Aduhelm: Catalyst for a Sentiment Shift

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At the 2022 Biotech Showcase several leaders in the field of neurodegenerative therapies came together to discuss relevant trends.  A notable shift has emerged since the approval of Aduhelm eight months ago that has led to a resurgence of interest and investment in Alzheimer’s Disease (AD).  In response, six industry experts gathered to contribute to a panel entitled Aduhelm: Stimulating the Next Generation of AD Treatment.  Moderated by Zacks’ John Vandermosten, the panel included:

1. Phyllis Barkman Ferrell, Eli Lilly;

2. Travis Bond, Altoida;

3. Michael McFadden, Alpha Cognition;

4. Lisa Ricciardi, Cognition Therapeutics;

5. Brent Vaughan, Cognito Therapeutics;

6. Eugene Williams, ProMIS Neurosciences.

Some History

During the mid to late 2010s, there was a slow but accelerating exodus from investment in neurodegenerative programs, especially in AD.  Perhaps it was the natural response on the difficult road to success, since the space was often perceived as a graveyard of failed programs and there had been no new drugs approved since memantine in 2003.  A lengthy list of challengers were jettisoned after missing endpoints or raising unacceptable safety issues in late stage trials.  

Investor interest in neurodegenerative disease, especially AD, had reached a nadir by 2019 and expectations were low.  When Biogen announced that it would halt its aducanumab trials, many were not surprised.  What little interest had remained in pursuing AD had further faded and many smaller companies developing AD programs de-emphasized or delayed them.  However, over the next two years Aduhelm would go on to experience a wild roller coaster of ups and downs which eventually resulted in approval and a new hope for AD drug development.  

Laboratory

New Financings

Following the Aduhelm approval, several transactions took place in the Alzheimer’s space.  Initial public offerings were completed for Acumen Pharma (ABOS), Alzamend Neuro (ALZN), Cognition Therapeutics (CGTX) and just recently Vigil Neurosciences (VIGL).  Additional equity investments were also made following the landmark approval, including companies represented on our panel: ProMIS Neurosciences and Alpha Cognition.  

Panel Themes

Several themes arose during our panel discussion including the importance of biomarkers, recognizing AD as a multifactorial disease and the benefit (or curse?) of being in the vanguard. 

Biomarkers

Biomarkers may be one of the most important tools to efficiently identify therapies that work - saving time, money and patient lives.  The FDA’s position on biomarkers has evolved as described in a 2018 update.  The most notable element provided in the document was the acceptability of biomarkers for determining efficacy.  

Biomarkers are especially important in earlier stage trials for their signal as to whether or not a drug is working.  If the drug is effective, the trial will continue; if no sign of benefit, the trial can be cut short and resources allocated elsewhere.  

Multifactorial Disease

AD has many causes.  Some of the best recognized include amyloid beta, tau, ubiquitin, protein misfolding, inflammation and oxidative stress.  Since there are many contributing factors, it appears that a variety of therapies will be needed.  There are at least five subgroups of AD that have been identified and each may need to be treated in its own way.  

Are First in Class Drugs Blockbusters?

Sovaldi, Lipitor and Humira were the top drugs of their class, however, they were not the first to be approved.  In 1998, lamivudine was the first anti-viral drug to be approved for hepatitis B, however, it was not until Sovaldi in 2013 that the most dominant anti-viral drug was available.  By 2014, Sovaldi generated $10.3 billion in sales.  The same phenomena occurred in statins.  Zocor was approved and generated first sales in 1988, but the greatest success in the class turned out to be Lipitor, which was the fourth drug available.  First sales for Lipitor did not occur until 1997, eventually achieving sales of almost $13 billion by 2006.  We also saw a follow-on product take the lead in the anti-TNF space when Remicade was launched in 1998 to modest success.  In 2011 Humira exploded on the scene in the US with almost $8 billion in sales, twice Remicade levels.  

These examples show that the best in class may not be the first and perhaps we shouldn’t worry that Aduhelm is not a panacea.  Several candidates in development, including Lilly’s donanemab, Alpha Cognition’s Alpha-1062, Cognition Therapeutics’ CT1812, Cognito’s GammaSense or ProMIS’ PMN-310 might just be that fast follower blockbuster.

Summary

Following years of neglect, investors have returned their attention to the neurodegenerative space.  While Aduhelm’s approval was a motivation, other factors are also responsible: supportive data from ongoing trials and the emergence of regulatory feasibility.  While the approval was imperfect, it does show the FDA’s willingness to step up when there is an extreme unmet need.  Our panel reflected on related themes including the expanded use of biomarkers, recognition that AD is a multifactorial disease and that first in class is not necessarily best.  We are eager to see what the next years bring!

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This post contains sponsored advertising content. This content is for informational purposes only and not intended to be investing advice.