CHICAGO–The FDA’s oncology chief, Richard Pazdur, used his turn in front of the press mob at ASCO today to make some very public vows about his commitment to the newly launched breakthrough-drug program, that intriguing new classification for certain stellar therapeutic programs that will be extended VIP status at the agency.
Pazdur stressed that any drug development team working on a breakthrough drug will have no trouble getting steady feedback from the agency, and in particular the oncology division he runs. Pazdur and the agency view these drugs as potentially “transformative” therapies capable of changing the course of patients’ lives. And the agency is committed to spending time in an “iterative fashion,” holding monthly meetings and teleconferences to advise teams on accelerating the whole development process, with a goal of quickening final marketing decisions.
This is going to be a “different communication structure,” Pazdur promises, “with much more of a continuous dialogue with sponsors.” Together, regulators and development teams can change endpoints, downsize trial sizes in light of the data they’re seeing and expedite reviews–adaptive research with regulatory input.
For an industry that broadly views drug development as a 10-year process that can consume an average of a billion dollars per success story, this is big stuff.
But the breakthrough designation seems to have stirred up equal amounts of skepticism and hope in the biopharma community. Still in its early days, I’ve been studying each announcement for some sign of who’s likely to get the backstage pass at the FDA and what it means in real terms. In drug development, and particularly in the cancer field, the focus now is on carving years out of the development process. So if Pazdur’s serious–and there’s no mistaking his public commitment–there’s potential here to do some game-changing redesigns of the clinical trial process.
The FDA, though, can only help. This R&D revolution is being driven by major players, and they’re already changing the way cancer drugs are developed. Earlier today I was talking to Dr. Nancy Valente, the senior clinician heading up Genentech’s hematology franchise, who’s been involved in the development of obinutuzumab or GA101, a fascinating new therapy that applied some intriguing glycoengineering technology to craft an antibody that could directly terminate cancer cells at the same time it spurs the immune system to send its own killer team to participate in the massacre. That kind of immunotherapy-plus process has produced some outstanding progression-free survival data, giving Roche ($RHHBY) a good shot at coming up with a superior successor to Rituxan, a drug that earned about $7 billion last year.
At the time Roche started its randomized Phase III study, they had data on only 33 patients, including some mid-stage single-arm results. Investigators started off by testing six patients to see if there were any big red safety flags that would prevent testing, then pushed ahead and essentially cut out the randomized Phase II study that has long been a standard trial feature. At the beginning of the clinical program, investigators paid especially close attention to side effects to make sure they hadn’t overlooked anything in the abbreviated safety study.
Doing that cut anywhere from two to three years out of the development process, says Valente. The clinical program, from first dosing to its first regulatory filing, took less than 6 years.
It’s no surprise GA101 is one of the 8 experimental cancer drugs to win the breakthrough designation. Of course, word of that only came down a couple of weeks ago, so no one on the Roche/Genentech side has had much of a chance to determine exactly how breakthrough status is going to change things. The drug has already been filed for an approval for CLL, but there are also follow-up studies underway for non-Hodgkin’s lymphoma.
Roche is one of a number of major pharma players to win this designation, underscoring that Pazdur initially is going to be most comfortable handing out breakthrough passes to the deep-pocket outfits he’s worked with for years. Trust goes a long way in any field. In drug development, it’s crucial. And with Pazdur, it’s critical. Anyone who follows the drug approval process knows Pazdur can make or break a drug, and he personally won’t hesitate to come out swinging during a panel review if he’s already made his decision to squash an application (just ask Aveo).
That kind of commitment indicates that Pazdur will keep his promises on shepherding the drugs he believes qualify as breakthrough drugs. Conversely, rival developers excluded from the VIP crowd are likely to view the designation as rank favoritism. And they may find it tougher than ever to win an audience with regulators, let alone an approval. That may be particularly worrisome for smaller companies looking to pioneer a new therapy, especially without that regular feedback that Pazdur’s team is directing elsewhere.
What the FDA gives with one hand, it can take away with the other. And we’ll keep looking to see how this plays out.