Donanemab-AZBT

PHOENIX, Nov. 14, 2024. A new Alzheimer's prevention study has received a $74.5 million five-year grant from the National Institute on Aging, part of the National Institutes of Health (NIH). The two-part study will be conducted in members of the world's largest autosomal dominant Alzheimer's disease (ADAD) kindred in Colombia who carry a genetic mutation that makes them all but destined to develop Alzheimer's and become cognitively impaired at an average age of 44. The study is led by Banner Alzheimer's Institute in Phoenix and the Neurosciences Group at the University of Antioquia (GNA) in Medellin, Colombia. It will initially aim to remove amyloid plaques as completely as possible in cognitively impaired and unimpaired carriers of the presenilin 1 (PSEN1) E280A mutation, and then evaluate different ways to stave off the recurrence of plaque deposits and other ensuing elements of the disease. Enrollment is expected to begin in the fall of 2025. The first part of the study will use Eli Lilly and Company's (Lilly) antibody therapy donanemab to remove existing plaques as completely as possible (i.e., to levels consistent with a negative amyloid PET scan). Donanemab has been shown to clear amyloid plaques and slow cognitive decline, and was recently approved by the U.S. Food and Drug Administration for use in patients with mild cognitive impairment and dementia due to Alzheimer's. The study will provide new information about the drug's safety, tolerability, and biological efficacy in the unimpaired and impaired stages of ADAD. The second part of the study will compare the following approaches in the same participants, for safety, tolerability and ability to avert amyloid plaque accumulation and other biological and clinical features of the disease: This study builds on the history, partnership, infrastructure and learnings of the original API ADAD Colombia Trial, which launched a new era in Alzheimer's prevention research when it was announced by NIH in 2012. While the investigational drug in the original trial with crenezumab failed to clear plaques or demonstrate a clinical benefit, the study introduced paradigms to speed up the evaluation of promising prevention therapies, found ways to do so in a vulnerable population in a developing country, and led to a growing number of prevention trials, some of which may find the first effective Alzheimer's prevention therapies within the next few years. Both the original and the new trial tap into GNA's identification of about 6,000 distant relatives from the Colombian PSEN1 E280A kindred, including about 1,200 who carry the ADAD-causing genetic mutation. "We are excited about the chance to advance the fight against Alzheimer's disease in partnership with our outstanding colleagues and these unique families in Colombia," said Robert Alexander, MD, the API's chief scientific officer and one of the prevention trial leaders. "This study will clarify the extent to which the antibody treatment reduces amyloid plaques in the unimpaired and impaired stages of ADAD and test different approaches to maintain low amyloid levels following plaque removal." The new study will enroll 200 cognitively unimpaired and mildly impaired mutation carriers and 40 non-carriers (who will receive placebo) from the Colombian kindred. "This trial is a testament to our dear friend and longstanding partner, Dr. Francisco Lopera, who established GNA, forged a close working relationship with API, and could not have been more committed to these families," said Eric M. Reiman, MD, executive director of Banner Alzheimer's Institute and one of the other API leaders. "He constantly said, 'My families are waiting,' and he played indispensable roles in the effort to find effective prevention therapies." "I am honored to follow in Dr. Lopera's footsteps and continue our work with API," said David Aguillón, MD, GNA's new director and principal investigator of the University of Antioquia study site. "Dr. Lopera and the Antioquia families have inspired all of us to never give up, to maintain our sense of urgency to find effective Alzheimer's prevention therapies, and to do so in ways that will help our Antioquia families." The research study is supported by grant R01AG086363 from the NIH National Institute on Aging, the lead U.S. federal agency supporting and conducting Alzheimer's disease and related dementias research. Lilly and Roche are generously donating the drug supplies that will be evaluated in this study. The study is led by Drs. Robert Alexander, Eric Reiman and Jessica Langbaum from BAI and its API; David Aguillón from the University of Antioquia; and Yakeel Quiroz from the University of Antioquia and Massachusetts General Hospital. API also received a $3 million grant from the Zurich-based NOMIS Foundation to continue to assess about 2,000 mutation carriers and non-carriers from the PSEN1 E280A kindred, provide a shared resource of longitudinal data and blood samples for the field, accelerate enrollment in the new prevention trial, and provide education and social support for the families irrespective of their participation in the study. About Banner Alzheimer's Institute Since its inception in 2006, Banner Alzheimer's Institute has sought to find effective Alzheimer's disease prevention therapies within twenty years, establish a new model of care for cognitively impaired patients and family caregivers, and forge new models of collaboration in biomedical research. It has made groundbreaking contributions to the unusually early detection, tracking, diagnosis, study and