(Bloomberg) -- Statisticians at the Food and Drug Administration who had a thorough look at the clinical-trial data didn’t support approval of Biogen Inc.’s Alzheimer’s therapy, internal documents released by the agency show.
The documents released on Tuesday show how top FDA officials weighed the concerns of their staff against the need of patients suffering from a serious fatal disease with no treatments that can halt its progression.
The drug, which will be sold under the brand name Aduhelm at a cost of $56,000 a year, was granted an accelerated approval on June 7. Such clearances come with the condition that a company conduct further study to confirm that a drug works as intended.
Biogen had conducted two big trials that yielded conflicting results. One found that high doses of the drug modestly slowed cognitive decline over 18 months. A second similar trial found no benefit in slowing decline.
Peter Stein, director of the FDA’s Office of New Drugs, said in a memo included in the released documents that the evidence on Aduhelm “is not sufficiently compelling or persuasive to meet the substantial evidence standard for standard approval.”
However, Stein said that trial results “strongly suggest that treatment with aducanumab may result in clinical benefit” and that an accelerated approval would be an appropriate way to bring the drug to market.
When drugs are approved through the accelerated pathway, “there is a recognition that there remains residual uncertainty of clinical benefit, typically because the studies assessing clinical benefit are ongoing, but here because the results of the studies assessing clinical benefit strongly suggested but did not establish benefit,” Stein said.
The clearance has since proven to be highly controversial. The FDA has faced criticism for approving the drug over the objections of its outside expert advisory committee, and three of the panelists have resigned. One, Aaron Kesselheim, a top Harvard doctor, called the decision “probably the worst drug approval decision in recent U.S. history.”
The agency has also come under fire from politicians, including West Virginia Senator Joe Manchin, who called for President Joe Biden to select a new permanent leader for the FDA to take the place of current Acting Commissioner Janet Woodcock.
According to a summary memo, high-ranking FDA officials including Patrizia Cavazzoni, director of the center for drug evaluation, Peter Marks, head of the FDA’s biologics center, and Rick Pazdur, an expert in the FDA’s use of accelerated approval, met on April 26 to discuss using an expedited clearance for Aduhelm.
Cavazzoni, Marks, Pazdur and others supported the move, while Sylvia Collins, director of the agency’s Office of Biostatistics, dissented, saying that “there is insufficient evidence to support accelerated approval or any other type of approval.”
A memo outlining the Office of Biostatistics dissent wasn’t posted Tuesday, though the office’s position was summarized by other officials who supported approval. The FDA typically posts review documents several weeks after a decision, but it put up the Aduhelm summary and the supportive documents early.
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In an interview on the day the drug was cleared, Biogen R&D head Alfred Sandrock said the company found out that the FDA was considering an accelerated approval in a meeting with regulators about a month before it was allowed onto the market. The company spent much of the time after that negotiating the drug’s label language, he said.
Top FDA officials were concerned about the effect on patients if they opted to order another trial to confirm Aduhelm’s benefits. If the agency had demanded a new study before approval, patients would suffer in the years it would take to complete the new trial, Stein wrote.
Such a delay could mean that patients eligible for treatment with the drug under an accelerated approval “could suffer irreversible loss of brain neurons and cognitive function and memory,” he said in the memo.
Aduhelm is expected to produce billions in revenue for Biogen, but there are growing concerns about the strain that its price, along with the cost of patient imaging and infusions, could put on the health-care system.
While Biogen shares surged when the approval was announced, the stock has since given back some of its gains, falling 10% since hitting a 52-week high on June 10.
On Monday, an employers group said in a letter to congressional leaders that the drug will end up costing taxpayers, the government and patients billions despite being unproven.
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