Update on the DIAN-TU-001 Open Label Extension and DIAN-TU-002 Primary Prevention Trials with Gantenerumab (Roche/Genentech)

The statement below is in response to the 14 November 2022 announcement regarding the results from the GRADUATE I and II AD studies found on Roche’s website.

Roche, known as Genentech in the United States, and the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University in St. Louis have been evaluating gantenerumab in the DIAN-TU-001 secondary prevention trial, currently in an open label extension, and the two organizations previously announced a collaboration to evaluate gantenerumab in the DIAN-TU-002 primary prevention trial. The GRADUATE trials were not conducted in a dominantly inherited AD (DIAD) population, and it is possible that treatment outcomes from gantenerumab may be different in DIAD because DIAD is known to be caused by mutations in amyloid-beta processing. Importantly, the DIAN-TU trials include individuals that have no symptoms of AD and may provide an opportunity to test the effect of gantenerumab on preventing symptom onset. Further, the DIAN-TU-001 open label extension is testing a higher dose of gantenerumab than was tested in the GRADUATE trials and includes participants who will have been treated for 7-10 years, much longer than the GRADUATE I and II studies, providing an opportunity to test higher doses and longer treatment.

Dosing in the DIAN-TU-001 open label extension will continue [Clinicaltrials.gov #NCT01760005], with the primary prevention trial of gantenerumab scheduled to begin recruitment by the end of 2022 [Clinicaltrials.gov #NCT05552157]. Safety data from both trials will continue to be monitored by the DIAN-TU Data Safety Monitoring Board.  The data from the GRADUATE I and II studies will be analyzed in depth to assess potential implications for the DIAN-TU studies.  “Although the primary outcome was negative in the top-line results of the GRADUATE I and II trials, moderate amyloid removal and modest trends towards benefit across multiple clinical and cognitive outcomes in pre-specified analyses were observed,” said principal investigator Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology and the director of the DIAN-TU.  “In our ongoing secondary prevention open label extension trial in dominantly inherited Alzheimer’s disease, all participants receive higher doses of gantenerumab than used in the GRADUATE trials.  DIAD is a purer form of Alzheimer’s disease that is caused by amyloid, and with much higher doses of gantenerumab being used, these patients may have a better response.”  The DIAN-TU-001 open label extension followed the DIAN-TU-001 secondary prevention trials of gantenerumab and solanezumab, with an additional 3 years of treatment with gantenerumab.  Results are expected in mid-to-late 2024.  Dr. Eric McDade, Co-Director of the DIAN-TU and Principal Investigator of the DIAN-TU-002 primary prevention trial, added “Based on the effect of gantenerumab on amyloid biomarkers in the previous DIAN-TU-001 study, there is good reason for evaluating this investigational medicine before amyloid pathology begins to assess the benefit of amyloid prevention in DIAD.  However, further analysis of the GRADUATE study data will be necessary to best determine potential impact for long-term prevention.”

[Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on Phase III GRADUATE programme evaluating gantenerumab in early Alzheimer’s disease

Update on the DIAN-TU-001 Trial with E2814 and Investigational Lecanemab (Eisai Co., Ltd)

The statement below is in response to the 28 September 2022 announcement found on Eisai’s website.

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, “Biogen”) announced positive topline results from the large global Phase 3 confirmatory Clarity AD clinical trial of lecanemab (development code: BAN2401), an investigational anti-amyloid beta (Aβ) protofibril antibody for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain.

Eisai and the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University in St. Louis have previously announced a collaboration to include lecanemab in the DIAN-TU NexGen trial to be tested with  E2814 – an experimental immunotherapy targeting the microtubule binding domain of the tau protein. The positive results reported in the Clarity AD trial are highly impactful for the treatment of Alzheimer’s disease. “We are delighted about the report of beneficial effects in the Clarity Alzheimer’s disease trial and what this could mean for millions of Alzheimer’s disease patients,” said principal investigator Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology and the director of DIAN-TU.  “In our symptomatic and secondary prevention trials in dominantly inherited Alzheimer’s disease, all participants will receive lecanemab and in combination will be randomized to receive an anti-tau drug (E2814) or placebo.  We have scientific rationale that targeting both amyloid and tau could provide an even greater benefit than either alone.”

Because the Clarity AD trial was conducted in a non-dominantly inherited form of AD, it is possible that treatment benefits from lecanemab may be different in dominantly inherited AD (DIAD). The results of the Clarity AD trial support the investigational use of lecanemab in DIAD, and the DIAN-TU NexGen trial will continue with lecanemab as designed.  Safety data will continue to be monitored by the DIAN-TU Data Safety Monitoring Board.  The DIAN-TU NexGen trial of E2814 and lecanemab is currently recruiting participants [Clinicaltrials.gov NCT05269394].

LECANEMAB CONFIRMATORY PHASE 3 CLARITY AD STUDY MET PRIMARY ENDPOINT, SHOWING HIGHLY STATISTICALLY SIGNIFICANT REDUCTION OF CLINICAL DECLINE IN LARGE GLOBAL CLINICAL STUDY OF 1,795 PARTICIPANTS WITH EARLY ALZHEIMER’S DISEASE

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