Seattle Genetics Gains Another FDA Approval

FDA Approval

Seattle Genetics, Inc. announced that the U.S. Food and Drug Administration (FDA) had approved its Adcetris (brentuximab vedotin) in combination with chemotherapy in adults with previously untreated Stage III or IV classical Hodgkin lymphoma. This is the fifth approval for the drug, and some analysts predict it will edge ever-closer to blockbuster status—$1 billion in annual sales—but some, as well as some oncologists, are skeptical.

It’s the first FDA approval for advanced Hodgkin lymphoma in more than 40 years, a fact the agency seems eager to publicize. Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a statement, “This approval demonstrates our commitment to approving advances in treatment that give prescribers and patients different options for care.”

The approval was based on data from the Phase III ECHELON-1 clinical trial that compared Adcetris and adriamycin, vinblastine and dacarbazine (AVD) to adriamycin, bleomycin, vinblastine and dacarbazine (ABVD). That data was presented at the 59th American Society of Hematology (ASH) annual meeting in December 2017, along with publication in the New England Journal of Medicine.

The two-year modified progression-free survival rate with the drug was 82.1 percent compared to 77.2 percent in the control arm, or a 6 percent improvement, as presented as Clay Siegall, the company’s chief executive officer, at ASH. John Carroll, with Endpoints News, writes, “More patients would be given an opportunity to find a curative solution, said Siegall, even though there was no significant overall survival benefit in the data package for the combination of Adcetris and chemo. And patients could drop the toxic bleomycin from the standard chemo combo used to treat the disease. Analysts tended to diss the results as relatively modest, and lymphoma expert John Leonard noted at the time that most patients will be able to drop bleomycin after the second cycle in any case, citing a study called RATHL.”

Investors apparently were not dazzled by the news, either. Shares dropped slightly. Some analysts believe the investors were disappointed Adcetris wasn’t approved for broader use in less advanced cases of lymphoma.

Still, PMLive notes, “Approval in the new indication is an important pillar in Seattle’s plans for Adcetris, which made $640 million in revenues last year worldwide, with some of that booked by Takeda Pharmaceutical which has rights to the drug outside the U.S. and Canada. According to the FDA, there were around 8,260 people diagnosed with Hodgkin’s lymphoma last year.”

Adcetris is an anti-CD30 monoclonal antibody attached to a microtubule disrupting agent, monomethyl auristatin E (MMAE). It was first approved in 2011 for Hodgkin’s lymphoma in patients who failed a stem cell transplant. It is being evaluated in more than 70 clinical trials, including two ongoing Phase III studies, the ECHELON-2 trial in frontline mature T-cell lymphomas and the CHECKMATE 812 trial of the drug in combination with Bristol-Myers Squibb Company’s Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

The drug comes with a boxed warning highlighting the risk of John Cunningham virus infection that can result in progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can be lethal. Serious adverse effects include peripheral neuropathy, severe allergic reactions, blood, lung and liver toxicities, opportunistic infections, tumor lysis syndrome, and serious dermatologic reactions and gastrointestinal complications.

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