The FDA may be creating expectations among seriously ill patients that are unlikely to be fulfilled by designating new cancer drugs as breakthrough therapies, a Harvard Medical School faculty member told Bloomberg Law.
Jonathan J. Darrow was taking aim at an almost six-year-old program that allows drug companies to get their medicines reviewed by the Food and Drug Administration more quickly—if a drug treats a serious medical condition, and if it can demonstrate substantial improvement over existing therapies. The FDA’s breakthrough therapy program is shaving about two years off the time it takes for these drugs to get on the market, but benefits to the patient weren’t statistically significantly better compared to drugs approved through the normal drug approval channels, according to a study Darrow co-authored.
“To the extent that the drugs that do come out of that program are better than existing treatments and do benefit patients, those speedier approvals could be important because it means patients get the drugs more quickly,” Darrow, a faculty member at both Harvard Medical School and Brigham and Women’s Hospital, said in a May 2 interview. “The concern is that if these drugs are getting approved more quickly but they don’t benefit patients very much.”
Use of the term “breakthrough” could be misleading, and the earlier approval isn’t conferring much or any advantages in those cases, he said.
Breakthrough is one of several possible channels drug companies can use to cut to the head of the line for the FDA to review new drug applications, including accelerated approval and priority review. There’s a growing number of companies seeking the breakthrough designation, according to data from the FDA. Drugs such as AstraZeneca’s Calquence (acalabrutinib) in October 2017 and Pfizer Inc.’s meningitis B vaccine Trumenba (meningococcal group B vaccine) are among the 91 drugs the FDA has approved using breakthrough review, according to data compiled by the Friends of Cancer Research through April 27. The Friends data show the FDA has granted the breakthrough designation to 210 of the 603 requests it has received since 2012.
Cancer treatments comprise about half of those, Darrow said. From 2012 to 2017, the FDA approved 58 new cancer drugs, 25 of which received the designation, Darrow and his co-authors found. While they found shorter approval times, they said, there was no statistically significant difference in measurements such as length of time a patient lives with the disease but it doesn’t get worse. “Based on the data that’s available, there’s no statistically significant difference in breakthrough versus non-breakthrough drug in terms of benefit.”
The paper, “Efficacy, Safety, and Regulatory Approval of Food and Drug Administration–Designated Breakthrough and Nonbreakthrough Cancer Medicines,” isn’t the first time Darrow and Aaron S. Kesselheim have been critical of the breakthrough program. They co-authored a 2014 New England Journal of Medicine paper that expressed concern this designation continues a trend of “applying increasingly flexible evidentiary standards to determine the qualification for expedited development and approval programs.”
Friends Counters Conclusions
A 2011 conference co-hosted by Friends of Cancer Research spurred the breakthrough designation proposal that eventually made its way into the 2012 Food and Drug Administration Safety and Innovation Act. Jeff Allen, chief executive officer of Friends, said the importance of getting those drugs on the market two years ahead of time shouldn’t be overlooked. “That’s the point of the designation—if a drug shows early potential to treat a previously untreatable illness, can development be sped up without compromise? According to this study, the answer is ‘yes,’” Allen wrote in a May 2 email to Bloomberg Law.
Many of the drugs designated breakthrough represent treatments for patients who otherwise had limited to no options, Allen added. “An effective drug in this context warrants that steps be taken to provide rapid access. How a drug to treat one disease compares to drugs used to treat completely unrelated types of cancer is sort of irrelevant.”
An FDA spokeswoman told Bloomberg Law the agency will review the paper. The FDA generally doesn’t comment on specific studies, but evaluates them “as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
Reproduced with permission. May 2, 2018. Copyright 2018 by The Bureau of National Affairs, Inc. (800-372-1033) <http://www.bna.com>