When Biogen and its Big Pharma partner Eisai last month announced with more than a little fanfare that their new experimental drug had slowed cognitive decline among participants in a clinical trial, the reception was predictably mixed. You can count me among the skeptics.
Biogen, after all, is still licking its wounds after practitioners universally shunned its earlier Alzheimer’s drug, Aduhelm, and Medicare officials were so underwhelmed by its efficacy that the agency limited its coverage of the treatment to those participating in future clinical trials. Plus, the performance of the new drug, lecanemab, has raised similar questions about its ability to battle dementia. Trial participants taking the drug saw a mere .45-point improvement on an 18-point scale compared with a group taking a placebo.
“I wish I could be more impressed than I am at this point,” Stanford neurologist Victor Henderson, MD, tells STAT News. That half-point difference, he adds, is “probably too small to be noticed by patients and their families.”
And yet, despite the kerfuffle over Aduhelm and the tepid trial results of lecanemab, the Food and Drug Administration (FDA) will surely consider the new drug for accelerated approval. The reasons behind that sort of decision go way beyond the desperation of Alzheimer’s patients and their caregivers. It’s all about the money.
Back in the late 1980s, under extreme pressure from activists clamoring for new drugs to fight the AIDS epidemic, the FDA cut a deal with Big Pharma to expedite the reviewal process. The drug companies agreed to pay hefty “user fees” (currently around $3 million per application) to help fund the agency’s drug-approval process. Congress, which has seldom been interested in providing the agency with adequate funding, loved the idea and passed the Prescription Drug User Fee Act in 1992.
The gambit certainly paid off for those suffering from AIDS, as the accelerated review process brought drugs to the market much quicker than would’ve been possible under the old system. And those medications have turned the once-deadly disease into a manageable chronic condition. And, as former FDA official John Jenkins, MD, tells Arthur Allen in Kaiser Health News, it’s opened the lines of communication between the agency and the industry. Before the shift, he says, “It was pretty challenging to get a meeting with FDA.”
The [FDA] hosted more than 3,000 meetings with Big Pharma leaders in 2019. Those gatherings have helped the industry better understand just what it takes to grease the regulatory wheels — leading to a dramatic increase in accelerated approvals.
That’s no longer the case, Allen points out: The agency hosted more than 3,000 meetings with Big Pharma leaders in 2019. Those gatherings have helped the industry better understand just what it takes to grease the regulatory wheels — leading to a dramatic increase in accelerated approvals. Only four of the 59 novel drugs (6.8 percent) that gained FDA approval in 2018 reached the market via that expedited process; three years later, 14 of the 50 approvals (28 percent) were pushed through at warp speed.
Meanwhile, those user fees have become a financial lifeline for the FDA, accounting for nearly half of the agency’s $6.5 billion annual budget. The upside for patients, on the other hand, is rather more obscure.
The Aduhelm controversy has been well documented, but it’s only one of several drugs that have been hastily licensed in recent years despite questionable trial results. Issues arise because the FDA bases its accelerated approvals on so-called “surrogate markers” of effectiveness — signs that Aduhelm, for instance, was able to reduce amyloid plaque in the brain — rather than clear evidence that patients will benefit from its use.
And, as Aaron Mitchell, MD, an oncologist at Memorial Sloan Kettering Cancer Center, notes, that process has introduced a lot of ineffective — and very spendy — pharmaceuticals into the marketplace. “If you’ve got a game-changing drug that truly is going to make a difference, you don’t need surrogate markers to prove that. If it’s effective, patients will survive longer,” he argues. The result, he adds, is “a lot of marginally effective, not clinically meaningful, more expensive drugs on the market.”
Ocaliva won accelerated approval from the FDA in 2016 after clinical trials showed that it lowered levels of an enzyme that may contribute to a rare autoimmune disease called primary biliary cholangitis. A year’s worth of the medication costs about $100,000.
But to hear UCLA liver specialist Steven-Huy Han, MD, describe his patients’ experience with the drug, you’d have to wonder whether it’s really worth the exorbitant price. “I have no idea if the drug will make them better,” he tells Allen. “It could take 10, 20, or 30 years to know.”
The same could be said about the new ALS drug Relyvrio, which the FDA approved late last month despite insufficient evidence of its efficacy. “Given the serious and life-threatening nature of ALS and the substantial unmet need,” the agency explained, “this level of uncertainty is acceptable in this instance.” Relyvrio will cost $158,000 a year.
I suspect the FDA will employ the same logic when it considers sending lecanemab on a speedy path to Alzheimer’s sufferers. Whether any of those folks will be able to afford the drug without Medicare coverage is anyone’s guess, and whether the further trials required as part of the rapid approval process will support the FDA’s expected ruling remains a major question.
Or does it?
When the Prescription Drug User Fee Act came up for renewal earlier this year, Congressional leaders sparred over language in the final bill that would make it easier for the FDA to remove drugs granted accelerated approval from the market if future trials didn’t provide solid evidence of lasting patient benefits. Big Pharma complained, and the language was ultimately deleted.
The result, said Stephen Ubl, president of the Pharmaceutical Research and Manufacturers of America, was “a win for patients, biopharmaceutical innovation, and regulatory predictability.”
Not to mention a steady stream of cash for the FDA.