On June 7, FDA approved Aduhelm (aducanumab) to treat patients with Alzheimer’s disease using the Accelerated Approval pathway, under which the FDA approves a drug for a serious or life-threatening illness that may provide meaningful therapeutic benefit over existing treatments when the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients and there remains some uncertainty about the drug’s clinical benefit. Aduhelm is the first novel therapy approved for Alzheimer’s disease since 2003. The decision was made over the objections of a panel of outside experts.
Approval’s Impact on Other Drugs
Aduhelm was approved using the Accelerated Approval pathway. With billions in revenue in reach for Biogen, other companies are likely to ask whether they can also pursue accelerated approval. As reported, FDA seems to be encouraging companies to seek this kind of approval. Some may consider whether data from past failures might be mined to support renewed regulatory discussions, or at least reviewed again.
“I think maybe some prior failed products would be taken off the shelf and dusted off,” Caleb Alexander, a professor of epidemiology and medicine at the Johns Hopkins Bloomberg School of Public Health.
In fact, FDA’s drug center chief, Patrizia Cavazzoni told reporters she hopes the accelerated approval will be used more frequently for neurodegenerative diseases. However, this may not be possible in all cases, as a recent article points out ALS drugs have struggled to find similar approvals from FDA.
Who Will Pay?
The $56,000 annual price tag on the therapy is far higher than the $8,300 estimated by the Institute for Clinical Economic Review (ICER) to be cost-effective, setting the stage for potential insurance challenges. “Only a hypothetical drug that halts dementia entirely would merit this pricing level,” ICER said in a statement. “The evidence on aducanumab suggests that, at best, the drug is not nearly this effective.”
MedPage Today writes that insurers will weigh the value of the drug, as well as the accompanying scans, infusions, and other procedures, in any coverage decisions. The drug’s label recommends obtaining an MRI prior to initiating treatment, and obtaining MRIs “prior to the 7th and 12th infusions” to assess risk of ARIA-H, or cerebral microhemorrhages.
All eyes are on CMS given that a significant proportion of Alzheimer’s patients are covered under Medicare. The agency could launch a National Coverage Determination (NCD) process for aducanumab, according to a Health Affairs article by Sean Dickson, JD, MPH, of West Health Policy Center.
NCDs are “the most powerful coverage tool Medicare has,” Dickson and colleagues wrote, and they’re generally reserved for costly treatments, services that have variable local coverage decisions, or when there’s scientific dispute about efficacy in beneficiaries. Aducanumab meets all three of those criteria, the paper argued.
Medicare also has the option of issuing a “Coverage with Evidence Development” decision that would cover those enrolled in a clinical trial aimed at collecting more data, as was the case for amyloid PET imaging.
As for commercial insurers, Biogen and partner Eisai said in a press release they “intend to enter into a value-based contract” with Cigna “to ensure that there is a streamlined path to access treatment for patients consistent with the population in which Aduhelm was studied.”
Post-Approval Studies
As reported by STAT News, Biogen CEO Michel Vounatsos said that the company could take up to nine years to satisfy the FDA’s post-approval requirement that it conduct an entirely new clinical trial to confirm the benefit of the drug for patients with Alzheimer’s. STAT notes those remarks were not received well inside the agency because they suggested Biogen felt no urgency to complete the study in a timely manner.
STAT writes: “I don’t have a timeline, but we certainly hope to see the study completed in the next several years,” said the official, who asked not be identified in order to speak freely.
“I can tell you that we will certainly be looking to make this trial as efficient as possible, to make sure Biogen is putting as much resources into it and that the trial can be done as expeditiously as possible,” the official added.
In a letter issued by the FDA and sent to Biogen, the agency asked the company to be ready to start the study by August 2022. The study needs to be completed by August 2029 and a final study report delivered to FDA by October 2030. But the FDA official said the agency considers the nine-year timeline to be a “conservative estimate” and a “starting point” for the discussions between Biogen and the FDA about the design and conduct of the study.