Insufficient Evidence of Aducanumab Efficacy, ICER Draft Report Finds

A draft report from the Institute for Clinical and Economic Review, known as ICER, found that there is insufficient evidence to determine whether the investigational therapy aducanumab will provide health benefits to people with Alzheimer’s disease.

ICER is an independent non-profit research institute that works to assess the effectiveness and value of medicines and other medical services.

Notably, the institute’s Draft Evidence Report represents the midpoint of ICER’s assessment of the evidence on aducanumab — not a final decision.

Aducanumab, which is being co-developed by Biogen and Eisai, is an investigational therapy designed to break up toxic clumps of proteins in the brains of people with Alzheimer’s.

The therapy is being evaluated for potential approval in the U.S., with a decision expected by June 7. Regulators in Europe and Japan also are reviewing applications for approval.

To test the medicine’s safety and effectiveness in Alzheimer’s, Biogen had launched two Phase 3 clinical trials, ENGAGE (NCT02477800) and EMERGE (NCT02484547). After an independent advisory committee assessed interim data from these studies and determined that aducanumab treatment was unlikely to benefit patients, Biogen had decided in 2019 to stop developing aducanumab.

However, a later analysis that included more data indicated that, contrary to the interim analysis, one of the trials — EMERGE — had achieved its main goal. Specifically, relative to a placebo, treatment with aducanumab improved cognition and function, including memory, orientation, language, and daily living activities. ENGAGE did not meet its primary endpoints, though benefits were seen in some subsets of patients given high doses of the therapy.

These signs of efficacy have sparked hope in some, since currently, no therapy has ever proven effective for treating Alzheimer’s. According to David Rind, MD, the chief medical officer at ICER, a therapy that can effectively cure or prevent the progression of Alzheimer’s would be highly valuable.

“However, the clinical trial history and evidence regarding aducanumab are complex, and we believe that at the current time the evidence remains insufficient to determine whether the drug provides an overall health benefit,” Rind said in a press release.

“This is an area of tremendous unmet need, but this treatment has important side effects, and its wide use would have important ramifications for patients and health care budgets, making it all the more important that we know whether a therapy like aducanumab is, or is not, effective,” he said.

In its report, ICER conducted several analyses to examine the cost-effectiveness of aducanumab. The goal was to determine if the medication is likely to provide enough health-related benefits to patients to be worth the cost of treatment.

Results using data from both EMERGE and ENGAGE indicated that the medication might be cost-effective at prices of about $2,500-$8,300 per year — although the report stresses that these estimates are necessarily uncertain, since the data on the therapy’s effectiveness is unclear.

In other analyses that only included data from the positive EMERGE trial, a price between $11,100-$23,100 per year was calculated as likely cost-effective.

ICER’s Draft Evidence Report and Draft Voting Questions are open to public comment until June 2. Formatting instructions for formal comments are available on ICER’s website; the comments can be emailed to [email protected].

All comments will be reviewed by ICER, which will then make any warranted changes to the report. A final version of the report is expected around the end of June.

That report will be discussed during a virtual public meeting of the California Technology Assessment Forum (CTAF) on July 15. Registration for that meeting is available online, and requests to make an oral comment at the meeting can be submitted to [email protected].

Biogen recently launched an open-label clinical trial called EMBARK (NCT04241068) to continue testing aducanumab in people who had been in EMERGE, ENGAGE, or other clinical trials when development of the medication was discontinued.