Some of the best-selling drugs in the pharmaceutical industry are what biotechies call “naked” antibodies. These are engineered Y-shaped proteins that zero in on markers of diseased cells, while sparing healthy ones. They generate an estimated $30 billion in annual sales, from big names like Roche’s trastuzumab (Herceptin) for breast cancer.
But to hear one of the nation’s leading developers of antibody drugs talk today, those treatments aren’t really on the cutting edge anymore.
“It’s unlikely in the future of Seattle Genetics that we’ll put another naked antibody into the clinic,” CEO Clay Siegall says. “The future will be with antibodies that are empowered.”
Seattle Genetics (NASDAQ: SGEN) has come to that conclusion after it has spent more than a decade trying to make antibodies more potent. The company, founded in 1998, has never been able to take a naked antibody drug all the way through to FDA approval, and it has shelved a number of candidates over the years—SGN-10, SGN-15, SGN-30. But Seattle Genetics has generated its most promising data yet from a next-generation “empowered” antibody for Hodgkin’s disease. The technology that makes this possible—linking a regular antibody to a toxin that can give it extra-tumor killing punch—has now been licensed to eight other drug companies. More data emerged this year from competitors Roche and ImmunoGen that suggests they, too, have found a way to link an antibody with a toxin to create a souped-up antibody drug that beats the original. And Seattle Genetics has designs on pushing the envelope further in the future with another next-generation technique for making antibodies more potent.
Scientists have been dreaming about creating powerful targeted therapies, known as antibody-drug conjugates, for three decades, but the efforts usually failed because the linkers weren’t stable, and the toxins broke off in the bloodstream before they could reach the intended target, causing side effects. Seattle Genetics’ technology is built on the idea that its synthetic linkers remain stable until the antibody reaches the tumor and unleashes its toxic payload.
The lead drug candidate at Seattle Genetics, brentuximab vedotin, opened the eyes of cancer researchers a little more than a year ago with its data. Scientists said that 17 of the 44 patients (38 percent) had their tumors completely disappear or mostly go away after they took the drug. When they looked at patients who got higher doses that are more likely to be tested in late stages, the data look even better. Of the 28 patients who got those doses, about one-third had their tumors completely disappear, while 93 percent had at least some measurable tumor shrinkage. That drug is now in a pivotal clinical trial that could produce results by the end of this year, and may reach the U.S. market by the end of 2011.
While Seattle Genetics still has a couple of naked antibodies moving through clinical trials, Wall Street isn’t counting on them. Last month, Roche pulled the plug on a partnership to develop … Next Page »