Recent FDA approvals for disease-modifying Alzheimer’s drugs have lured entrepreneurs, investors and pharma companies back to the neurology space – but instead of me-too drugs, their interest has focused on new targets and technologies, according to a panel discussion at the 2024 Biofuture conference held at Cure.
The US Food and Drug Administration (FDA) has approved three drugs that aim to reduce amyloid beta plaque (Aß) in the brain, a marker of Alzheimer’s disease, including Aduhelm (aducanumab) in June 2021; Leqembi (lecanemab) in January 2023; and Kisunla (donanemab) in July 2024. While many debate whether Aß is the best target for Alzheimer’s, given years of clinical trials that failed to show a benefit to patients, the regulatory greenlight have spurred new interest in the space, said Karen Harris, MBA, CFO and Head of Mission-Related Investing at the Alzheimer’s Drug Discovery Foundation (ADDF).
“We have really never seen a more exciting time in Alzheimer's drug discovery,” said Harris. “We see pharma coming back into neurodegenerative disease, and I work with a lot of VCs, and we see them coming to us now and saying, ‘I want to see your portfolio of companies that are raising money.’ And I couldn't say that last year. So I really do think that there are some, I call them ‘neuro-curious VCs,’ out there, and I'm seeing really more interest than ever.”
Harris was speaking on a panel focused on "Neurodegenerative Disease Funding: Accelerating Scientific Breakthroughs," and joining were Joel Sandler, PhD, Associate Partner at Ipsos Advisory Healthcare; Christian Howell, CEO of Cognito Therapeutics; and Sean Lorenz, PhD, Senior Director of Product Solutions at Altoida.
Unlike the obesity space, which is subject to a research and investing frenzy around blockbuster drugs in the GLP-1 class, the neurodegenerative space is looking beyond therapies that focus on Aß, according to Howell.
“From an investor perspective, I think that there is some concern about the risk and the safety benefit for those,” Howell said. “But it has opened the door now, I think for alternative therapies.”
Some of these alternative approaches include devices – Howell’s company, Cognito, for instance, is testing a headset device that stimulates the brain with non-invasive audio and visual signals, which has shown in clinical trials to reduce functional decline and reduce memory loss in patients with Alzheimer’s. Other companies are exploring different biomarkers, as well as combinations of treatments and prevention approaches.
“It may not just be one drug you need to take, but rather, like in cancer, where there's combination therapy and prevention, and that maybe it's going to take a multitude of things,” Harris said.
The surprising result of this increased attention since the approval of the three monoclonal antibody treatments for Alzheimer’s, according to Howell, is the pivot investors have made to on what really matters – patients – as opposed to what mechanism of action (MOA) different therapies use.
“When the monoclonals were coming to market a year ago, a lot of our conversations were around MOA, and it feels like now a large portion of those discussions are being consumed by the patient impact and the likelihood of patient adoption, which I think is great,” Howell said. “I love that so much of the investor discussions are shifting to being much more about the patient.”
The shift toward prevention and early intervention faces several regulatory hurdles. For instance, companies developing technologies for mild cognitive impairment (MCI) – a potential precursor to Alzheimer's – face an uphill battle with regulators who don't currently classify it as a debilitating condition.
"The FDA currently does not consider MCI as a debilitating disease, and so this is actually a fight we have on the breakthrough device designation," Lorenz said. "Just because you're not showing symptoms doesn't necessarily mean it's not debilitating or will be down the road."
Another challenge comes from healthcare delivery systems, which are eager to move treatment out of clinical settings but need clear reimbursement pathways. Regulators like the FDA and Centers for Medicare and Medicaid Services (CMS) have begun addressing these concerns.
"The FDA and CMS have done a really nice job of providing some clarity for companies to share with investors," Howell said. "In a lot of our discussions with investors, when we get past the clinical and then there's questions about regulatory coverage and adoption, those organizations have leaned in to help us be able to provide a little clearer message to investors that there is a pathway forward."
The emergence of blood-based biomarkers and digital assessment tools could help overcome some of these barriers by making diagnosis cheaper and more accessible than current methods like PET scans. ADDF has committed $100 million to developing these diagnostic approaches, which Harris sees as inseparable from therapeutic development, Harris said.
"We're really excited about the blood-based biomarkers, which I think is going to lead to earlier detection, and it's much cheaper than the PET scan," Harris said. "You really can't have one without the other."
These newer approaches are finding increasing acceptance among both doctors and patients. According to Lorenz, about 80 percent of patients now say they would be willing to do cognitive tests at home – a dramatic increase from just 10 to 20 percent five years ago. This shift toward home-based care could help address another key challenge: getting treatments to patients outside major medical centers.
The emergence of multiple therapeutic approaches, combined with clearer regulatory pathways and increasing acceptance of home-based care, has created what many see as an inflection point for the field. While the first wave of amyloid-targeting drugs faced skepticism, they helped prove a path forward, Harris said.
"We really are where cancer was 20 years ago. And I feel like perhaps the investment community doesn't want to miss out, that they think they need to be involved as well," Harris said. "Now I know these anti-amyloid antibodies aren't the perfect solution, and they're a first-generation drug, but it's progress. We showed that we could get a disease modifying product through regulatory and through the clinic, and I think that that gives hope to many."