prevention of Alzheimer's disease. It includes the pioneering Alzheimer's Prevention Initiative, an extensive profile of research studies and clinical trials, comprehensive clinical, family and community service programs, leading brain imaging and blood-based biomarker research programs, and strategic partnerships with public and private research organizations around the world. About the Alzheimer's Prevention Initiative The Alzheimer's Prevention Initiative (API) is an international collaborative formed in 2009 to launch a new era of Alzheimer's prevention research. Led by Banner Alzheimer's Institute, the API conducts prevention trials in cognitively healthy people at increased risk for Alzheimer's disease. API continues to establish brain imaging, fluid biomarker and cognitive endpoints needed to rapidly test promising prevention therapies. It also leads participant recruitment registries to accelerate enrollment into Alzheimer's-focused studies. API is intended to provide the scientific means, accelerated approval pathway and enrollment resources needed to evaluate the range of promising Alzheimer's prevention therapies and find ones that work without losing another generation. For more information, go to alzheimerspreventioninitiative.com. About Grupo de Neurociencias de Antioquia Grupo de Neurociencias de Antioquia (GNA), at the University of Antioquia in Medellín, is ranked as one of the best research organizations in Colombia. For more than three decades, GNA has characterized what is now considered the world's largest population with early-onset familial Alzheimer's disease, and it continues to play pioneering roles in the effort to find effective Alzheimer's prevention therapies. GNA has also characterized large and paradigmatic populations with other forms of dementia and other neurogenetic disorders. SOURCE Banner Alzheimer's Institute Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

The EMA’s Committee for Medicinal Products for Human Use has issued a positive recommendation for Eisai and Biogen’s Leqembi (lecanemab) as a treatment for Alzheimer’s disease. This recommendation applies to only those patients who carry one or no copies of a gene variant called ApoE4. Image credit: Shutterstock/DavideAngelini The European Medicines Agency (EMA) has reversed its stance on Biogen and Eisai ’s Alzheimer’s therapy, Leqembi (lecanemab), now recommending its approval for a specific subset of patients after initially rejecting it in July 2024. In July, the EMA’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on Leqembi, citing concerns over its safety and efficacy when used broadly in patients with early Alzheimer’s disease. At the time, the committee highlighted the therapy’s risk of causing amyloid-related imaging abnormalities (ARIA), which may indicate brain swelling, fluid buildup, or bleeding visible on MRI scans. They also argued that Leqembi’s effect in delaying cognitive decline was “not large enough” to offset these risks in a wider patient population. However, following a re-examination requested by the company, the CHMP now recommends Leqembi for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease, provided they carry only one or no copies of a gene variant called ApoE4. These patients are believed to face a lower risk of developing ARIA than those with two copies of ApoE4. The CHMP’s revised recommendation is based on new subgroup analyses that excluded data from patients with two copies of ApoE4, who are at the highest risk of ARIA. Among patients treated with Leqembi, 8.9% of those with one or no copies of ApoE4 experienced ARIA-E (brain swelling), compared to 12.6% in the broader patient group. Similarly, ARIA-H (brain bleeding) was observed in 12.9% of the restricted group, versus 16.9% of all patients. For comparison, placebo-treated patients in the restricted group experienced ARIA-E and ARIA-H at rates of 1.3% and 6.8%, respectively. The EMA is expected to make a final decision on the marketing authorisation application of Leqembi based on the CHMP recommendation in January 2025. To mitigate risk, the EMA has said that Leqembi will be accessible through a controlled programme, allowing use only in the recommended patient group. Patients will undergo magnetic resonance imaging (MRI) scans to monitor for ARIA before starting treatment and again before the 5th, 7th, and 14th doses, with additional scans as needed if symptoms arise. Leqembi, which targets amyloid plaques in the brain—a hallmark of Alzheimer’s thought to impair memory and cognition—received accelerated approval from the US Food and Drug Administration (FDA) in January 2023, which was converted to full approval in July 2023. Earlier this month, however, Eisai had to adjust its sales forecast for Leqembi, lowering it by $90m to $280m (¥42.5 billion) for the second half of the 2024 fiscal year. The company cited delays in US revenue as the main reason for lowering the revenue forecast. This year has seen both praise and scrutiny of Alzheimer’s therapies. In October, the UK’s National Institute for Health and Care Excellence (NICE) recommended against the broad use of Eli Lilly’s Kisunla (donanemab), while the EMA continues to review it. Kisunla works in a similar manner to Leqembi, designed to remove amyloid plaques from the brain. The number of people with Alzheimer’s in the eight major markets (US, France, Germany, Italy, Spain, UK, Japan, and China) is expected to grow from 21,921,200 in 2020 to 29,898,812 in 2030, as per GlobalData . GlobalData is the parent company of Pharmaceutical Technology.