Lilly's Donanemab Receives Unanimous FDA Advisory Committee Support with 11:0 Vote Affirming Benefit-Risk Profile for Early Symptomatic Alzheimer’s Disease

Jun 11, 2024 07:24 CST Updated 07:24

Eli Lilly

Global Pharmaceutical R&D and Production Company

June 10, FDAPeripheral and Central Nervous System Drugs Advisory Committee (PCNS)As forDonanemabFor the treatment of early symptomatic Alzheimer's disease（AD）The results of the meeting on the Biologics License Application (BLA) have been announced. The committee unanimously supported the drug's efficacy with an 11:0 vote and agreed that its benefits outweigh the risks.

Donanemab is a new generation product developed by Eli Lilly and CompanyAβ monoclonal antibody,Can bind to the β-amyloid subtype N3pG, thereby promoting the clearance of amyloid plaques in the patient's brain.

Source:PCNS ConferenceEli Lilly PPT

Eli Lilly had submitted the drug's marketing application in October 2021 based on data from the Phase II TRAILBLAZER-ALZ study, but the application was rejected by the FDA in January 2023. Four months later, after successfully completing Phase III...After the TRAILBLAZER-ALZ 2 study, Eli Lilly and Company submitted again to the FDAThe marketing application for Donanemab. The FDA was expected to review it in the first quarter of this year.The application was approved, but it was decided to hold a committee meeting for discussion.Several key issues with Donanemab have delayed the approval process.

▌TRAILBLAZER-ALZ 2 StudyTherapyEffective Data

Specifically, in the overall population (n=1736), compared with the placebo group, the ADAS-Cog scores of patients in the Donanemab group(iADRS, assesses patients' cognitive abilities and self-care capabilities)Scoring and Clinical Dementia Rating Scale(CDR-SB, assesses the patient's cognitive ability)The rate of score decline slowed down respectively.22%And29%。

Source: PCNS Conference Eli Lilly PPT

InMain analysis population (Low/Medium tau protein levels,n=1182),iADRS scores of patients in the Donanemab group andCDR-SB ScoreThe rate of decline slowed down respectively.35%And36%; andNearly half of the subjects (47%) No disease progression within 1 year(Defined as no decline in CDR-SB score), while the proportion in the placebo group was 29%.

Source: PCNS Conference Eli Lilly PPT

Moreover, Donanemab reduced the risk of patients progressing to the next stage of the disease.37%（HR=0.626; p<0.0001）。

Source: PCNS Conference Eli Lilly PPT

In terms of safety, 24% of patients in the Donanemab group experienced amyloid-related imaging abnormalities-edema (ARIA-E) confirmed by MRI, with 6% experiencing symptomatic ARIA-E; 31.4% of patients in the Donanemab group had cerebral microhemorrhages and superficial siderosis (ARIA-H), compared to 13.6% in the placebo group. The majority of ARIA cases were mild to moderate in severity, with a serious ARIA incidence rate of 1.6%, including two patients who developed ARIA and severe ARIA.And Dieof patients; 8.7% of patients experienced infusion-related reactions, most of which were mild to moderate.

Source: PCNS Conference Eli Lilly PPT

▌Key Issues and Voting Results

Key Issue 1:Can the existing data prove the efficacy of Donanemab treatment?Early Symptomatic ADEffectiveness?Donanemab inHow effective are the subgroups with different levels of tau protein?

Source:PCNS Conference

Background:Eli Lilly inIn the TRAILBLAZER-ALZ 2 study, early symptomatic AD patients with low/medium/high tau protein levels were included, while those with undetectable or extremely low levels were excluded.Patients with tau protein levels;TRAILBLAZER-ALZ 2 StudyThe safety extension study additionally includedPatients with undetectable or extremely low levels of tau protein. The results show that,Donanemab inLow/MediumEfficacy in the population with tau protein levels is superior to highPopulation with tau protein levels;Patients with undetectable or extremely low levels of tau protein also benefited from the treatment.。

Voting Results:11:0 Vote in FavorExisting data can prove the efficacy of Donanemab in treating early symptomatic AD.

Source: PCNS Conference

Key Issue 2:Early symptomatic AD patients receiveAfter Donanemab TreatmentOverall benefit-risk profile?

Source:PCNS Conference

Background of the issue:InTRAILBLAZER-ALZ 2 StudyIn China,Patients in the Donanemab groupThe rate of decline in iADRS scores was significantly slowed, but still declining.Smaller amplitude;At weeks 24, 52, and 76 of treatment17%, 42%, and 60% of patients, respectivelyAble to discontinue medication; lecanemab has not currently considered a discontinuation plan; 3 patients died due to ARIA in the study.

Voting Results:11:0Vote in favorEarly symptomatic AD patients experience overall benefits that outweigh the risks after receiving Donanemab treatment.

Source: PCNS Conference

After this battle,Donanemab is expected to see the light at the end of the tunnel. Looking forward to the FDA's regulatory decision!

References:

[1] PPT and other materials:https://www.fda.gov/advisory-committees/advisory-committee-calendar/updated-public-participation-information-june-10-2024-meeting-peripheral-and-central-nervous-system#event-materials

[2] PCNS Conference Live Replay: https://youtube.com/live/LPdOPydM18E

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article in a prominent position;For reprint, please leave a message or send a message to the WeChat Official Account backend, and indicate the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be directly used as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.