Shares of Seattle Genetics Inc. leaped 17.6 percent Monday after the firm revealed striking top-line pivotal trial results showing that 75 percent of patients with relapsed-refractory Hodgkin's lymphoma (HL) receiving single agent brentuximab vedotin (SGN-35) achieved an objective response, with a median duration of more than six months.
The company's shares (NASDAQ:SGEN) closed at $14.30, a gain of $2.14.
JP Morgan analyst Cory Kasimov said the 75 percent response rate blew by his expectations. He initially assumed the bar to clear would be 40 percent or more response rate.
But the 75 percent response rate and six months plus durability "easily exceeds expectations," Kasimov said.
"These data confirm our high expectations for brentuximab vedotin," said Seattle Genetics CEO Clay Siegall. "Few agents have demonstrated this level of clinical response in a relapsed-refractory cancer setting. We are particularly encouraged by these results, given that all patients had failed multiple lines of therapy, including autologous stem cell transplant, and most had primary refractory disease."
He noted that HL affects about 8,500 people in the U.S. and about 30,000 worldwide, with about a third of those patients eventually relapsing or becoming refractory to the current four-cytotoxic drug regimen – Adriamycin (doxorubicin), bleomycin, vinblastine and dacarbazine, or ABVDs. The median survival of late-stage HL patients who fail those drugs is two to three years, Siegall said.
"There have been no major advancements in the treatment of relapsed-refractory Hodgkin lymphoma in many years," he said.
But given that Bothell, Wash.-based Seattle Genetics' pivotal trial studied "the worst of the worst population, we were very pleased to see a 75 percent objective response rate," Siegall said. He said the pivotal study's safety profile of brentuximab vedotin was "generally consistent" with prior clinical trial experience.
Siegall said his firm plans to meet with the FDA by the end of the year and remains on track to submit a biologics license application (BLA) for brentuximab vedotin, an antibody drug conjugate (ADC) targeting CD30, for the HL indication in the first half of 2011. "We are optimistic about our regulatory path forward," he said.
Seattle Genetics' partner Cambridge, Mass.-based Millennium Pharmaceuticals Inc., the oncology unit of Japanese drugmaker Takeda Pharmaceutical Co. Ltd., also intends to file a marketing application in Europe next year. Millennium paid Seattle Genetics $60 million up front in December for the rights to develop and commercialize brentuximab vedotin outside the U.S. and Canada. (See BioWorld Today, Dec. 16, 2009.)
In the U.S., Seattle Genetics plans to seek a six-month priority review and accelerated approval, Siegall told BioWorld Today. "We also continue to build our commercial infrastructure in anticipation of potential U.S. product launch in the second half of 2011," he told investors and analysts Monday during a conference call.
Even though the full details of Seattle Genetics' pivotal trial have yet to be revealed, Kasimov said he expected the FDA to put up "little resistance" in granting approval, given the strength of the top-line data, along with the unmet medical need for effective therapies in HL and the fact the company's study was conducted under a special protocol assessment (SPA) with the agency.
Brentuximab vedotin has been granted orphan drug designation by the FDA and the European Medicines Agency for the treatment of HL and anaplastic large cell lymphoma (ALCL). It also was granted fast-track designation by the FDA for HL. Seattle Genetics' single-arm pivotal trial of single-agent brentuximab vedotin was conducted in 102 relapsed or refractory, post-autologous stem cell transplant HL patients, with a primary endpoint of objective response rate as assessed by an independent review facility, Siegall explained.
Secondary endpoints included complete response rate, duration of response, progression-free survival, overall survival and tolerability. Patients in the study received 1.8 mg/kg of brentuximab vedotin every three weeks for up to 16 total dosages, Siegall added.
Seattle Genetics has yet to report what the variable rate was for the complete responses and the partial responses in its study.
"That will be reported, along with many other pieces of data, at an appropriate medical conference coming up as soon as we can," Siegall said.
Most analysts predicted those details will be presented in Orlando in December at the annual meeting of the American Society of Hematology.
Meanwhile, Siegall said the pivotal study's top-line results "move us one step closer to our goal of bringing brentuximab vedotin to patients."
Siegall insisted that the top-line pivotal results not only underscored the importance of targeting CD30 in the treatment of Hodgkin's lymphoma, but provided "strong validation" for Seattle Genetics' ADC technology.
Brentuximab vedotin is an ADC comprising an antiCD30 monoclonal antibody attached by an enzyme cleavable linker to a potent, synthetic drug payload, monomethyl auristatin E (MMAE) using Seattle Genetics' technology.
The ADC employs a linker system that is designed to be stable in the bloodstream, but release MMAE on internalization into CD30-expressing tumor cells. Seattle Genetics said that approach is aimed at sparing nontargeted cells and minimizing the potential toxic effects of traditional chemotherapy, while allowing for the selective targeting of CD30-expressing cancer cells – potentially enhancing the antitumor activity.
Within the next few weeks, Seattle Genetics also plans to report preliminary top-line data for its Phase II trial for brentuximab vedotin in ALCL, Siegall said.
"We believe that ALCL may represent an additional registration pathway for brentuximab vedotin, and we look forward to reporting these data soon," he said.
Seattle Genetics has not yet provided guidance on whether it will submit a supplemental application later to the FDA for the ALCL indication or submit it simultaneously with its Hodgkin's lymphoma.
"When the data come out, it will be informative to us," he said.
Seattle Genetics also is advancing three other brentuximab vedotin trials, including its Phase III AETHERA study of brentuximab vedotin in patients at high risk of residual HL following autologous stem cell transplant.
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