Conditional Approval for ‘Marginal’ New Drugs: Avorn

Harvard Medical School professor Jerry Avorn says the current FDA drug approval process under which a drug either gets full approval or is rejected should be changed. Writing in a Washington Post opinion piece, Avorn says that under the “pass-fail” system, a drug that FDA disapproves remains mostly unavailable, except to research study subjects, while a drug that is approved can generally be prescribed to anyone.

He cites the expected forthcoming full approval of Eisai/Biogen’s Alzheimer’s drug Leqembi (lecanemab) to illustrate the problem he sees. Avorn writes that in clinical trials the drug did not improve patients’ memory, but did slightly reduce their rate of cognitive decline, a small change that might be welcome to some patients, but unnoticeable to many others and their families. Because the drug had some clinical effect, however, he says, it is nearly impossible for FDA to disapprove.

He says the treatment requires intravenous infusions every two weeks, can cause cerebral swelling and bleeding, and will cost $26,500 a year, not including doctor charges. “How much minimal improvement in dementia is worth what level of patient burden and risk of complications,” Avorn asks.

His solution is to create a new status for some drugs that is neither full approval nor outright rejection, a conditional approval that would allow a new drug with “ambiguous credentials” to be used only in a limited way until better evidence is collected. “This would let doctors and patients learn how well it works in typical use outside of trials,” Avorn says.

The article concludes that medical science is not an all-or-none, once-and-for-all endeavor. “Knowledge evolves as evidence and experience accumulate,” Avorn writes, “and that’s wonderful. But FDA’s all-no or all-yes framework doesn’t fit the way our understanding of prescription drugs develops. For some drugs, the agency needs to become nonbinary to better reflect this reality.”