Part of our coverage of the 2019 Longevity Therapeutics summit. An index of all articles about the event appears here.
The morning session of the conference’s second day ended with a panel discussion devoted to several key questions and issues related to the development of anti-aging therapeutics:
How applicable to human aging is any given result in a model organism?
How to promote advances in biomarker discovery and validation in aging
Defining routes for translational success from discovery to clinic – what will be the
key factors for generating successful results?
Standardizing different classes of therapeutic approaches to achieve effective
Participants in the discussion were Anthony Oliva of Longeveron, Steven Braithwaite of Alkahest, and Ronald Kohanski of the NIA. Session chair John Lewis of Oisín Biotechnologies moderated. The text below is almost all paraphrased; direct quotes are indicated by quotation marks.
John: Are animal models capturing the complexity of disease? Are they suitable for testing new therapies:
Ron: When you model a disease, you make assumptions about what is causal, and these assumptions need to be tested rather than taken for granted. For example, mAbs recognize specific folded forms of a protein—but which conformation of each protein is responsible for the disease?
Anthony: Animal work is essential for safety. Efficacy information is great, but when you’re doing clinical work, the endpoint is regulatory approval.
John: What about biomarkers?
Ron: My understanding from my limited conversations with FDA that markers need to be causally associated with disease. I’m not sure what that means for agnostic approaches, and this is important given that aging is idiotypic.
Anthony: We really are blazing new tails here, so this is something FDA hasn’t previously worked with. Ultimately, the long-term objective of treating aging is about proving the long-term benefits. Did the patient’s healthspan improve?
Steven: We have to assess biomarkers, but we don’t know which ones yet. For some indications, you want to look at A-beta. They’re not regulatory endpoints yet, but they’re still important. In this field, we have a lot more discovery medicine ahead, so that we can start learning signatures, and begin to understand them. We’re still learning.
John: Thinking about the industry as a whole, what are the key barriers to inventing an anti-aging drug?
Anthony: You want to get regulatory approval on this stuff, and what we have to do is educate FDA about what that means, and work with them on surrogate endpoints that will enable us to get to market approval. In the future, if you want to get insurer reimbursement, you have to show cost-benefit.
Steven: The public perception is also difficult. “We’re curing aging” is not necessarily the message that should be put out now. Instead we’ll have impact on individual disorders, and collectively these approaches will evolve into anti-aging medicine.
Ron: If you decrease recurrent hospitalizations, it is beneficial—unless you happen to own the hospital. We’ll all need medical help as we get older. If you do have anti-aging therapies, that will improve public perception. As far as getting things through the FDA, that will involve some back-and-forth. As someone said, FDA isn’t interested in curing something that everyone has.
John: Let’s talk about the health economics of longevity extension, which isn’t often discussed.
Ron: We have three health economists in our division who are trying to understand what’s going on. I can’t really speak for them; it’s a black box to me.
Anthony: This analysis has to be done. If you want Medicare or other reimbursement, this has to be an integral part of that.