Eli Lilly CEO David Ricks seemed to express a shrug over the FDA rejection of the accelerated review for Alzheimer’s med donanemab, while the company’s chief scientist batted back concerns that the agency was worried about safety.
The comments came during Lilly’s fourth-quarter earnings call Thursday. The Indianapolis pharma received a complete response letter from the FDA in January rejecting the application for donanemab and requesting more data from patients who had received the therapy for at least 12 months.
As analysts pressed for additional details about what the FDA is worried about, Lilly’s execs were clear that safety was not in question. One specific concern among analysts is a known complication in the treatment class called amyloid-related imaging abnormalities, or ARIA, which are abnormalities that show up in MRI imaging and can signal bleeding in the brain or swelling. Chief competitor Eisai has been dogged by ARIA issues for its latest Alzheimer’s offering lecanemab, which has beaten donanemab to the market via an accelerated approval granted in early January.
Chief Scientific and Medical Officer Daniel Skovronsky, M.D., Ph.D., was clear: the FDA did not flag any concerns about ARIA and the company essentially copy-pasted what the agency said in public communications about the rejection.
“I think that the FDA regulations actually suggest that FDA should list all deficiencies in the CRL. We were pretty explicit, copying some of the FDA's own words here to investors about what was in the CRL,” he said. “It didn't discuss issues like ARIA, it was focused on the 12-month exposure, so nothing further to speculate there.”
As for whether ARIA is a concern with donanemab, Skovronsky said that the data already collected suggest that the therapy’s rates are “very similar” to others in the class.
“My level of concern over that is not high,” he said.
Ricks said that even if the accelerated approval had been granted, Lilly was not expecting a lot of scripts to be written until Lilly secures a full, traditional approval. He cited the Centers for Medicare & Medicaid Services’ coverage determination that restricts coverage of new monoclonal antibodies for Alzheimer’s to patients in an approved clinical trial. The determination was issued for Biogen and Eisai’s Aduhelm and applied to all future medicines in the class that are granted accelerated approval.
Lilly has been one of the companies most vocal in pressing the agency to rethink the restrictions, but so far, the unlikely group of Big Pharma allies has been unsuccessful.
“We had hoped that there would be more movement from CMS to provide access to these medicines for people with Alzheimer's disease. Unfortunately, this has not yet materialized,” Ricks said.
The CEO pledged to work with the FDA “to evaluate the best pathway to make this potential treatment option available to patients.” Lilly plans to submit an application for traditional approval if the results from the TRAILBLAZER-ALZ 2 study are positive. The company—and the rest of the industry and investors—is eagerly anticipating these results, which are due in the second quarter.
Ricks believes that the devastating nature of Alzheimer’s, the unmet need and positive data will be enough to secure global reimbursement once a full marketing request is submitted.
Skovronsky said that the upcoming study will provide the 12-month data the FDA is looking for. Patients in the earlier TRAILBLAZER-ALZ study, which formed the basis of Lilly’s accelerated review filing, were allowed to stop treatment after reaching a pre-defined level of plaque clearance. “Due to the speed of plaque reduction that we saw,” many patients did not make it to 12 months, Skovronsky explained.
Lilly executives had previously planned to use the time in between accelerated approval and full market approval to educate physicians and prepare the healthcare system for donanemab. Lilly Neuroscience Executive Vice President and President Anne White said without the FDA’s blessing for early access, the company is still rolling on with that work.
“Obviously, accelerated approval would have made it maybe a little bit easier to do some of the things that we wanted to do, but there's still a great deal that we can do—actually have been doing—to make sure that the healthcare system is ready for these medicines,” White said.
Some of that work includes developing a diagnostic network to ensure patients can be identified and eventually treated.