CMS decision on Aduhelm is in, and it's bad news for Biogen

Biogen Hillerød, Denmark

The US Centres for Medicare and Medicaid Services (CMS) has firmed up its draft decision to limit reimbursement of Biogen's Alzheimer's disease therapy Aduhelm to a few thousand patients enrolled in clinical trials.

The final verdict from the CMS dashes any remaining hopes that Biogen may have held that it would be able to build a market for Aduhelm (aducanumab) in the six million people with Alzheimer's in the US, many of whom rely on Medicare to reimburse their therapies.

Aduhelm sales have been tiny since it was approved last year against the advice of an FDA expert committee, and with regulators in Europe and Japan reluctant to follow the US' lead and grant the drug marketing approval, that looks set to continue for the foreseeable future.

The CMS – which received more than 10,000 comments on the drug – said it had arrived at the National Coverage Determination (NCD) verdict because "questions still need to be answered" about Aduhelm and other drugs targeting amyloid in Alzheimer's treatment.

"We looked at the very unique circumstances around this class of treatments and made a decision that weighed the potential for patient benefit against the significance of serious unknown factors that could lead to harm," said CMS chief medical officer Dr Lee Fleisher.

The decision to limit prescribing of the drug to patients enrolled in CMS-approved trials affects not only Aduhelm but also other amyloid-targeting drugs in late-stage development, notably Biogen and Eisai's follow-up lecanemab, Roche's gantenerumab and Eli Lilly's donanemab.

Aduhelm was cleared under the FDA's accelerated approval process, based in no small part on the assumption that reducing amyloid in the brain can be used as a surrogate marker for cognitive benefit, similar to the way LDL cholesterol is used as a biomarker for cardiovascular disease benefit.

The pathway allows for a conditional approval, so a drug can be prescribed while additional clinical data is gathered, as occurred with Aduhelm. The amyloid hypothesis of Alzheimer's has failed to be backed up in numerous clinical trials, and CMS maintains that "no Alzheimer's drug of any type has succeeded, to date, in modifying disease progression."

Fleisher said in the CMS statement that the agency is prepared to provide "broad access" via Medicare "if a drug in this class shows evidence of clinical benefit through the traditional FDA approval process."

That suggest the accelerated pathway is closed to amyloid drugs, forcing all their developers to file a complete dossier to the FDA that is strong enough to secure full approval if they want to access the US market.

Biogen said that the CMS decision was "unprecedented" as the agency has broken with the usual approach of funding drugs that are approved by the FDA, noting that the distinction between accelerated and traditional approval "has never been applied to FDA-approved medicines for other disease areas."

The company has been under the cosh ever since CMS' draft decision, forced to cut staff in a bid to carve $500 million off its annual costs and facing investigations from the Federal Trade Commission (FTC), Securities and Exchange Commission (SEC) and federal government.

It has been trying to mobilise support for Aduhelm, with a campaign led by USAgainstAlzheimer's reportedly spending millions of dollars on advertising to lobby for freer access to the drug.

Other drugmakers, including Lilly, have gone on record saying they are uncomfortable with CMS effectively overruling an FDA approval decision. Both Lilly and Roche have said however that they will now use the traditional FDA review pathway for their drugs.

One crumb of comfort for Biogen is that the CMS will not require another randomised clinical trial that duplicates Biogen and Eisai's original studies, and could be in the form of a registry study. Either way, it could take years to generate the data needed.

Biogen has already been granted FDA approval for a phase 4 post-marketing trial, and is running two other studies on the drug, one an extension of one of its earlier studies and the other an observational trial.