After years of plugging away at antibody-drug conjugates, Seattle Genetics has finally secured significant validation for its technology. This morning, Seattle-based biotech announced impressive results from a pivotal trial of brentuximab vedotin, an anti-CD30 antibody linked to an auristatin, a small molecule that blocks the formation of microtubules.
Brentuximab, also known as SGN-35, shrank or got rid of tumors in 75% of Hodgkin’s lymphoma patients who had failed to respond to other treatments. Further, that response to SGN-35 lasted for over six months in many of those patients. In this patient population, medical experts had felt that anything more than a 30% response rate would have been solid, Needham & Co. analyst Mark Monane said in a note to investors.
The results “underscore the importance of targeting CD30 in the treatment of Hodgkin’s lymphoma and provide strong validation for our proprietary antibody-drug conjugate technology,” Seattle Genetics’ CEO Clay Seagall said in a conference call this morning.
With today’s data, Seattle Genetics appears to be succeeding in an area that has proven challenging for many. In theory, designing an antibody-drug conjugate (ADC) is straightforward: tether a powerful chemotherapeutic to a cell-specific antibody that can deliver it directly to tumors. And voila, the therapeutic window is opened on chemo drugs that are excellent cancer killers but too toxic to healthy cells.
But developing an ADC has turned out to be tougher than anticipated. The biggest hurdle for scientists has been finding the right link between the antibody and the small molecule–the link after all enables scientists to control where and when that toxic payload is released. Most companies have used pH as the trigger for release, an approach that has proven to be too promiscuous; if the ADC wanders into the wrong environment with the right pH, the cytotoxic drug would get released, damaging healthy cells. Wyeth’s Mylotarg, the first and only ADC to be approved, was taken off the market this summer after it was found to cause more deaths than chemotherapy alone. Most view the unstable linker as the culprit behind Mylotarg’s safety issues.
Based on today’s positive data, Seattle Genetics seems to have overcome that challenge. For SGN-35, the biotech uses a linker that is snipped by cathepsin C, an enzyme found inside cells that is turned on an off based on pH. Even if some cathepsin C is in the bloodstream, the cytotoxic molecule won’t be released because the pH is too low.
Seattle Genetics and Millennium expect to file for U.S. regulatory approval for SGN-35 in the first half of 2011. FDA granted the drug fast-track status in Hodgkins’ lymphoma, meaning U.S. approval could come in the second half of 2011. Meanwhile, the company will soon announce pivotal data for the drug in anaplastic large cell lymphoma.
Although the patient population for both types of lymphoma are relatively small, Needham & Co.’s Monane still expects the drug could bring in $400 to $500 million in Hodgkin’s lymphoma alone. In a note to investors, Monane said the drug has the potential to deeply penetrate the market and be used for an extended period of time.
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