Eli Lilly & Co. has announced plans to run a head-to-head clinical trial of its Alzheimer’s drug, donanemab, against Aduhelm (aducanumab), the controversial Biogen Inc. Alzheimer’s drug. Meanwhile, Aduhelm has continued to have what one expert calls “the worst drug launch ever,” after state Medicaid leaders told CMS they want no part of paying for the drug.
In its third-quarter results, Biogen reported in a Securities and Exchange Commission filing that Aduhelm revenues totaled $300,000, citing the fact that many clinicians don’t want to prescribe the drug. Meanwhile, Eli Lilly & Co.’s donanemab is under an accelerated approval process. That process will include a Phase III study comparing donanemab directly to Aduhelm, according to Daniel Skovronsky, M.D., Ph.D., a Lilly senior vice president and its chief scientific and medical officer.
The firm will “conduct a head-to-head Phase III study comparing donanemab to aducanumab to assess superiority of brain amyloid plaque clearance in early symptomatic Alzheimer’s disease.…This study, TRAILBLAZER-ALZ 4, is expected to begin enrollment this year and we expect to share primary endpoint data in the second half of 2022,” Skovronsky said during Lilly’s third-quarter 2021 earnings conference call, according to a transcript prepared by the Motley Fool.
Accelerated Review Is Criticized
These setbacks are just the latest of many for Biogen. The FDA approved Aduhelm after an accelerated review, a move criticized by medical experts. Rumors of improper relationships between FDA staff and Biogen led the HHS Office of Inspector General (OIG) to investigate the approval. In August, state Medicaid heads sent a letter to CMS asking the agency to restrict use of the drug through a National Coverage Determination (NCD) and add the drug to the group of pharmaceuticals subject to restricted overage under the Medicaid Drug Rebate Program. As part of its NCD review, CMS could decide to ban Medicare reimbursement of the drug for some FDA-approved indications, according to press reports.
In short, widespread adoption of Aduhelm is less likely with each passing week. Indeed, its approval could be reversed by further review or the OIG investigation.
“This drug was approved by the accelerated approval process — the accelerated approval process is not full approval,” Ge Bai, Ph.D., tells AIS Health, a division of MMIT. Bai is a professor at Johns Hopkins University’s schools of public health and business. “So that does not mean this drug will be formally, fully approved. There [is] some subsequent review that [the FDA] has to do in the regular process. We have an understanding of the accelerated approval program — it’s always targeted on unmet medical needs. For this case [Alzheimer’s care], we have huge unmet medical needs — FDA is more likely to favor those places and give more slack. But that does not mean the drug will be fully approved.”
Jeff Myers doubts the FDA will reverse its approval decision, even though he thinks the drug shouldn’t have been approved. Myers is managing director and founder of RareRe Partners LLC and previously worked with Biogen in government relations.
Myers points out that serious safety concerns — the drug can cause brain bleeding in some patients — are the reason why further safety data can’t be collected. Some prominent physicians say the drug’s benefits don’t outweigh its risks. Their colleagues seem to have heard their concerns, so there won’t be enough patients treated with the drug to collect a meaningful statistical sample.
“The FDA is not going to pull the drug unless it gets new safety data,” Myers tells AIS Health. “And we already know, with $300,000 in sales, no one’s taking it. So the odds of picking up a serious safety signal are essentially zero — now that it’s in the market, nobody’s using it. They’re not picking up new safety data.”
Myers adds that the FDA is concerned with protecting its reputation, which has taken a hit due to various pandemic-derived controversies — and that whoever is nominated to be the permanent head of the agency will face harsh questioning from senators about Aduhelm and other accelerated approvals.
“For the agency, the best thing to do is just let that thing stick out there, so that hopefully they don’t have any more second guessing into why they approved the thing in the first place,” he explains. “The OIG just put out a report saying that Medicare paid $200 million-plus for accelerated drug approvals that didn’t actually work. You’ve got MACPAC [the Medicaid and CHIP Payment and Access Commission] out there saying that there should be greater discounts for drugs approved under accelerated approval. There’s all these questions around how this drug even got approved in the first place, and whether there was any hanky-panky. I have to believe that there’s going to be a lot of opportunities for members of Congress to want to know more about accelerated approvals.”
Myers, who has worked on many drug launch teams, says Aduhelm has been a disaster for Biogen: “I can honestly say that’s the worst launch ever.”
This story was reprinted from AIS Health’s biweekly publication RADAR on Drug Benefits.