Lifetime Achievement Award
Focused ultrasound technique leads to release of neurodegenerative disorders biomarkers
Update on the DIAN-TU-001 Trial with E2814 and Lecanemab (Eisai Co., Ltd)
The statement below is in response to Eisai’s 06 January 2023 announcement regarding the FDA’s accelerated approval of lecanemab for the treatment of symptomatic Alzheimer’s disease (AD).
On January 6th, 2023, the FDA announced approval of lecanemab (an anti-amyloid beta (Aβ) protofibril antibody) through its Accelerated Approval Program 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.
DIAN-TU recognizes the importance of this approval for patients with Alzheimer’s disease symptoms. Eisai and the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) at Washington University in St. Louis, Missouri have previously announced a collaboration to include lecanemab in the DIAN-TU Tau NexGen trial to be tested with E2814 – an experimental immunotherapy targeting the microtubule binding domain of the tau protein.
“This approval is a very important step forward in the treatment of Alzheimer’s disease. Our partnership with Eisai to include lecanemab in our combination trial will continue to move the field forward,” said principal investigator Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology and the director of DIAN-TU.
The DIAN-TU NexGen trial of E2814 and lecanemab is currently recruiting participants [Clinicaltrials.gov NCT05269394].
FDA APPROVES LEQEMBI™ (LECANEMAB-IRMB) UNDER THE ACCELERATED APPROVAL PATHWAY FOR THE TREATMENT OF ALZHEIMER’S DISEASE
Update on the DIAN-TU-002 Primary Prevention Trial
20 December 2022
Update on the DIAN-TU-002 Primary Prevention Trial
The statement below is an update to the 15 November 2022 announcement by the Knight Family Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) regarding the DIAN-TU-002 Primary Prevention Trial with Gantenerumab.
During the presentation of topline results from GRADUATE I and II studies at the Clinical Trials in Alzheimer’s Disease (CTAD) conference in San Francisco, Roche announced its decision to discontinue the company’s clinical trials of gantenerumab, including the GRADUATION, OpenRoAD, PostGraduate and SKYLINE trials. After further consideration and consultation, the DIAN-TU has decided to pause the DIAN-TU-002 Primary Prevention Trial launch activities related to gantenerumab while continuing to evaluate the risk and benefits of gantenerumab in the DIAN-TU-001 trial [Clinicaltrials.gov #NCT01760005]. “Based on the effect of gantenerumab on amyloid biomarkers in the previous DIAN-TU-001 study and the recent GRADUATE studies, and because we are testing higher doses than those tested in the GRADUATE studies, we still believe there is good reason to evaluate gantenerumab in the Primary Prevention Trial,” said Dr. Eric McDade, Co-Director of the DIAN-TU and Principal Investigator of the DIAN-TU-002 Primary Prevention Trial. “However, we have a responsibility to our participants and stakeholders to ensure the treatment is available to enable completion of the Primary Prevention Trial. This is no longer possible with gantenerumab.”
To prepare for the inclusion of another study drug in the DIAN-TU-002 platform, the DIAN-TU is resuming enrollment of Primary Prevention participants in the cognitive run-in period. This run-in period is intended to improve the study’s statistical power, continue engagement of participants, and decrease total duration of the trial once a drug arm opens for enrollment.
“The Alzheimer’s Association fully supports making decisions about the 002 primary prevention trial based on the latest science, while always keeping the study participants’ needs at the center of all study-related actions,” said Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer. “We trust the DIAN-TU study leaders to make the right decision and then move forward with this important clinical trial.”
The DIAN-TU trial platform was designed to quickly adapt to new information about investigational drugs so drug arms could be terminated or added as needed. With current funding from the NIA/NIH (U01AG059798, PI EM McDade) and the Alzheimer’s Association, the DIAN-TU will continue site and vendor readiness activities while evaluating multiple drug programs for potential use in the DIAN-TU-002 Primary Prevention Trial.
The DIAN-TU is informing study participants and applicable health authorities, study ethics committees, and institutional review boards about the decision on the DIAN-TU-002 trial. Dosing in the DIAN-TU-001 Open Label Extension will continue [Clinicaltrials.gov #NCT01760005] as designed.
WashU, Eisai form drug discovery collaboration
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].