There have been a lot of news stories about pharmaceutical treatments for memory care disorders over the past few years. Understandably, healthcare leaders and patients are hoping for an effective treatment for Alzheimer's and other dementias.

We wanted to understand how likely this is. In this piece we examine the state of the memory care drug pipeline, to determine the likelihood of a paradigm-shifting pharmaceutical product hitting the market in the next five years.

We also explore what the effects of the pipeline analysis are for drug manufacturers in this space, and how they can leverage cross-stakeholder relationships to better position themselves for success in this difficult market.

Take-away #1: It is highly unlikely that, in the next five years, a breakthrough drug for memory care will emerge that will radically reshape the memory care landscape

Drug manufacturers have spent billions of dollars over the past three decades searching for a treatment that could effectively treat the progression of memory care diseases, but have yet to successfully identify one.

Manufacturers continue to pour large sums of money into this product line, so we examined what the likelihood is of a successful memory care treatment hitting the market in the next five years according to EvaluatePharma:

While there have been some promising reports emerging from the clinical trials of the two treatments hitting the market in 2023 that target the progression of Alzheimer's—Eisai/Biogen's Lecanemab and Eli Lilly's Donanemab—how well these therapies will work in the broader population remain to be seen. If neither of those therapies prove to be broadly effective—and history tells us that the odds are against them—the outlook for a transformative pharmacological intervention in memory care looks unlikely.

Only Anavex's Anavex 2-73 drug is given a better than 50% chance of making it to market in that timespan, so while it is certainly possible that a product could emerge from the life sciences that would reshape the memory care landscape, it appears unlikely that this will be the case in the near to mid-term.

Take-away #2: The creation of real-world evidence for drug effectiveness will become increasingly important for manufacturers of memory care drugs in order for them to land in payer and providers' formularies.

Although manufacturers have spent billions of dollars in search of "breakthrough" drugs for memory care patients, this decades long search has largely been a history of failures. Recent revelations that call into question the validity of the research which claimed to uncover the biomechanical source of Alzheimer's (the build-up of the protein amyloid beta in the brain)—on which most pharmaceutical development for Alzheimer's drugs is based—has only reenforced this narrative around the futility of memory care drug development.

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In 2021 Biogen brought their Alzheimer's drug Aduhelm to market but found few payers that were willing to cover it even after a 50% price reduction. The treatment successfully reduces amyloid beta protein build up in the brain for most patients, but stakeholders have remained unconvinced that it can produce consistently demonstrable outcomes across its indicated population.

This is in part due to new FDA oversight regulations, which have lowered the threshold for market approval so long as clinical trial evidentiary guidelines are followed. Moving forward, payers and providers are increasingly demanding evidence that drugs (especially high costs ones) will be effective from a clinical and cost perspective over time. This will require drug manufacturers to move beyond randomized clinical trials and invest in real-world evidence.

So, while the Aduhelm experience is the latest chapter in the longer narrative of challenges for the life sciences in this domain, it also marks a new direction in this story for the relationship between manufacturers and their purchasers.

In the face of the changes made by FDA, and the challenges Biogen faced convincing payers to cover Aduhelm, Eli Lilly is taking a mixed approach with their upcoming Alzheimer's drug, Donanemab. Eli Lilly has asked the FDA for accelerated approval in order to get their product enough market exposure to gather sufficient post-market, real world evidence to apply for full FDA approval down the road.

Eli Lilly's recognition that clinical trial data alone will likely not be enough to convince payers (particularly CMS), which have become skeptical of the efficacy of Alzheimer's drugs, to cover Donanemab illustrates how important it will be for manufacturers of memory care treatments to demonstrate real world outcomes for their products.

This increasing emphasis on real world evidence will require manufacturers to explore new, cross-stakeholder relationships with providers and Health IT organizations in order to quickly and efficiently gather data from the market.

Anne White, the head of Eli Lilly's neuroscience division, noted in a recent earnings call that Lilly plans to "build out the diagnostic ecosystem, to help physicians with the referral process and infusion systems" in the period between accelerated and full FDA approval, with the hope that "CMS would not continue to limit coverage for on-label treatments" after full approval.

We expect other manufacturers in the memory care space to follow this example and treat FDA approval process as another step toward gathering the kinds of real-world evidence necessary to convince skeptical payers to cover their treatments.

What pharmaceutical manufacturers need to do to overcome payer and provider reluctance in this space

1. Think creatively about collaborations with other stakeholders to quickly and efficiently gather post-launch, real world evidence of the effectiveness of their products.
   • Work with providers and medical device manufacturers to gather as many potential patients as possible, as quickly as possible, for their marketed products. Drug manufacturers will need to be careful not to run afoul of Anti-Kickback and Stark laws.
   • Leverage medical affairs leaders to engage these stakeholders in more transparent and far-reaching conversations about clinical trial findings that didn't make it into the FDA labelling discussion. This could provide specific guiderails for payer pharmacy directors to determine the proper indicated use for their products, with greater specificity, and expedite the drug's inclusion on payer formularies. While FDA has also recently relaxed regulations around manufacturer – purchaser communications, manufacturers will still need to be mindful of what kinds of conversations the guidelines described in FDAMA 114 allow for.
2. Conduct more targeted outreach to populations who are under-represented in clinical trials.
   • A 2017 FDA investigation revealed that only 48% of the clinical trial population include women (across all trials), while black participants comprised only 7% of the total clinical trial pool. With the increasing importance for manufacturers of real-world evidence in the memory care landscape, the demographics of clinical trial populations will need to align more closely with those of seniors in the general population who have these illnesses in order to better guarantee successful outcomes after launch. According to recent studies presented at the 2021 Alzheimer's Association annual conference, the biggest factors affecting clinical trial participation among underserved communities are lack of representation among those conducting clinical trial outreach and lack of childcare and transportation support.
   • Manufacturers should use the updated outreach resources provided by the National Institute on Aging to help guide their efforts toward a more demographically representative memory care clinical trial population.