Eli Lilly and Co. and Biogen Inc. are the leading players in an industry race to bring an Alzheimer's disease therapy to market first — and new promising clinical trial results from the Indianapolis-based pharmaceutical giant may have just upped the ante.
Lilly's donanemab helped slow decline in cognition and daily functions by 32% compared to placebo in patients with Alzheimer's, according to top-line results from a mid-stage study announced Jan. 11.
Alzheimer's disease has vexed major pharmaceutical companies with a trail of high profile failures — many of them Lilly's, the pharmaceutical company's CEO David Ricks acknowledged.
"We've been involved in running Alzheimer's studies for some time, as you know, a kind of rather dissatisfying exercise to this point," Ricks said in a presentation at the J.P. Morgan Healthcare Conference on Jan. 12. "Probably no entity has more experience in looking at failed Alzheimer's trials and tying to improve the framework by which we try to ascertain a benefit for these patients."
The company is seeking to reproduce the results of the latest donanemab study in a well-timed follow-up trial which will begin recruiting in the next couple of months, Ricks said. The results from that study could arrive as early as 2023.
"We made a bet I'm glad we made last summer by launching a replication study — we'll probably make a few tweaks to it based on what we saw here and call that a phase 3 or ... a second pivotal," Ricks said.
Meanwhile, competitor Biogen and development partner Eisai Co. Ltd. have experienced clinical and regulatory difficulties with aducanumab. The drug failed to impress an independent panel of experts reporting to the U.S. Food and Drug Administration, who voted against approval in November 2020. Research on aducanumab was halted in two trials early in 2019, but Biogen later revived the data, finding success in one of the trials later that year.
Biogen now awaits a March 7 decision by the FDA for final approval, which is seen as a crossroads for the company facing eroding sales of other core franchises.
"We are continuing to engage with the U.S. FDA as it completes its review, and we have continued to have very good regulatory interaction all around the world," Biogen CEO Michel Vounatsos said at the J.P. Morgan conference. "We are ready to launch in the U.S., and we are looking forward to the FDA final decision in the coming weeks."
There is still no approved disease-modifying treatment for Alzheimer's disease.
Another step for the amyloid hypothesis
Aducanumab and Lilly's donanemab both operate in similar ways by clearing amyloid plaque in the brain, thought to be a cause of Alzheimer's disease. Plaque clearing as a treatment for the disease is still considered theoretical.
"In our mind, we thought the amyloid hypothesis needed to be really tested — we thought this was going to be the study to test it because if plaques matter, then you need to get rid of them," Ricks said. "The sooner you do that, the better; the more robustly you do that, the better; and that's what donanemab does."
Analysts said Lilly's mid-stage results could lend more weight to the plaque theory.
"Though reported results are limited, today's [donenemab] top line is likely to reignite the bull debate on the amyloid hypothesis; however, we believe key differences between donanemab and aducanumab and questions remain," RBC Capital Markets analyst Brian Abrahams said in a Jan. 11 note. Abrahams predicted a less than 25% chance Biogen's drug would be approved by the FDA.
But analysts saw promise in Lilly's donanemab data, even though full details will not be released until the week of March 9.
Analysts Carter Gould and Justin Burns from Barclay's said in a Jan. 11 note that the 32% reduction in cognitive decline could give Lilly a leg up in the Alzheimer's market. The data could eventually mean Lilly has an asset capable of bringing in $10 billion in peak sales.
Other analysts want to see the full dataset before committing to donanemab as a successful Alzheimer's treatment.
"While it is great to have a successful trial in Alzheimer's disease, results are mixed," Cowen analyst Steve Scala said in a Jan. 11 note. "The effect size is small despite a tailor-made endpoint, and there were misses on some secondary endpoints, despite donanemab nearly completely wiping out plaques."
An apples to apples comparison between donanemab and aducanumab is difficult, according to analysts, because while they addressed similar types of patients in the existing studies, Lilly's was much smaller with 272 patients to Biogen's over 1,600.
"If aducanumab were approved due to FDA officials overriding the panel's decision, Lilly's asset would be a competitor, so we think it's important to focus on donanemab's own regulatory timelines and when they could enter the market," Cantor's Alethia Young said.
Biogen's Vounatsos said at the J.P. Morgan conference that the company does not have all its eggs in one basket with aducanumab; several Alzheimer's drugs are also on the docket for years to come. This includes BAN2401, another antibody with a similar mechanism to aducanumab that targets amyloid beta.
The J.P. Morgan Healthcare Conference brings together about 600 presenting companies and almost 13,000 attendees. The 39th annual conference in 2021 is being held virtually to curb the rate of infection of the COVID-19 virus.