Lilly Delays Alzheimer’s Submission in Face of Proposed CMS Limitations

Eli Lilly_Cristina Arias_Getty Images

Cristina Arias_Getty Images

On January 12, the U.S. Centers for Medicare and Medicaid Services (CMS) released its draft national coverage decision regarding Biogen’s controversial Alzheimer’s drug Aduhelm (aducanumab). The primary bombshell of the draft guidance, which is currently open for public comment, is that the drug would only be covered in the context of a clinical trial. Many experts predicted that this would have negative downstream effects on other companies developing Alzheimer’s drugs, and now they seem to be correct.

As part of Eli Lilly’s fourth-quarter and full-year financial report, the company indicated that its timeline for an accelerated approval request for its own Alzheimer’s drug, donanemab, was no longer on schedule for the first quarter after the CMS draft guidance.

Dr. Dan Skovronsky, Lilly’s chief scientific and medical officer, in the conference call, said CMS’s ruling, “as currently written, essentially negates that patient benefit in Alzheimer’s disease. Still, we intend to complete our application for accelerated approval for donanemab yet this year, but we now move completion of the accelerated approval submission out of Q1.”

The rolling submission began in October 2021, and company executives hinted the company might wait for data from the Phase III Trailblazer 2 studies before completing the submission. That readout isn’t due until 2023.

For background, an accelerated approval is based on biomarker data in clinical trials. They typically require the biopharma company to then conduct after-market studies to prove clinical benefit. In the case of Biogen’s Aduhelm, the biomarkers were for clearance of beta-amyloid, an abnormal protein that accumulates in the brain of Alzheimer’s patients (along with another abnormal protein, tau). The drug definitely did so. What was less clear was if that clearance improved cognition. There was some data at the highest doses that the drug slowed cognitive decline, which is a significantly more complex and nuanced thing to prove.

In Lilly’s Trailblazer-Alz trial, donanemab decreased beta-amyloid levels on average by almost 80%. Although not a head-to-head trial — that’s in progress — it is suggestive of better beta-amyloid clearance than Aduhelm. Prior to the CMS ruling — which is not yet final — Lilly’s drug seemed almost certain for accelerated approval in the wake of the Aduhelm approval. But the company appears to be strongly suggesting the CMS reimbursement plan would significantly undercut any reason to push the program harder.

Otherwise, Lilly reported revenue for the quarter of $7.999 billion, an increase of 8% from the previous year’s fourth quarter, and full-year revenue of $28.318 billion, up 15% from $24.539 billion in 2020. Top products for the year included Trulicity, which brought in $6.471 billion, Humalog, bringing in $2.453 billion, COVID-19 antibodies, reporting $2.239 billion, Taltz, with $2.212 billion and Alimta, bringing in $2.061 billion.

Lilly CEO David A. Ricks said, “2021 was another outstanding year for Lilly as we delivered strong top and bottom-line growth and positive pivotal readouts for five important assets with the potential to launch in the next two years. As we move into 2022, we continue to build on this foundation and are determined to deliver on our long-term outlook to drive top-tier revenue growth, expand operating margins and innovate to develop and launch new medicines for patients that address significant unmet needs.”

In 2021, Dr. Skovronsky touted positive data on five drugs: tirzepatide, tenenumab, pirtobrutinib, mirikizumab and lebrikizumab, which Lilly believes may launch in the next two years. The company has also launched or submitted data for new indications for currently marketed drugs, including Verzenio and Jardiance.

He also pointed out that Lilly has other drugs besides donanemab that it is developing for Alzheimer’s disease. The company received breakthrough therapy designation for N3pG4, an amyloid lowering agent. It expects to begin pivotal trials by the end of this year. Lilly also launched a Phase II trial for an oglic/nacase inhibitor, an oral small molecule that targets tau.

He added, “We remain confident in the differentiation of donanemab and in our uniquely designed TRAILBLAZER-ALZ-2 study. And importantly, the long-term opportunity to help patients with donanemab remains unchanged.”

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