Lilly Alzheimer’s BLA Rejected by FDA
FDA has issued Eli Lilly a complete response letter for its accelerated approval BLA submission for donanemab, indicated for treating early symptomatic Alzheimer’s disease. FDA’s rejection letter took issue with the “limited number of patients with at least 12 months of drug exposure data provided in the submission,” the company says, adding that no other deficiencies were cited.
In the letter, FDA specifically requested data from at least 100 patients who received a minimum of 12 months of continued treatment on donanemab, according to Lilly. “Donanemab’s specificity to target deposited amyloid plaque informed the unique clinical trial design of TRAILBLAZER-ALZ, which allowed patients to complete their course of treatment when they reached a predefined level of amyloid plaque clearance,” it explains. “While the trial included more than 100 patients treated with donanemab, due to the speed of plaque reduction, many patients were able to stop dosing as early as six months of treatment, resulting in fewer than 100 patients receiving 12 months of donanemab.”
Additionally, the agency said Lilly would likely need to include unblinded controlled safety data from an ongoing Phase 3 confirmatory trial (TRAILBLAZER-ALZ 2) when completed. A topline data read-out from the trial is expected in the second quarter, and the data will also form the basis of a traditional BLA submission shortly thereafter, the company says.
FDA review actions on Alzheimer’s drug submissions have drawn increased attention from Capitol Hill and other agency watchers following the 2021 controversial approval of Biogen’s Aduhelm (aducanumab). Late last month, a Congressional report on Aduhelm’s approval was sharply critical of the agency’s decision to work so closely with the company to guide the drug’s review and approval (see earlier story). The report found FDA’s interactions with Biogen were atypical and that the agency had deviated from its own guidance on documenting meetings with industry.
And earlier this month, Biogen/Eisai’s BLA for Leqembi (lecanemab-irmb) became the second expedited approval of a monoclonal antibody drug for treating Alzheimer’s (see earlier story). The approval documents included an uncharacteristic memo by CDER director Patrizia Cavazzoni that offered an explanation to FDA staff about the recent accelerated approvals. “While the approval of Aduhelm generated a significant amount of discussion among external stakeholders, CDER’s work during the review of the aducanumab application led to a leap in our understanding of amyloid as a surrogate marker and a greater understanding of the role that a reduction in amyloid plaque may play in a slowing of the disease,” she wrote in the memo.