The last time the phone rang this much at Seattle Genetics, the company parlayed enthusiasm about one of its drug candidates into a partnership with Genentech potentially worth more than $800 million. This time, after 10 years in business, the Bothell, WA-based company thinks it may have the first drug it can take all the way to the market on its own.
“We’ve reached the tipping point, where we are no longer calling around and asking top clinicians to join our studies,” said Seattle Genetics CEO Clay Siegall. “They’re calling us.”
The fuss is coming from findings presented this month at two big cancer meetings on the company’s “empowered antibody,” SGN-35. A trial of 38 patients with Hodgkin’s disease and related forms of lymphoma found the drug completely wiped out or significantly shrank tumors for patients who had relapsed following an average of three rounds of chemotherapy. Five patients had their tumors completely disappear, while seven had their tumors shrink by more than 30 percent after taking the drug. Side effects were mostly mild to moderate fatigue, cough and nausea, researchers said.
“It’s rare in a Phase I study to see 12 objective responses,” Siegall said. “Often we’re happy enough with two or three to go on to Phase II.”
It’s a big step forward for a small company, which hasn’t yet moved one of its candidates into the final stage of clinical trials, much less brought one to the market. It also could be a groundbreaking moment for an emerging class of cancer drugs, known to scientists as “antibody-drug conjugates,” that have been a dream of Seattle Genetics since its founding, and for cancer researchers worldwide for more than 30 years.
The idea is to develop an engineered antibody that can seek out cancer in the body, avoiding healthy tissues, and dump a lethal dose of chemotherapy inside the tumor cells. The biggest-selling products in cancer treatment today, Genentech’s Avastin and Rituxan, are engineered antibodies that hit a specific target on cells, yet they aren’t attached to toxic chemotherapy payloads that could give them more punch.
SGN-35 uses a similar antibody to carry such a payload to a target found on Hodgkin’s disease cells and rarely seen on healthy cells. Most previous attempts to “empower” antibodies failed in the past because the chemotherapy molecules broke off and started floating around the bloodstream. That meant the drug never got to the right place, and the treatment caused similar side effects to standard chemotherapy.
One of Seattle Genetics’ innovations was to develop a synthetic linker to connect the antibody to a potent cell-killing toxin. The linker is designed to hold the antibody and toxin together as a stable package in the bloodstream, until it can be absorbed inside tumors, where it runs into enzymes that chop the toxin loose to do its damage. The technology has been licensed by some big names in biotech, including Genentech, MedImmune, Bayer, and Progenics.
“They are in a fabulous strategic position,” said David Miller, president of Biotech Stock Research, an independent research firm in Seattle that follows the company. “They have money in the bank, and more coming from Genentech. The data from this next trial could be taken to the FDA. The drug would sell itself, you wouldn’t need a large sales force.”
A lot still needs to be done to get the drug to market, though, meaning a lot could still go wrong. Seattle Genetics is still working on its game plan for what comes next with SGN-35, Siegall said. The company is negotiating with the FDA on the design of a couple of clinical trials that could offer proof the drug is good enough for approval. Siegall isn’t saying exactly what the trials will look like, but one for Hodgkin’s disease will probably enroll more than 100 patients and one for related T-cell lymphomas could enroll fewer than 100, he said. It’s possible the agency may not require the trials to be randomized, placebo-controlled studies—the gold standard of medical evidence—because there are no standard therapies for relapsed patients against which the drug could be compared, Siegall says.
That might make interpreting the results more difficult, but such a trial would likely speed up enrollment since patients wouldn’t worry about possibly getting stuck with little hope in a control group. Another thing that could speed the studies is if the FDA didn’t require Seattle Genetics to prove SGN-35 prolongs lives—which can also take years—but rather was satisfied with a surrogate measurement of effectiveness, like tumor shrinkage or a reduced rate of disease spread. Siegall wouldn’t say which way he thought the FDA was leaning on this question.
The company expects to announce what the trials will look like by the end of this year, he says. If all goes perfectly—always a big-time if in biotech—Seattle Genetics could start the studies in early 2009 and send the results to the FDA for approval in 2011.
Before that happens, potential partners apparently want their piece of the action. More than 10 large drugmakers have called to ask about a partnerships, Siegall says. The company has decided it will consider doing a deal outside the U.S. for SGN-35, which may also include one of its other products in development, he said.
The opportunity doesn’t appear to be as big for SGN-35 as for an antibody like Avastin, that chokes off blood supply to multiple kinds of tumors. An estimated 6,000 to 8,000 patients in the U.S. and Europe get the type of disease treated by SGN-35, according to Seattle Genetics market research. At a price of $45,000 to $50,000 per year for the drug, it could generate $300 million to $400 million in sales, Siegall said.
Sales would go higher than that if doctors can show, as they are strategizing to do right now, that the drug may work for patients with earlier stages of Hodgkin’s and various lymphomas. If that happens, the company might need to hire another person to answer the phones.
