Seattle Genetics & ImmunoGen on a Roll
Oct11

Seattle Genetics & ImmunoGen on a Roll

The good news keeps coming for companies developing antibody-drug conjugates, which enable the targeted delivery of powerful chemo drugs. (click here for more info on how they work). On the clinical side, ImmunoGen and Roche have released a promising set of data for T-DM1, their drug linking trastuzumab with DM1, a derivative of the microtubule-disrupting agent maytansine, while Seattle Genetics and Millennium Pharmaceuticals offered the latest validation for SGN-35. Meanwhile, ImmunoGen sealed a deal with Novartis worth up to $240 million. First to the clinical results: Although the trial was relatively small, ImmunoGen’s T-DM1 appeared to be as good at shrinking tumors as a combination of Herceptin and chemotherapy in patients with HER-2 positive, metastatic breast cancer. Importantly, patients in the T-DM1 arm experience significantly milder side effects than those taking the Herceptin/chemo combo. For example, 66.2% of patients in the chemo arm experienced complete hair loss, compared to 1.5% in the T-DM1 arm, and 57.4% of the Herceptin/chemo patients experienced neutropenia, or white blood cell count lowering, vs. 7.5% of the patients in the T-DM1 arm. In a note to investors, RBC Capital Markets’ analyst Jason Cantor called the results “particularly groundbreaking” because no chemotherapy drug was added into the T-DM1 treatment arm. The trial “is significant validation of ImmunoGen’s technology and antibody-drug conjugation technology, in general.” In August, ImmmunoGen and Roche had a setback when after FDA refused to accept their biologics license application for T-DM1 based on the Phase II data offered up in the filing. Roche had already started a Phase III study, and Cantor expects Roche to try again with FDA in mid-2012, putting a potential launch in the first half of 2013. The positive data for T-DM1 comes on the heels of strong results for Seattle Genetics’ antibody-drug conjugate, SGN-35. Last month, the Seattle-based biotech said the drug was able to shrink tumors in 75% of people with Hodgkin’s lymphoma who had failed to see results with other treatments. Seattle Genetics expects to file a BLA for SGN-35 in the first half of 2011, with approval expected in the second half of the year. Today, Seattle Genetics and Millennium said that SGN-35 shrank all or some tumors in 86% of patients with anaplastic large-cell lymphoma. Look for more data in both Hodgkin’s lymphoma and in ALCL in December during the American Society of Hematology annual meeting. On the deal front, Novartis is coughing up $45 million upfront and up to $200 million in milestones to apply ImmunoGen’s antibody-drug conjugate technology (which it calls “TAP” for targeted antibody payload) to a select number of targets. ImmunoGen could also score research funding and additional support if...

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Seattle Genetics’ Brentuximab Validates ADC Approach
Sep27

Seattle Genetics’ Brentuximab Validates ADC Approach

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...

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