He cited a May 14, 2009 article in Blood, the hematology journal, which says that between 0.07% and 0.5% of patients with blood cancers are thought to have PML.

What made the Tysabri case different is that the drug is designed to treat multiple sclerosis, a disease which isn’t normally associated with PML. Researchers now say that about 1 in 1,000 patients on Tysabri can expect to get PML. Even with that risk, the FDA has allowed the drug to stay on the market, because of the benefit it provides in reducing MS flare-ups.

Since the Seattle Genetics drug is still relatively new, it’s too early to say what kind of PML incidence rate it may have over time. What is known so far is that there are two reported cases out of more than 2,000 patients who have gotten the drug in clinical trials and in the marketplace, Siegall says. He said the Favus report was incorrect, because it said there were two PML cases of out just 410 patients.

Siegall declined to say what an acceptable PML incidence rate might be. “We have been watching this from Day 1, and we will continue to watch it,” Siegall says.

For what it’s worth, I listened to the entire FDA advisory panel proceedings over the summer during which experts reviewed the drug’s safety and effectiveness, and I don’t recall PML being raised as a point of discussion. Siegall sounded a bit irritated about the PML case coming up in the marketplace the way it did today.

“Adcetris has been used in a lot of patients, and provided an amazing opportunity for patients to get strong anti-tumor activity against fatal diseases. The testimonials I hear from families, and doctors have been overwhelming and incredibly heartwarming. I’m thrilled with the impact Adcetris has had on patients,” he says.

“As a public company CEO, I have to realize that there are some people who say things that are over-the-top positive, and some people who say things that are over-the-top negative, and incorrect. It happens,” Siegall says. “People will throw mud. I have to live with this and keep my focus on treating patients with cancer.”