Neurotrope Inc NTRP +10.38% Soon to be listed on the Nasdaq stock exchange, awaits Phase 2 results from its groundbreaking drug bryostatin, which actually seeks to reverse — rather than treat — the disease in late-stage patients by regenerating degraded synapses. Top-line data is expected in April.
Benzinga spoke with Neurotrope Chief Scientific Officer and President Dr. Daniel Alkon following Merck's trial suspension. Alkon was unequivocal in his response.
"Here's the punchline," Alkon said, "It's the same target - getting rid of amyloid. That target has been shown over and over again for 20 years not to be correlated with the causing of deficits. The only thing that's well correlated, clearly established, is the loss of the synaptic connections."
A study by professor Clive Holmes published in the Lancet supports the criticism of the amyloid hypothesis. Holmes found, during autopsies of dementia patients who'd undergone treatment for the removal of amyloid plaque, that while some had virtually complete plaque removal, seven of the eight still died with severe end-stage dementia. "In the whole cohort," Holmes wrote, "there was no evidence of improved survival or of an improvement in the time to severe dementia" versus the placebo group.
Accera has also criticized the amyloid hypothesis. In a press release titled, "Beyond the Failed Beta Amyloid Hypothesis" Accera's senior medical advisor Michael Gold said, "Now more than ever we need to focus on alternative mechanisms to address Alzheimer's disease." Accera seeks to address what it believes to be the fundamental metabolic defect in Alzheimer's patients.
Citing Lilly's failed trial and Merck's suspended trial, Alkon said, "There is a long line of trials, all going after amyloid in different ways, that never have worked. What we're trying to say is, look at the elephant in the room. The elephant in the room is look at the loss of wiring in the brain."
Is The Bar Set Too Low?
Something else you may have noticed: Virtually all clinical work in AD at present is performed on patients with only mild cognitive impairment and promodal AD. When asked what its recent trial news meant for the prevailing industry theory of AD treatment, Merck told Benzinga, "It is too early to speculate on what the EPOCH trial results mean for the validity of the amyloid hypothesis. It is hoped that by evaluating verubecestat in people at the earlier prodromal stage, who have lower levels of damage to the brain, we will be better able to slow disease progression."
In fact, Leerink analyst Geoffrey Porges in a research note suggested that the Merck suspension presented no added risk to the amyloid hypothesis but instead validated "the strategy of moving away from testing anti-amyloid drugs in moderate patients."
Alkon would disagree. "These trials are not working, and moving it up earlier and earlier is not going to change it," Alkon said. "Look at Biogen's trial. What people don't realize is that Biogen moved their trial so far up that there wasn't one Alzheimer's patient in the trial. They only looked at people who were mild cognitively impaired or confused. Only half of which go on to get Alzheimer's."
Neurotrope's bryostatin was developed through a focus on PKC epsilon - an enzyme which has been shown to be at a deficit in brains of AD patients. "It's not just restoring the synaptic networks, it's actually preventing the cascade of biochemical events whereby the neurons actually die. And PKC epsilon stimulated by bryostatin actually inhibits that, it prevents neuronal death and then in addition it stimulates synaptic growth. Those two things are unique."
So, why won't another, much larger company simply change focus from antibodies and BACE inhibitors to working with PKC epsilon? Well, in time one may do that, but to go to market with it is another story.
Neurotrope holds around 70 patents on its bryostatin and even more importantly, the rights to use PKC epsilon for treatment of AD. Alkon put it this way, "Suppose somebody else, let's say Lilly, came up with a new PKC epsilon activator, and let's say that it had good efficacy. The drug they came up with would be theirs, but to use it to treat Alzheimer's they'd have to work with us." And of the prospect of teaming up with pharma partners? "We'd be happy to work with them."
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