Seattle Genetics, Millennium’s Encore: Souped-Up Antibody Looks Better in 2nd Trial

Seattle Genetics generated buzz at a medical meeting over the weekend with its new souped-up antibody drug for Hodgkin’s disease, and today it is coming out with an encore that tops the original performance.

The biotech company (NASDAQ: SGEN) and its partner, Cambridge, MA-based Millennium: The Takeda Oncology Company, are presenting results today from a study of 58 patients who got the targeted drug for a rare and deadly malignancy called anaplastic large cell lymphoma (ALCL). More than half of the patients (53 percent) had their tumors completely eradicated after getting dosed with brentuximab vedotin, and a total of 86 percent had their tumors shrink by half or more, according to findings being presented today at the American Society of Hematology (ASH) meeting in Orlando, FL.

The most common severe side effect, in one-fifth of patients, was neutropenia, in which infection-fighting white blood cells get knocked out. Doctors don’t know how long the remissions are lasting, because more than half of patients are still in remission after six months of follow-up.

“Nearly all patients in this trial had reductions in tumor volume, including a remarkable rate of complete remissions,” said Dr. Andrei Shustov, a hematologist at the University of Washington, in a Seattle Genetics statement. Another researcher, Pier Zinzani of Seràgnoli University of Bologna, Italy, noted that since this drug was given by itself, with no other chemotherapy combinations, it was particularly impressive. “Single-agent activity of this magnitude is rarely seen in oncology,” he said in a statement.

This is the second important batch of clinical trial results for this drug at this year’s hematology meeting. On Sunday, researchers reported that the new drug generated complete remissions in about one-third of patients with Hodgkin’s disease, and shrank tumors by half or more in another 40 percent of patients. Those results, combined with the new findings among patients with the related malignancy known as ALCL, have given Seattle Genetics the confidence to seek FDA approval before the end of March for brentuximab vedotin for both forms of cancer. If approved, it will be the first marketable product for Seattle Genetics, and it will be the only drug available that combines the specific tumor-targeting capability of an antibody with an extra-potent dose of a toxin to give it extra tumor-killing kick.

Seattle Genetics CEO Clay Siegall

Seattle Genetics CEO Clay Siegall

Investors have been hotly anticipating this data set ever since Seattle Genetics offered a basic preview press release on the trials, back in September and October. Since investors already bid up Seattle Genetics shares more than 56 percent heading into the weekend’s detailed data dump, there was a sell-on-the-news reaction yesterday, in which the stock dropped about 4 percent.

“Overall, we believe the results are very good, and that this drug is exceedingly likely to be approved in the second half of 2011,” said Cory Kasimov, an analyst with JP Morgan, in a note to clients after the Hodgkin’s data was reported on Sunday. “However, considering that prevailing expectations were already quite high, we suspect it will be difficult for this weekend’s update to trigger near-term upside in Seattle Genetics shares.”

Here’s what the latest study showed of the new drug. The 58 patients who enrolled had relapsed or treatment-resistant forms of anaplastic large cell lymphoma (ALCL), and they all got an intravenous infusion of brentuximab vedotin by itself once every three weeks, for a maximum of 16 doses. The main goal was to see whether it could at least partially, or completely shrink patients’ tumors when scrutinized by independent review of medical images. The patients’ median age was 52, and because of their severe disease, had a life expectancy of between one and two years, according to Seattle Genetics CEO Clay Siegall.

Researchers found that 50 of 58 patients (86 percent) had their tumors shrink by at least half, and 97 percent had at least some observable shrinkage of their tumors. Like the researchers said, that is a very encouraging early sign for a cancer drug, especially in such a sick group of patients. But it will take a lot of follow up time to see how long those remissions really last, and whether it actually translates into the gold standard of success for a cancer drug, which is to help patients live longer. Researchers are continuing to follow up patients to get answers to both of those questions, Siegall says.

The most common side effects in patients were nausea (38 percent), peripheral neuropathy in which patients get numbness and tingling in the fingers and toes (38 percent), fatigue (34 percent), fever (33 percent) and diarrhea (29 percent).

If this drug is approved, it would clearly be used by a small number of patients. About 2,000 adults in the U.S. each year are thought to have anaplastic large cell lymphoma. That’s roughly 3 percent of the 65,540 Americans diagnosed annually with non-Hodgkin’s lymphoma. About two-thirds of the 8,500 patients diagnosed with Hodgkin’s each year are successfully treated with chemotherapy upfront, meaning about one-third eventually relapse and would be candidates for the brentuximab vedotin therapy. The drug is designed to work by hitting a protein target known as CD30 that is commonly found on tumors of patients with both Hodgkin’s and anaplastic large cell lymphoma.

Researchers are now studying whether patients can see even more benefit by getting the Seattle Genetics drug with earlier forms of disease, and whether it might be useful in preventing relapses.

Seattle Genetics hasn’t set a price for this product—that will come only if it wins FDA approval—but analysts are already sketching out their financial forecasts. Kasimov, in his note to clients yesterday, said that brentuximab vedotin has about an 85 percent chance of winning FDA approval, and generating peak U.S. sales of about $225 million in 2015.

While the data certainly impressed one of the medical investigators I talked to—Robert Chen of the City of Hope—Seattle Genetics will need to do more to keep investors happy. It will need to show that it can fully maximize the opportunity in patients with Hodgkin’s disease and anaplastic large cell lymphoma, and then start branching out into other rare lymphomas where CD30 is a logical target. Even more importantly, it will have to show that it has solved the three-decade long technical challenge of combining antibodies with toxins to make them more potent, and that brentuximab vedotin is really just a harbinger of similar drugs to come.

Siegall, when we spoke on the Thursday prior to the ASH conference, said he expects his company to deliver on all of the above.

“Few agents I’ve seen in my career can deliver this kind of anti-tumor response,” Siegall says. “It’s a strong validation of our platform.”

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