Patient Voice Not Part of CMS’ Decision on Alzheimer’s Drugs, Group Says

The Centers for Medicare and Medicaid Services’ decision about the way Medicare will cover Alzheimer’s drugs — only with traditional full approval and if patients participate in a registry trial — will set a precedent and limit patient access to other innovative medicines, according to a new paper by Patients Rising.

The nonprofit organization, which serves those living with chronic or rare illnesses, said this coverage decision will impact access to new cancer and rare disease drugs approved through the FDA accelerated approval program.

MacKay Jimeson

"Accelerated approval really happened because of the action of patients and patient communities. What we’re seeing now is that HHS and CMS is taking action for financial savings without listening to the patient's voice,” MacKay Jimeson, executive director at Patients Rising’s Patient Access & Affordability Project, said in an interview.

The accelerated approval process came out of patient advocacy during the HIV/AIDS epidemic of the 1980s, which saw activists protesting both at the FDA and pharmaceutical companies demanding earlier access to investigational medications. At the time, no medications were available to treat HIV or the opportunistic infection that resulted from AIDS.

The development and approval of zidovudine, also known as AZT, changed the way the agency viewed serious diseases. Zidovudine was approved in March 1987 without the manufacturer conducting a phase 3 study. The accelerated approval was based on a surrogate marker, in this case viral load.

Related: Accelerated Approval and the Tension Between Safety and Access

Since 1992 when the pathway began through June 30, 2023, the FDA has granted accelerated approval to more than 300 drugs. These drugs were approved based on surrogate markers, which are used to predict clinical benefit but don’t measure clinical benefit. Drugs approved through this process include many cancer drugs as well as gene therapies and first-in-class therapies for rare diseases.

“Accelerated approval is in statute, and Congress has made it a legitimate form of approval," Jimeson said.

CMS is focusing on cost cutting, he said. "Whereas CMS’ national coverage determinations (NCDs) are not developed by Congress. There may be changes that are needed, but I'd much rather have this conversation happening through Congress to determine the appropriate path of approval, rather than CMS arbitrarily deciding what is good and what is not a good surrogate endpoint.”

The accelerated approval in June 2021 of Biogen/Eisai’s Aduhelm (aducanumab) to treat patients with Alzheimer’s disease proved controversial due to mixed results from clinical trials and Biogen's pricing of the therapy, which the company eventually reduced by half. Now with the full approval Biogen/Eisai’s Leqembi (lecanemab-irmb) in July 2023 and Eli Lilly’s submission of full approval donanemab, which an expected decision at the end of the year, patient advocates are concerned access will be limited.

Jimeson predicts this CMS decision will have an impact beyond Alzheimer’s drugs. “There’s this questioning of surrogate endpoints and the accelerated pathway. That is a disservice to Alzheimer’s caregivers, the cancer community, and the HIV/AIDS community, which fought so hard to make this a reality.”

He pointed out that surrogate endpoints are not developed in a vacuum. “It's a conversation between the manufacturer and the regulators to determine what are appropriate measures to help get these drugs approved. There is some fair criticism as relates to surrogate endpoints. My bigger concern though, is the counter narrative that the surrogate endpoints aren’t necessarily valid measures.”

Additionally, Jimeson said CMS’ registry study is redundant and doesn’t factor the administrative burden that is being placed on physicians. “I’m unclear on whether this is just for Alzheimer’s medicines or other drugs going forward. Are they trying to have more control over the evidence that’s being generated? Or is this just simply not understanding how the process of evidence generation is being done today?”