Dr. Ken’s Corner: Be Wary of FDA-Designated Breakthrough Drugs

When the FDA says a new drug is a “breakthrough,” does that mean it’s clearly better than what’s already out there?

Since 2012, the FDA has been empowered by Congress to label a drug as a “breakthrough therapy” if preliminary clinical evidence suggests it has an advantage over existing options. Since then, there have been 76 FDA-designated “breakthroughs,” drugs that are often fast-tracked through the approval pipeline.

A few doctors are saying, “Not so fast!”  But they’re in the minority.  Most physicians tend to overestimate the efficacy of new drugs, according to a recent survey of 700 practicing physicians published in JAMA (April 12, 2016).

Dr. Aaron S. Kesselheim, lead author of the study, says this perception can result in over-prescribing a new drug and exposing patients to the risks inherent in a relatively unproven product. Doctors often assume that the FDA has reached its decision based on stronger evidence than is actually required from a legal standpoint.

As part of the survey, doctors were presented a hypothetical scenario in which they had to choose “between prescribing Axabex or Zykanta, both new, identical hypothetical drugs that met the criteria for breakthrough therapy, although only Axabex was labeled as such.  Overall, 94% of the doctors chose to prescribe Axabex (the breakthrough drug) while just 6% preferred the identical, non-breakthrough-designated Zykanka” (medscape.com).  In other words, the mere use of the term “breakthrough” was enough to sway the vast majority of doctors to prescribe “Axabex” even though it had no advantages over “Zykanta.”

“When people hear ‘breakthrough,’ it gives them an inappropriately elevated sense of what the drug might do,” says Dr. Kesselheim. “It may give physicians false reassurance about the outcomes they might expect to receive when they prescribe it.” The researchers noted that very few of the 76 “breakthroughs” have lived up to the promise behind the designation. “I wouldn’t be averse to calling true breakthroughs ‘breakthroughs,’ but that’s not currently what we’re doing,” says Dr. Kesselheim.

Most of the physicians surveyed believed the FDA approval meant that the newer drug had undergone head-to-head testing against other drugs used to treat the same condition. That’s not always the case. “It may be tested against a placebo,” says Dr. Kesselheim. “Just because a drug is approved doesn’t mean that it’s better or safer than other drugs out there.” (healthday.com, April 12, 2016).

Take the case of the heartburn medication Prilosec.  “When it came time for Prilosec to go generic, AstraZeneca marketed a new heartburn drug called Nexium for which it could still charge premium prices,” states Dr. Otis Brawley, CEO of the American Cancer Society. “They never said that Nexium simply contained the same active ingredient as their old drug Prilosec.”

Perhaps there should be a self-imposed, time-defined moratorium on the use of a new or “breakthrough” drug, especially when there’s a proven, efficacious, older drug that’s readily available.

When a new drug is first approved, it naturally carries more potential risk than a drug that’s been around for some time, because we know the least about the new drug’s safety until prescribed to thousands of patients over an extended period of time. Besides, a new drug will almost always cost a lot more than an older drug.

Ken Teufel, M.D., M.A.