Drug companies usually have a hard time recruiting cancer patients in clinical trials, and some dirty little financial reasons for it were exposed last week in The New York Times. Another little secret is that biotech companies often overpromise, and under deliver, when they tell investors they will hit their clinical trial deadlines.
That makes it all the more surprising to hear what’s going on at Bothell, WA-based Seattle Genetics (NASDAQ:SGEN). This company, the developer of an “empowered antibody” against Hodgkin’s disease, said recently its pivotal study is recruiting patients so fast that it is now six months ahead of schedule. That sets off a chain reaction that means it should have results sooner, apply for FDA approval quicker, and reach the market six months earlier, possibly as soon as the end of 2011.
Seattle Genetics has been able to pull this off because of pent-up demand from very sick patients with relapsed forms of Hodgkin’s disease, who are searching for new treatment options. Top cancer doctors hopped on the bandwagon after the American Society of Clinical Oncology meeting in June 2008, when the company released preliminary results showing its experimental treatment was able to completely wipe out or partially shrink tumors for 12 of 38 patients, with mild to moderate fatigue, cough, and nausea as side effects. The preliminary results for brentuximab vedotin (formerly known as SGN-35) started looking even better when longer-term follow-up data was presented at a medical meeting in December.
“More investigators wanted into the trial than we could really let in to participate,” said Tom Reynolds, the chief medical officer at Seattle Genetics, in an interview on Aug. 3. “You usually have to work really hard to get them interested. There seems to be a good buzz going in the oncology community.”
Investors like it too. JP Morgan analyst Cory Kasimov, a Seattle Genetics bull, headlined his note to investors on July 23 with “SGN-35 Momentum Continues to Pick Up Steam.” Seattle Genetics seized on some of that momentum this week, raising $118 million in a stock offering that priced yesterday afternoon.
Exciting as it all was, drug development is highly regulated and slow. But Seattle Genetics has been pushing hard to move as quickly as possible. One month after producing that stellar data at the American Society of Hematology in December, Seattle Genetics clinched an agreement with the FDA on the design of the needed confirmatory trial. While negotiating with the FDA, it was getting all of its other ducks in a row, briefing doctors and nurses on what the trial design would be like, so they could hit the ground running once the FDA gave the official green light. Because of all that spadework, the full roster of 100 patients is expected to be full before the end of September.
After that, the company, doctors and patients, will simply to have to wait for a year’s worth of observations to trickle in before drawing any conclusion about whether the drug works. If the trial succeeds, Seattle Genetics will be ready to bring forward the first new treatment in 30 years for Hodgkin’s and related lymphomas, which affects an estimated 10,000 patients in the U.S.
There are many reasons why patients have flocked to the drug, Reynolds says. There’s some online buzz among patients who have heard about the provocative, if preliminary, evidence from the Phase I trial. There’s also some scientific novelty, in that this drug isn’t like a typical chemotherapy. The treatment uses an antibody designed to seek out a specific target found on cancer cells. The antibody is loaded with a potent toxin to give it extra tumor-killing punch.
Convenience also helps. The drug only needs to be infused once every three weeks, making it manageable for patients who travel long distances to see their doctor. There aren’t many competing drugmakers trying to enroll these same patients in a trial, other than Novartis, which is studying panobinostat, Reynolds says. And, the Seattle Genetics trial is designed so that all patients who enroll are guaranteed to get the experimental medicine—there’s no 50-50 shot that patients will randomly get stuck with a placebo, or a lackluster regimen of standard chemotherapy.
This means the Seattle Genetics trial doesn’t meet the usual gold standard of medical evidence for comparison—in which patients with similar characteristics are randomly assigned to get an experimental drug or the existing standard of care. But cancer drugmakers sometimes try to avoid this design, because they think they can save time and money with a simpler trial, while still getting a definitive answer on whether their experimental drug is any good.
When asked if the single-arm nature of the study helped speed up enrollment, Reynolds says, “it certainly doesn’t hurt.”
Seattle Genetics says it gave a lot of thought to the pros and cons of different trial designs. It consulted with many of thought leaders who treat Hodgkin’s patients, as well as the FDA, Reynolds says. The company concluded it wasn’t necessary to run a randomized trial because the only treatment options left for these patients offers slim odds of shrinking tumors and don’t provide lasting benefits. Until brentuximab vedotin (SGN-35) came along, nothing really had changed in standard practice for 30 years. Life expectancy for relapsed patients following a bone marrow transplant was predictable, at about 2.5 years, Reynolds says.
“If we see something similar to what we saw in Phase I, that will be unquestioned data,” Reynolds says. “We believe this pivotal trial, on its own, will be sufficient for accelerated approval.”
Yet when a trial enrolls this fast, I have to wonder whether there are any special pitfalls to watch for. Might doctors get over exuberant, and recruit a hodgepodge of patients, some of whom don’t belong in the study? Are doctors succumbing to bias, and cherry-picking some healthier patients to try to make the drug look better than it is? These are familiar concerns to any trial, and it’s Reynolds job to make sure that doesn’t happen. “We’ve been extremely stringent on the inclusion and exclusion criteria. There are no exceptions,” Reynolds says.
Then again, there are few situations in which experimental cancer drug trials enroll so fast. It happened at least a couple times in the past decade, Reynolds says, with Takeda Pharmaceuticals’ bortezomib (Velcade) for multiple myeloma, and Novartis imatinib (Gleevec) for chronic myeloid leukemia.
Those drugs were such big leaps over the prior standards of treatment that they generated standing ovations at medical meetings. Today both generate more than $1 billion in annual sales. Seattle Genetics has a long road to reach that destination, but in my profile of Reynolds last fall, he said the data on brentuximab vedotin have a lot of similarities with the headliners of the recent past. “It sounds like Gleevec. It sounds like Rituxan,” he said last September.
He didn’t have quite such a zinger ready when we talked last week, but he didn’t back off in his prediction for success, either.”The biggest winners will be the patients,” Reynolds says.
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