I’m sad to say that we at Fierce Biotech did not predict that 2021 would be the year that Alzheimer’s disease drug development blew up. But I’m here to correct the record and make such a prediction for 2022.
This past year, the floodgates for new potential Alzheimer’s treatments were opened when the FDA approved Biogen’s Aduhelm based on biomarker data that suggests it could address an underlying cause of the disease—not on actual, proven clinical improvements. Executive after executive told us, and keep telling us, that this was a big deal.
And it was—even though it was highly controversial—but I’m here to tell you that 2022 is going to be even more interesting.
While Biogen got the FDA nod, Aduhelm's efficacy is still unclear and the drug has been on a “rollercoaster” since the approval, in the words of Stifel’s analysts. But with a new regulatory pathway opened up, many of the top pharmaceutical companies, including Eli Lilly and Roche, are powering up their development programs to follow suit.
That means we could soon start to see the fruits of the many studies that have been slogging along in the background for years. Many of the top therapies in contention—Lilly’s donanemab, Roche’s gantenerumab and Biogen/Eisai’s BAN2401 among them—will have some key data readouts in 2022 that could finally start to show whether we have a viable treatment option for patients with the debilitating neurodegenerative disorder.
Stifel said the big question for 2022 is how the amyloid hypothesis will evolve. Companies and researchers have been trying for years to show that the removal of beta amyloid plaques from the brain can alleviate Alzheimer’s. But the clinical record is littered with failures and mixed-bag data for every candidate tackling this target.
“Positive readouts will help validate a beta as a target and help bolster the case for Aduhelm, while negative readouts may further draw scrutiny to Aduhelm and the class,” Stifel wrote.
So Biogen could use the boost from donanemab and gantenerumab if they’re able to validate the beta theory.
Stifel is not sure gantenerumab will do that, however. The firm believes the drug has “the least compelling case” out of all the late-stage antibody candidates for Alzheimer’s. The forthcoming readouts in 2022 “seem risky,” according to the note. After a previous failure, Roche revamped the study protocol with a higher dose.
Biogen is working fast, too. The company was given nine years to complete a confirmatory study for Aduhelm, which was approved under the accelerated approval pathway, or face removal from the market. The company’s Chief Medical Officer Maha Radhakrishnan, M.D., told us in October that she is well aware that the pressure is on to show efficacy.
Just last week, Biogen revealed plans for that confirmatory study. The company and its partner Eisai intend to submit the final protocol for the phase 4 trial to the FDA for review by March and the first patient is expected to be screened in May. The ultimate enrollment goal for the placebo-controlled trial is 1,300 patients.
And then there are the launches. If Lilly does manage to seal an accelerated approval for donanemab, will the path to market be as messy? The company hopes not, and is doing plenty of planning to make sure its ducks are in a row, the drug’s launch leader Brandy Matthews told us in October.
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If Biogen and Eisai’s BAN2401 turns up strong data and ultimately gets authorized, Stifel said Biogen will have a chance at a launch re-do.
“It will be interesting to see how management frames this drug over time, and whether they view it as a chance to capitalize on learnings from their mistakes,” Stifel said.
With the controversial approval behind us, here’s hoping that 2022 will be the year that Alzheimer’s patients, their caregivers and doctors finally have a treatment that can truly help.