Medicare Alzheimer’s Coverage Policy Advancing Clinical Trial Diversity Efforts

GAP President John Dwyer spoke with Cathy Kelly of Pink Sheet about the Bio-Hermes study, the necessity for diversity in #Alzheimers clinical trials, and how industry-sponsored trials are out pacing government-sponsored trials. 

Although Alzheimer’s stakeholders are dismayed by the treatment access restrictions imposed by the Medicare national coverage determination last spring, the policy has also jumpstarted improvements in clinical trials for Alzheimer’s drugs in an important way, according to Global Alzheimer’s Platform Foundation president John Dwyer. 

The Centers for Medicare and Medicaid Services cited a lack of diversity in the pivotal clinical studies on Biogen, Inc. and Eisai Co., Ltd.’s Aduhelm (aducanumab) as a key concern with the available data when it issued the decision that coverage will only be provided for Aduhelm and similar drugs in the context of a study, a policy known as coverage with evidence development (CED).  (Also see “Medicare Alzheimer’s Decision Varies Evidence Mandate For Accelerated vs. Traditional Approvals” – Pink Sheet, 7 Apr, 2022.)

GAP and advocacy groups including UsAgainstAlzheimer’s “were not enchanted by everything CMS did when it came to the Aduhelm decision and creating a class CED rather than a one-by-one NCD process. We were quite vocal about that,” Dwyer said with some understatement during a panel discussion at the recent National Alzheimer’s Summit hosted by UsAgaintAlzheimer’s.  (Also see “Medicare Alzheimer’s Drug Study Criteria Would Be Out Of Reach In Many States – Analysis” – Pink Sheet, 29 Mar, 2022.)

“But I want to go on the record here saying that what the [CMS] administrator did in standing up and saying, ‘Don’t come here with drugs that don’t look like the people you want to make it available to, the Medicare beneficiaries,’ was a good thing,” Dwyer said. “And it has changed everything.”  GAP is a non-profit dedicated to accelerating the development of innovative therapies for neurological disorders by reducing the duration and cost of clinical trials. 

As of last December, GAP “only had one study that had given us an absolute mandate with respect to finding a minimum population of underrepresented folks into a clinical trial. That was our own biomarker study,” Dwyer said. 

“Today we have five, and pharma has drunk the Kool-Aid. They still have a lot of work to do. But they have taken the steps … and they know that the game changed, that they’re being held accountable. And it is not going to be an easy conversation if they come in performing the way they did in the past. I think [the NCD] was a great contribution to creating momentum in the private sector to solving this problem.”

Studies That Are Succeeding With Diversity

The GAP biomarker trial, dubbed Bio-Hermes, is a platform study designed to compare results of blood and digital biomarker tests, including digital cognitive and voice assessments, with the results of brain amyloid PET scans and traditional cognitive tests.  

The study database will allow scientists to assess the ability of each biomarker, or combination of biomarkers, to prognosticate the accumulation of amyloid in the brain, which is believed to be a hallmark of Alzheimer’s. Partners in the effort include AbbVie Inc.Eli Lilly and CompanyMerck & Co., Inc. and the Alzheimer’s Drug Discovery Foundation.

GAP decided the Bio-Hermes study would not close until it had at least 20% African Americans and Latinos in the study. It concluded this month, with 24% diversity when including people who are of Asian and Native American descent, the organization reported 15 November. The total is significantly greater than the diversity of most Alzheimer’s disease clinical trials, which typically draw 3% to 6% of participants who are African American or Hispanic, GAP pointed out. Analysis of study results is expected in 2023.  

The group is involved in four other studies in Alzheimer’s that aim for at least 20% African American and Hispanic enrollment. One involves a partnership with Genentech, Inc. on a secondary prevention study for gantenerumab known as Skyline. The program uses strategies such as community engagement events, social media campaigns and outreach in primary care facilities as well as a site optimization program to encourage more diverse participation. 

“With Genentech, we’ve basically emptied the toolbox,” Dwyer said. “We’re going to try everything,” including strategies that “are not ubiquitously done in Alzheimer’s trials.” 

