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 that 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 next week, may allow Osaka, Japan-based Takeda and Seattle Genetics, of Bothell, Washington, 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 Kantor, who is based in San Francisco, 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 an interview.
Roche Drug Denied
In August, the FDA declined a request by Basel, Switzerland-based Roche, the world’s biggest maker of cancer drugs, and its partner, Waltham, Massachusetts-based Immunogen Inc., 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, Krysta Pellegrino, a spokeswoman for Roche’s Genentech unit, based in South San Francisco, California, said in an e-mail.
Seattle Genetics rose 12 cents, or less than a percent, to $15.22 at 4 p.m. New York time in Nasdaq Stock Market trading. The shares have surged 25 percent since preliminary results on the lymphoma studies were announced before the start of trading on Sept. 27, and 57 percent in 12 months.
Those 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.
‘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 in Seattle, 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, 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.”
Woman in Remission
Among the patients was a 19-year-old woman who’d been told she was likely to die. She’s now in remission, Shustov said. He will present detailed results on all 58 patients at the annual meeting of the American Society of Hematology, beginning Dec. 4 in Orlando, Florida.
SGN-35 also was tested in 102 patients with a more common condition called 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, which also will be presented at the hematology meeting, 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, California, and a consultant for Seattle Genetics.
Seattle Genetics and other partners are also testing different antibody-drug combinations for treating cancers of the kidney, prostate, pancreas and other organs. The allies include Roche’s Genentech unit; Bayer AG of Leverkusen, Germany; Celldex Therapeutics Inc. of Needham, Massachusetts; Daiichi Sankyo Co. of Tokyo; GlaxoSmithKline Plc of London; AstraZeneca Plc of London, and Astellas Pharma Inc. of Tokyo.
Seattle Genetics’ experimental SGN-35 won’t be the first drug in this therapy family to make it to market. Mylotarg, developed by Wyeth, was removed from the market in June by New York-based Pfizer Inc., which acquired Wyeth last year. Studies showed that the medicine didn’t benefit patients with leukemia and was linked to deaths from liver and lung complications.
Mylotarg’s side effects are thought to have been caused by the failure of the linker to hold onto its cancer-killing payload, said Fred Jacobson, a Genentech scientist, said in an interview.
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