The Promise the Alzheimer Disease Pipeline Holds Heading Into 2022

Howard Fillit, MD, founding executive director, ADDF, provided his perspective on the state of the Alzheimer disease field as 2021 comes to a close.

This year has been a major year in the field of Alzheimer disease (AD), with several promising therapies moving forward and the first FDA approval in almost 2 decades. With the field experiencing a failure rate in clinical development of more than 90%,1 it has been a year of promise, particularly as this patient population consists of as many as 5.8 million Americans, according to CDC estimates, with the population’s size expected to triple by 2060.2

A number of reports on the state of the field have been published in recent weeks, including one that shows that the cumulative expense of private expenditures to fund AD clinical trials over the past quarter-century totals an estimated $42.5 billion, with the greatest costs incurring in late-stage drug development phases. This analysis, from Jeffrey Cummings, MD, ScD, professor of brain science, and director, Chambers-Grundy Center for Transformative Neuroscience, University of Nevada–Las Vegas, and colleagues, indicated that trial failures are common and that there has been a shift from research aimed at amyloid targets to that aimed more at diverse disease targets.1

Although, there is plenty of promise in the space despite these years of challenges. In recent months, rolling submissions were initiated for Biogen and Eisai’s second AD hopeful lecanemab as well as Eli Lilly’s investigational antibody donanemab,3,4 with the news that the FDA awarded Genentech/Roche’s gantenerumab with a breakthrough therapy designation occurring in the interim.5

Another report from the Alzheimer’s Drug Discovery Foundation (ADDF), based on a review of more than 200 clinical trials in AD, showed that in addition to the 118 disease-modifying treatments that are in the research pipeline, there are almost 100 more trials testing treatments that target behavioral symptoms of AD, such as anxiety and agitation; trials looking at ways to prevent AD from the beginning of its pathology; and trials validating new biomarkers that can be used to improve early detection and diagnosis.6,7

LISTEN NOW: Episode 53: A Landmark Year for Alzheimer Disease

To offer more insight into the development for Alzheimer disease, Howard Fillit, MD, founding executive director, ADDF, provided his perspective on the state of things to NeurologyLive®. According to Fillit, the most notable innovations of 2021 in Alzheimer disease include:

New Drugs

The approval of Aduhelm (aducanumab; Biogen), the first new disease-modifying Alzheimer drug in 17 years, set the path for 2 other antiamyloid drugs to receive potential accelerated approval in 2022. The approval of Aduhelm is significant not just because it is a new treatment option, but because it is the first time the FDA approved an Alzheimer drug based on a biomarker—in this case, a PET scan that showed the drug did what it was supposed to do (clear amyloid plaques from the brain). This approval shows biomarkers—disease signposts like plaques—are essential to designing and conducting effective clinical trials.

New Pathways

Research has shown us that conquering Alzheimer will require a combination of drugs that target the many underlying causes of disease, otherwise known as the biology of aging approach. This concept is already reflected in the diverse drug pipeline, where more than 3 in 4 drugs go beyond traditional amyloid and tau targets and instead explore novel targets.

Repurposed Drugs

More than 3 in 10 drugs in the Alzheimer pipeline are repurposed or repositioned, FDA-approved drugs that have potential for Alzheimer treatments. Intriguing possibilities include sildenafil (Viagra; Viatris), which according to a new study was associated with a 69% reduced risk of developing Alzheimer disease; and the diabetes drug semiglutide, which could slow the progression of Alzheimer by reducing inflammation and providing neuroprotection.

New Diagnostic Tools

The first blood test on the market to help diagnose Alzheimer, C2N Diagnostics’ PrecivityAD, is shown to be 81% accurate in predicting the level of amyloid in the brain and can now be ordered by physicians in 49 states. This blood test is also the first to be used as a screening tool in a clinical trial, paving the way for blood tests to play a larger role in both diagnosis and the development of new therapies.

Prevention

The best approach against fighting Alzheimer is to stop the disease before it begins. A growing body of evidence indicates people can potentially lower their risk for dementia through lifestyle modification in areas that include diet, exercise, and others. If we can delay the onset of Alzheimer disease by just 5 years, we can reduce the number of people with Alzheimer by about 50%.

Transcript edited for clarity.

REFERENCES
1. Cummings JL, Goldman DP, Simmons-Stern NR, Ponton E. The costs of developing treatments for Alzheimer disease: a retrospective exploration. Alzheimer Dement. Published online September 28, 2021. doi:10.1002/alz.12450
2. Matthews KA, Xu W, Gaglioti AH, et al. Racial and ethnic estimates of Alzheimer’s disease and related dementias in the United States (2015–2060) in adults aged ≥65 years. Alzheimer Dement. 2018;15(1):17-24. doi:10.1016/j.jalz.2018.06.3063
3. Eisai Initiates Rolling Submission to the U.S. FDA for Biologics License Application of Lecanemab (ban2401) For Early Alzheimer’s Disease Under the Accelerated Approval Pathway. Eisai. News release. September 28, 2021. Accessed December 17, 2021. https://eisai.mediaroom.com/2021-09-27-Eisai-Initiates-Rolling-Submission-To-The-U-S-FDA-For-Biologics-License-Application-Of-Lecanemab-BAN2401-For-Early-Alzheimers-Disease-Under-The-Accelerated-Approval-Pathway
4. Lilly reports robust third-quarter 2021 financial results as pipeline success strengthens future growth potential. News release. October 26, 2021. Accessed December 17, 2021. https://investor.lilly.com/news-releases/news-release-details/lilly-reports-robust-third-quarter-2021-financial-results
5. Ad hoc announcement pursuant to Art. 53 LR: Genentech’s anti-amyloid beta antibody gantenerumab granted FDA breakthrough therapy designation in Alzheimer disease. News release. Genentech. October 8, 2021. Accessed December 17, 2021. https://www.businesswire.com/news/home/20211008005371/en/Ad-hoc-announcement-pursuant-to-Art.-53-LR-Genentech%E2%80%99s-Anti-Amyloid-Beta-Antibody-Gantenerumab-Granted-FDA-Breakthrough-Therapy-Designation-in-Alzheimer%E2%80%99s-Disease
6. Alzheimer’s Drug Discovery Foundation releases 2021 clinical trials report in conjunction with 14th Annual CTAD Conference. ADDF. November 3, 2021. Accessed December 17, 2021. https://www.alzdiscovery.org/news-room/announcements/alzheimers-drug-discovery-foundation-releases-2021-clinical-trials-report-in-conjunction-with-14th-annual-ctad-conference
7. 2021 Alzheimer’s Clinical Trials Report. ADDF. November 2021. Accessed December 17, 2021. https://www.alzdiscovery.org/uploads/media/ADDF-CTR-2021-06-singles.pdf