First, he said GAP hired more non-white trial recruiters because “if you’re going to go into communities and asking them to trust you, you better look and talk like you came from that community.” In training the recruiters, “we had to reach them to talk ‘pharma,’ rather than teaching pharma people to talk Latino or African American … So when they go back to the companies, they can tell the on-the-ground truth of what’s going on,” he explained.

Other approaches had to do with sites of outreach and care. “With the help of Genentech, we have our first mobile unit out in the field. It’s called THOR (taking health care on the road),” Dwyer announced. He noted the average clinical trial site is held accountable for four to six screens of under-represented population members for the average study. But “when we take THOR someplace, we’re doing 25 to 50 visits in one stop and we’re averaging 60% under-represented folks.”

The organization also started the first clinical trial site in the Rio Grande Valley in Texas for Alzheimer’s and other CNS conditions called Al Faro Health and Therapeutics, Dwyer said. The rationale is “if you want to recruit [diverse group of] patients … then go to a community where the only people you can recruit are African Americans or Mexican Americans,” he explained. Finally, Dwyer emphasized the importance of having Spanish speakers involved in recruitment so that “we don’t ask people to feel comfortable getting assessed in their non-native tongue.”

Unfortunately, gantenerumab’s Phase III GRADUATE program failed to demonstrate slowing clinical decline in people with early Alzheimer’s, so development of the candidate seems unlikely to continue.

The GAP projects are representative of what is going on more broadly in the field in terms of a diversity efforts, Dwyer explained in an interview. He acknowledged that some studies that were underway before the NCD was announced, such as Eisai Co., Ltd./Biogen, Inc.’s the Phase III CLARITY AD study on lecanemab, were already designed to include a diverse population. But he maintained the NCD has moved the needle further in other studies “extraordinarily quickly.” Approximately 27% of US enrollment in Clarity AD included Hispanics and African Americans with early Alzheimer’s disease, the companies reported last month.

“Due to the inclusive eligibility criteria and the successful recruitment of diverse ethnic and racial populations in the U.S., CLARITY AD’s population is generally comparable to the country’s Medicare population,” they said. Top line results from the study were announced 28 September.

Federal Policies On Diversity Tied To Grant Funding 

The National Institute on Aging has also taken steps to ensure that federally-funded research in Alzheimer’s includes a diverse patient population, Clinical Research Recruitment and Engagement senior advisor Holly Massett said during the meeting.

“We have just spent several months conducting extensive research with internal and external stakeholders to improve participation” in clinical trials and “are in the process of launching initiatives,” Massett said. “We heard loud and clear there is a need for more guidance on recruitment planning and also more resources for [Alzheimer’s disease] clinical trials to reach underrepresented populations.”

So “out of the gate, we’re ensuring that inclusive recruitment planning is included in all of our funding opportunity announcements and our funding of awards,” she said. “This is important because this language becomes part of the grantees’ terms and conditions of their award.” NIA is “also working to build off FDA 2022 guidance to ensure that we clearly define and provide justification for the plan enrollment,” she added.

NIA announced in June 2021 that investigators will be required, on a monthly basis, to electronically submit participant enrollment data into the NIA Clinical Research Operations and Management System (CROMS) for all subjects enrolled in their studies. CROMS will track, report, and manage extramural clinical research enrollment data, study documents, activities, and portfolios in real-time across NIA clinical research projects.

“What CROMS allows us to do is when a trial is activated in goes the enrollment planning by all of the inclusion criteria that NIH lists and we are able to track to make sure they are aiming to meet those. If they are not meeting those we can intervene early and help with this. It’s also making sure the planning out of the gate has the right numbers,” Massett pointed out.

She said NIA will publicly report on the progress of the trials in terms of inclusiveness, following a model for oncology trials established by the National Cancer Institute. But NIA does not plan to allow public access to the CROMS data. “It will be mostly used internally to manage the research portfolio,” she explained.

In terms of the progress on diversity being made in government-sponsored versus industry-sponsored trials, Dwyer maintained that “industry is outpacing government right now by an order of magnitude.” The “structure within academic sites to get the change we need is just going to be slow” because hiring is a much more cumbersome process, he pointed out. As a result, “industry is going to be way ahead of the government in the short term,” Dwyer predicted. “Longer term, I hope everybody raises all boats.”

Originally posted by Pink Sheet on November 21, 2022.

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