Seattle Genetics team may win clearance for anti-cancer drug

Seattle Genetics and Takeda Pharmaceutical may beat Roche Holding in developing a new type of combination cancer therapy that's less toxic than standard treatments.

The product, SGN-35, uses an antibody that recognizes and connects to receptors found only on the surface of malignant cells. Once there, the therapy releases a powerful chemical called auristatin, which kills cancer cells by stopping them from dividing. By keeping that drug out of the bloodstream and away from healthy tissue, the treatment avoids the side effects of standard chemotherapy.

Two studies on SGN-35's use in lymphoma, to be reported at a medical meeting this week, may allow Osaka, Japan-based Takeda and Bothell-based Seattle Genetics to win U.S. clearance a year before Roche's similar therapy, called T-DM1. If approved, SGN-35 may generate $420 million in annual revenue by 2015, said Jason Kantor, an analyst at RBC Capital Markets.

The two drugs "are the tip of an iceberg," said the San Francisco-based Kantor in a telephone interview. "Once one of these drugs proves itself clinically and is approved, we're going to see many more over the next three to five years. And they will have a meaningful impact on cancer treatment."

Seattle Genetics, which has no marketed products, plans to apply to the U.S. Food and Drug Administration for conditional approval of SGN-35 in the first half of 2011, said Chairman and Chief Executive Officer Clay Siegall. That process would allow the drug to be used while the company conducts confirmatory studies. If the agency agrees, SGN-35 may be in doctors' hands by the end of 2011, Siegall said.

In August, the FDA declined a request by Basel, Switzerland-based Roche, the world's biggest maker of cancer drugs, and its partner, Waltham, Mass.-based Immunogen, to approve T-DM1, a souped-up version of its breast-cancer therapy Herceptin, on an accelerated basis. The agency said the application didn't meet the criteria because other therapies for breast cancer are available to patients, according to Roche.

Roche may file a new application in 2012, said Krysta Pellegrino, a spokeswoman for Roche's Genentech unit, based in South San Francisco, Calif.

Drug called potent

The initial results showed the drug was "very potent" and provide the basis for Seattle Genetics to seek U.S. clearance, Kantor said. While approval would come first for patients who weren't cured by other therapies, the drug eventually may gain wider use if it proves itself as a first-line treatment, he said.

The new combination drugs have three key components: an antibody, a cancer-killing drug, and a Velcro-like substance, known as a linker, that holds the two tightly together so they don't separate in the bloodstream. After the antibody finds and binds to its target, the linker loosens its grip and dumps the drug in the cell, where it attacks from within.

Because the medications deliver their chemical payloads only to the tumor, they can be given at high doses and still avoid the side effects that can make chemotherapy miserable for many patients, said Hope Rugo, a breast-cancer specialist at the University of California, San Francisco.

"Could bring a real change"

"If this approach pans out, it could bring a real change in the way we think about delivering treatment," Rugo said in a telephone interview. "It's a perfect scenario for how you could kill cancer and not cause so much systemic toxicity."

Andrei Shustov, a blood-cancer specialist at the University of Washington, led a trial of patients who had relapsed after being treated for anaplastic large-cell lymphoma, a rare and aggressive type of T-cell lymphoma. Lymphomas attack the lymphatic system, part of the body's disease-fighting system.

Shustov and his colleagues gave as many as 16 rounds of SGN-35 to 58 patients. In the first group of 30 people, 57 percent had a complete response, meaning their cancer was undetectable, and 30 percent had less cancer in their system.

"In treating T-cell lymphomas for the past five years, I have never seen activity even approaching the efficacy of SGN- 35," Shustov said. "I believe this is a major breakthrough in T-cell lymphoma therapy."

Patient is in remission

Among the patients was a 19-year-old woman who had been told she was likely to die. She's now in remission, Shustov said. SGN-35 also was tested in 102 patients with Hodgkin's lymphoma.

While Hodgkin's is often curable, the people in the study were drawn from the 15 percent of patients who didn't improve on chemotherapy and had poor prospects for survival.

Initial results of the trial showed that the tumors shrank in 97 percent of patients, and symptoms disappeared in 83 percent.

"This is unheard of for a single drug," said Robert Chen, the study's lead researcher. "Within a week, you could see some patients get better." With SGN-35, "you're going to see more cures, and you're going to buy a lot more time for patients who previously were destined for hospice."

Chen is an assistant professor at the City of Hope, a nonprofit cancer center in Duarte, Calif., and a consultant for Seattle Genetics.