It’s a depressingly familiar story in Alzheimer’s R&D: a lot of hype, sprinkles of hope, but then dashed when data day comes around.
We’ve seen it time and time again over the past 15 years from a particularly cruel disease that robs people of their memories and eventually kills them.
One of the main features of research in the sector has been the use of BACE inhibitors that are believed to slow down the buildup of sticky plaques of amyloid in the brain, which many see as a primary culprit of the disease.
But this research has so far failed to show a strong response in testing, with even the likes of Eli Lilly, Roche, Merck and Pfizer making no headway, although there is still some sentiment from analysts that Biogen’s aducanumab, which goes after the same target, can produce something other than failure.
Despite severely limited ROI in this area, some are still going after the disease, which affects around 44 million people around the world and thus remains a major unmet medical need, as well as a massive revenue potential if someone could get it right in testing.
Today, Novartis, Amgen and Banner Alzheimer’s Institute will begin collaborating on a major global prevention program called "Generation Study 2," using the BACE inhibitor CNP520.
The idea is that this drug can prevent or delay symptoms of Alzheimer’s disease (AD). The new trials will include people who are cognitively healthy but at genetic risk of developing AD by carrying either two copies of the apolipoprotein E (APOE) 4 gene (which is a risk factor for the disease), or one copy of the gene with evidence of elevated brain amyloid. Around one in four people carry a single copy of the APOE4 gene, but only about 2% of the world’s population carries two copies.
The three are already working on Generation Study 1 using the BACE inhibitor, but say this second test is bigger and aims to go for a broader, at-risk population, as GS1 is only testing on those with two copies of the gene. The programs are in phase 2/3.
GS2 started enrolling participants in the U.S. back in August but will eventually include more than 180 sites in more than 20 countries around the world (with 80 sites in the U.S.), and is aiming for 2,000 patients. These patients will be randomized to receive a dummy treatment or one of two doses (15 mg or the higher 50 mg) of CNP520, which has been co-developed by Novartis and Amgen.
“Expanding our collaboration with Banner Alzheimer’s Institute stands testament to our belief that preventing amyloid buildup is one of the most promising approaches to treating Alzheimer’s disease,” said Vas Narasimhan, M.D., CMO for Novartis and soon to be its new CEO. “If we determine that our BACE1 inhibitor can prevent or delay the onset of symptoms in healthy yet high-risk populations, this would represent a tremendous breakthrough for those that may face this debilitating disease.”
“This expanded collaboration builds upon the API Generation Study 1 which launched last year, and is another step in our effort to take clinical trials to a critical new stage,” added Pierre Tariot, M.D., co-director of API and director of BAI, a division of Banner Health, one of the largest nonprofit healthcare systems in the U.S. “This approach continues to shift the Alzheimer’s research paradigm from reversing disease damage to attacking its root cause before symptoms surface. It is our hope that by targeting people earlier, we will have a better chance of delaying or preventing the onset of the disease.”
In a webcast, Tariot, alongside Jessica Langbaum, Ph.D., principal scientist at the Banner Alzheimer's Institute; Ana Graf, M.D., global program head at Novartis; and Vissia Viglietta, M.D., Ph.D., executive director and global development leader at Amgen, spoke about the new GS2 program.
They were all confident, despite the string of setbacks for BACE drugs and the amyloid theory, that their programs could generate meaningful data, with Graf suggesting that dosing of these meds has been too low to show a real benefit.
When asked about what differentiates this medication from the rest of the class, Graf said: “The safety has really been key in the design of the molecule, and we think this is very important at this stage; I think the other important feature is that we need to intervene early.”
Tariot added that awareness around prevention research was also a major part of this program, and that he himself is a gene match participant: “I have chosen to do a cheek swab at home so that a research lab can know whether I am at a genetic risk [of Alzheimer’s] or not. Thousands of people around the U.S. are making that decision in their living rooms and kitchens, and it’s a pretty amazing phenomenon. We really want people to understand, not only how revolutionary these studies are, but also how revolutionary the outreach and recruitment efforts have been for this.”