Kineticos’ SVP of Biopharma, Kevin Hampton leads our panelists through a discussion on what is next in the Alzheimer drug development crusade.
- Aaron Burstein – SVP of Clinical Development, vTv Therapeutics
- Sharon Rosenzweig-Lipson – VP of R&D, AgeneBio
- Jay Mohr – CBO, AZTherapies
- Jason Kralic – Co-Founder and CEO, Tellus Therapeutics
Kineticos: What did we learn from Biogen’s Aducanumab trials before they shut it down in March? What other approaches out there are gaining speed and are they the genesis of learning from others?
JK: There have been approaches emerging that are congruent or different from the beta-amyloid hypothesis that are now gaining attention. Some of those include mechanisms treating the chronic unresolved neuroinflammation driving the neurodegeneration as well as the metabolic instability that occurs with aging as seen with programs from Bioscience Pharma Partners and T3D Therapeutics, respectively. I’m pleased to see that the focus has shifted away from the beta-amyloid hypothesis and is starting to support some other mechanisms that should have been tested long ago.
AB: The focus is on addressing the neuroinflammation and the doors that have been opened for people to pursue areas that perhaps couldn’t previously gain interest or funding to pursue. There are numerous different approaches that are being targeted, which opens up the opportunity for potential combination therapy should a number of us be successful. We have focused on our molecule’s target and mechanism of action, potentially impacting various aspects of Alzheimer’s disease such as abeta, phosphorlation of tau metabolic dysregulation and importantly inflammation, as essentially being a combination therapy with one medication.
JM: Our treatment is a combination. In part, we think it to be appropriate because the brain is a complex organ. One of the challenges with the beta-amyloid approach is it is very focused on one target, a single approach to address all these different angles. Treatments need to be safe enough to be given chronically and to be combined with other potential therapies.
SR: It’s important to give these other approaches the time to mature. I would be cautious of putting all our eggs in the next basket too soon, we need to figure out where they fit in. You may take one or more drugs with different mechanisms to see what combination works best. Having that array of different targets and approaches really is quite valuable. The risk, however, is whether the dollars will be available to take all of these approaches forward and have sufficient funding to allow for program maturity.
Kineticos: Is the FDA serving as an enabler with Alzheimer’s Disease as they have been in a lot of other areas in the recent years to push these new approaches?
SR: They’re going to be quite helpful and supportive as they’re trying to find ways forward. A lot of the work they did previously that identified earlier stages of disease has been very helpful; what profile, what kind of instruments, and what would be an acceptable pre-clinical pathway. They’ve done a good job of opening pathways, not closing them.
AB: There’s been some forward movement in regard to defining stages of disease where patients have dementia and endpoints that may be appropriate. The FDA seems to be more progressive in encouraging sponsors to go to them with new measures to assess cognition, especially those that may be more sensitive than the tools we currently have. At this time, the door has been opened for dialogue, but nobody has reached a point where they’ve had positive clinical trial data to really see how far the Agency will go in regard to accepting new endpoints for registration. Another question is perhaps the scenario where you have robust significant cognitive benefits and trends on functional endpoints that don’t achieve statistical significance.
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