BIIB: Final CMS Decision - Clinical Trials Only

UPDATED: CMS finalizes restrictions on Biogen's Alzheimer's drug coverage, will only fund use in clinical trials
Zachary Brennan
Senior Editor

CMS late Thursday finalized its decision to restrict coverage for Biogen’s controversial Alzheimer’s drug Aduhelm and other amyloid-targeted drugs to just patients participating in clinical trials.

“Monoclonal antibodies directed against amyloid that are approved by FDA for the treatment of AD [Alzheimer’s disease] based upon evidence of efficacy from a change in a surrogate endpoint (e.g., amyloid reduction) considered as reasonably likely to predict clinical benefit may be covered in a randomized controlled trial conducted under an investigational new drug (IND) application,” CMS said in its final decision summary.

While recognizing the rarity of this decision, in that it’s requiring a randomized controlled trial, CMS said it has finalized past National Coverage Determinations for drugs/biologics with CED but never with an RCT.

And it stressed that despite the FDA’s accelerated approval for Aduhelm, “currently no Alzheimer’s drug of any type has succeeded, to date, in modifying disease progression. No trial involving any intervention, alone or combined, has yet demonstrated a meaningful improvement in health outcomes for patients treated with anti-amyloid mAbs for the treatment of AD.”

The decision comes as Roche and Eli Lilly (CMS called the Phase II trial of donanemab “promising”) are also advancing their own amyloid-targeted drugs through late-stage trials, with readouts expected later this year, and high hopes, at least for Lilly, for a similar accelerated approval. Meanwhile, the decision from CMS also shows the limits of a fervent push among industry-backed Alzheimer’s advocates on Capitol Hill to reverse CMS’ earlier draft decision that laid out these coverage constraints.

CMS received over 10,000 comments on that draft, explaining on Thursday that, “None of the comments included new evidence that met our inclusion/exclusion criteria. However, Biogen’s recent publication of its EMERGE and ENGAGE trial results was reviewed as well as the new American Academy of Neurology (AAN) guidelines.”

In response to the “majority of public comments” saying “that there is not enough evidence showing that these drugs/biologicals provide a clinical benefit in order to cover anti-amyloid mAbs,” CMS said it “believes that the CED as modified in this final decision is the right balance of providing appropriate patient access and patient protections as well as generating evidence needed for patients, clinicians and caregivers.”

Part of that modification means that CMS will not require a separate randomized controlled trial that duplicates an RCT conducted for the FDA’s accelerated approval, and which Biogen already agreed on a protocol for.

“We removed the ‘CMS-approved trial’ language to further avoid any confusion with regard to CMS’ intent to support FDA required RCTs,” the agency says. But the final NCD also goes a step further and says that at this time,

CMS believes an FDA determination of a drug/biologic that demonstrates efficacy from a direct measure of clinical benefit would be promising but would not meet the 1862(a)(1)(A) reasonable and necessary statute. A prospective comparative study, which could range from a registry with a comparator to a pragmatic clinical study is appropriate coverage until CMS knows that the drug/biologic will demonstrate the same health outcomes, with reasonable risk of harm in broad community practice.

SVB Leerink analysts explained in an investor note Thursday how for mAbs that get traditional approval (which Roche is going for) based on direct measurements of clinical benefit, “CMS would provide enhanced access and coverage in CMS-approved prospective comparative studies, such as a data collection through routine clinical practice or registries. And these products could be covered in additional care settings, such as an outpatient department or an infusion center.”

The decision caps a tumultuous run for Biogen that began with an unexpected accelerated approval and expectations for tens of billions in sales, but ended with a fight over this CMS decision, significant layoffs and now limited coverage from CMS likely leading to continued anemic Aduhelm sales, potentially until the company can complete its confirmatory trial in about four years.

“Medical innovation must include clinical trials that demonstrate benefit to patients,” CMS said in its decision memo. “Conversely, covering a drug that has not been shown to be effective may incentivize production, marketing and sales of similarly ineffective drugs, at the cost of hard research to find ones that do provide a clinical benefit to patients.”

Biogen said in a statement:

These coverage restrictions, including the distinction between accelerated approval and traditional approval, have never been applied to FDA-approved medicines for other disease areas….Biogen is carefully considering its options and will provide updates as the company further evaluates the business impact of this decision.