Press Release

June 24, 2021
1 min read

FDA grants two antibodies breakthrough therapy designation for Alzheimer’s disease


Press Release

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The FDA granted breakthrough therapy designation for two investigational antibody therapies in Alzheimer’s disease. Lecanemab is an anti-amyloid beta protofibril antibody and donanemab targets N3pG, a modified form of beta amyloid.

The FDA based the breakthrough therapy for lecanemab (BAN2401; Eisai/Biogen) on results from a phase 2b clinical trial comprising 856 patients with mild cognitive impairment due to AD and mild AD with definitive amyloid pathology. In the proof-of-concept Study 201, investigators examined the effect of lecanemab for decreasing amyloid beta in the brain as well as clinical decline. A prespecified analysis demonstrated a consistent decrease in clinical decline based on several clinical and biomarker endpoints at the highest dose of lecanemab, according to the press release from Eisai and Biogen, while open-label extension data from the trial confirmed a time-dependent decrease in levels of amyloid beta in the brain among patients newly treated with lecanemab.

Additional research on lecanemab is ongoing. In March 2021, the drug’s manufacturers finished enrolling 1,795 patients with early AD in the phase 3 Clarity AD study. That trial’s primary endpoint should be completed by the end of September 2022. Moreover, in the phase 3 AHEAD 3-45 study, researchers examined the use of lecanemab in patients with preclinical AD; these patients are clinically normal, but have intermediate or elevated levels of amyloid in the brain, according to the press release from Eisai and Biogen.

The agency based the donanemab decision on a phase 2 trial, TRAILBLAZER-ALZ, which examined the safety and efficacy of donanemab in patients with early symptomatic AD, according to a press release from Eli Lilly and Company. The trial included 272 patients who were enrolled based on cognitive evaluations as well as amyloid plaque imaging and tau staging according to PET imaging.

The change from baseline through 76 weeks in the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite tool combining the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog13) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) for function, served as the primary endpoint. Key secondary endpoints included changes from baseline through 76 weeks in the ADAS-Cog13, ADCS-iADL, Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores. Other secondary biomarker endpoints included changes from baseline to week 76 in brain amyloid and tau deposition and volumetric MRI, according to the Eli Lilly press release.

Earlier results from that trial, from March 2021, included 257 patients, with 131 assigned to the donanemab group and 126 to the placebo group. The researchers observed a change from baseline in the iADRS score at 76 weeks of 6.86 among patients receiving donanemab and 10.06 among patients receiving placebo (difference, 3.2; 95% CI, 0.12 to 6.27), with a smaller reduction representing less cognitive and functional decline, according to the study results. An analysis with a mixed model for reported measures (MMRM) showed that, at 76 weeks, the estimated percent change in the iADRS score in the donanemab group, compared with the placebo group, was similar to the Bayesian disease progression ratio over the entire 18-month period. According to this ratio, the posterior probability of at least 25% slower disease progression in the donanemab group than in the placebo group, as measured by the iADRS score, was calculated as 0.78.

Results regarding secondary outcomes were “mixed,” according to the researchers. They observed no significant difference in CDR-SB scores between the two groups, which prevented them from making “definite conclusions” about the differences in ADAS-Cog13 scores. The investigators saw no significant differences between the groups regarding ADCS-iADL and MMSE.

"The Alzheimer’s Association welcomes these FDA actions as exciting advances in the Alzheimer’s treatment pipeline. They underscore the scientific validity of pursuing this treatment pathway,” Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, said in a press release issued by the organization. “We know that history shows FDA action leads to greater investment and innovation, and the discovery and development of more and better drugs. This is already happening. While these new announcements are encouraging, we need to continue to diversify the Alzheimer’s treatment pipeline.”


Eisai Global. Eisai and Biogen Inc. announce U.S. FDA grants breakthrough therapy designation for lecanemab (BAN2401), an anti-amyloid beta protofibril antibody for the treatment of Alzheimer’s disease. Available at: Accessed June 24, 2021.

Lilly. Lilly's donanemab receives U.S. FDA's breakthrough therapy designation for treatment of Alzheimer's disease. Available at: Accessed June 24, 2021.