Johnson & Johnson has not been a name associated with the recent rush to find an effective Alzheimer's disease treatment. But the pharmaceutical unit of the largest healthcare company in the world has a two-pronged approach going on in the background that could someday give it a foothold.
The strategy includes pursuing precision medicines while at the same time working on biomarkers that can identify patients who will benefit most, and it recently helped attract a neuroscience veteran to Janssen Pharmaceuticals to drive the clinical program.
“That's the real sweet spot for where we're going to see breakthroughs,” says Fiona Elwood, Ph.D., disease area stronghold lead for neurodegeneration at Janssen. “That was really what attracted me to come join this team.”
Following more than 14 years in various neuroscience roles at Merck & Co. and then Novartis, Elwood moved to Janssen in January, where she heads up its various global teams seeking new therapies for neurodegenerative disorders. These include both a potential therapy and a vaccine for Alzheimer’s.
First, the therapy. The anti-tau antibody, dubbed JNJ-63733657, is in a phase 2 trial that launched in January 2021. The study’s aim is to demonstrate delayed cognitive and functional decline in participants with early Alzheimer’s disease who have evidence of elevated brain tau—proteins tangled inside neurons that have become central to the current crop of clinical therapies—as well as to assess the therapy’s safety and tolerability.
So far, antibodies targeting tau haven’t had the best track record. Big Pharma's pipelines are littered with trial failures, including Eli Lilly’s zagotenemab, Roche and AC Immune’s semorinemab, AbbVie’s ABBV-8E12 and Biogen’s gosuranemab. Biogen just axed a phase 1 tau-focused therapy called BIIB076, while focus shifts to another early-stage asset called BIIB080. Even with these competitors out of the way, it remains a crowded field, with Roche and UCB’s UCB0107 and Lilly’s ACI-3024 both in the clinic.
So where does Janssen’s candidate fit in?
“We really think this is differentiated,” Elwood said in an interview with Fierce Biotech. “The other assets are all targeting the N-terminus of tau, whereas we're targeting a disease specific epitope … that's right at the core, the business part of tau.”
After a positive early-stage trial, Elwood says Janssen is “really excited” for the potential of the therapy. But even if it clears phase 3, a shadow hangs over all Alzheimer’s therapies in the form of Aduhelm. Biogen’s therapy was the first ever to be approved for the degenerative condition but has faced controversies around the approval process, pricing and underwhelming sales.
While Elwood won’t comment on Aduhelm specifically, Janssen has clearly kept its eye on Biogen’s rocky road to approval.
“We look at all of the clinical data that gets generated by all of the companies who are running clinical trials in Alzheimer's disease,” she says. “Every piece of biomarker data or clinical data, the feasibility of running different trials—we learned so much from all of those. All of that goes into the design of our studies.”
Following the anti-tau antibody into the clinic is Janssen’s Alzheimer’s vaccine, dubbed VAC20121, which is the product of a partnership with AC Immune and currently in a phase 1b/2a study.
“We've seen good immunogenicity data,” says Elwood. “We're excited to see more data and the future for that particular asset.”
With a therapy and a vaccine, Janssen seems to have its bases covered when it comes to tackling Alzheimer’s. “There are different rationales for why we would advance two different assets,” Elwood explains.
The collaboration with AC Immune is representative of a pro-partnership approach to deepening Janssen's neuroscience pipeline.
“If you look at the whole of Janssen's pipeline, we have a strong history of partnering and working with both academic and biotech collaborators at all stages of discovery and development,” Elwood says.
With all the action in Alzheimer's from Biogen to Lilly to Roche and more—and with Janssen’s therapy still working through a midstage trial—it may seem like J&J is playing catch-up. But Elwood insists this is far from the truth.
“Obviously, Janssen is better known for psychiatric medications, but we've been working on Alzheimer's disease for over two decades,” she says. “There's been a history of us investing in significant clinical trials in this space.”
Finding the right patients
She points back to bapineuzumab, an intravenous treatment for Alzheimer's disease that was ultimately discontinued in 2012 due to a phase 3 failure. And alongside the ongoing search for effective molecules, there’s also Janssen’s work in identifying biomarkers for the disease.
“We firmly believe that with our strategy with precision medicine in Alzheimer's disease, we need to invest—and we have invested in—novel biomarkers as well,” Elwood says.
A study of one of these biomarkers, dubbed plasma p217+tau, has been shown to support diagnosis of the disease. The aim is to identify patients “very early” in the development of the neurodegenerative condition, “where that can predict the state of pathology in those patients’ brains,” she says.
So with a strong foothold in the Alzheimer’s space, what’s next for Elwood and her team?
“I think [Janssen’s global head of neuroscience] Bill Martin has been pretty clear on the strategy for neuroscience, that we're focused on precision medicine and bringing forward differentiated assets for diseases where there’s a large unmet medical need,” she says.
“That could be in broad diseases where you see diverse presentation and progression—like in Alzheimer's disease, for example,” Elwood adds. “Or it can be more focused rare diseases, where we have a clear genetic or biomarker way of characterizing those patients.”