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.

In an unusual reversal, key drug regulators in Europe are now saying Leqembi, a high-profile medicine for Alzheimers disease, should be approved there, though only for patients less likely to experience a certain kind of concerning side effect.Leqembis primary developer, Japan-based Eisai, submitted a marketing application to the European Medicines Agency in early 2023. After some delays, the agency concluded this summer that the drugs safety risks outweigh its potential benefits. Chief among those risks was the frequent occurrence of a side effect known as ARIA,which can present as brain swelling and small-scale bleeding.Eisai appealed the EMAs so-called negative opinion. The appeal process takes about four months and assigns different reviewers to assess the application. Its also rarely successful for drug developers. Analysts at the investment firm RBC Capital Markets crunched the numbers and found that, over the past decade, the EMAs main drug review committee has changed its mind only 20% of the time.But Leqembi beat the odds. The committee said Thursday it supports approval for patients with mild cognitive impairment or mild dementia due to Alzheimers, who have one or no copies of a gene believed to increase the risk of ARIA. According to Jefferies analyst Michael Yee, around 60% to 80% of the Alzheimers population in Europe fits that genetic profile. Yee also noted that Leqembi seems more effective in this type of patient, which may therefore help justify its price and reimbursement to European payers.However, the recommendation also comes with a caveat that measures be in place to reduce the risk of severe and symptomatic ARIA and monitor its consequences in the long term. The committees new opinion will be sent to the European Commission, which makes the ultimate verdict on what drugs receive marketing authorization in the EU.On one hand, we believe the single-payer healthcare systems in Europe could enable fewer bureaucratic hurdles than were faced in the U.S. around screening, drug administration, and monitoring, which could enable smoother ultimate uptake, wrote RBC analyst Brian Abrahams in a note to clients Thursday. Even so, there may be time lags and uncertainty on reimbursement, and the drugs price will likely be lower than its U.S. tag of roughly $11,000 per patient.Although Leqembis entrance into the EU market is an overall positive, we expect [Biogen] and Eisai to face commercial hurdles similar to the U.S., which has led to relatively tepid uptake dynamics so far, wrote Piper Sandler analyst Christopher Raymond in his own note to clients.A sign outside Biogens Cambridge, Massachusetts, offices shows the companys logo on Sept. 5, 2024.Jacob Bell/BioPharma DiveEisai and its partner Biogen work together commercializing Leqembi, and initially hoped European regulators would clear the drug for a broader group of Alzheimers patients. Yet, even a narrower approval could significantly boost sales.Abrahams has estimated that peak annual Leqembi sales would reach $8.3 billion, with 20% coming from the European market.Eisai recorded 10 billion yen, or about $66 million, in Leqembi revenue between July and September. Biogen said the drugs improving sales are one reason the company expects to do better on a key metric of financial health this year.Leqembi is designed to combat Alzheimers by breaking up clumps of toxic proteins. These amyloid beta proteins have long been seen as a root cause of the disease, making them a prime target for pharmaceutical researchers. Kisunla, a recently approved product from Eli Lilly, also works on amyloid beta, as does another medicine from the Eisai and Biogen partnership, Aduhelm, though that drug was shelved following a series of commercial setbacks.In making its decision, the EMAs committee pointed to clinical data showing the differences in ARIA rates among participants who had one or no copies of that risk gene, and those with two. In that former group, nearly 9% and 13% of those who got Leqembi experienced brain swelling and microbleeding, respectively, while the rates among those who got a placebo were 1.3% and 6.8%.Among all the participants who got Leqembi, the rates of ARIA brain swelling and microbleeding were 12.6% and 16.9%.As for effectiveness, the committee said the benefits of Leqembi in the restricted population are in line with those seen in the broader population. Regulators in the U.S., Japan, China and a handful of other countries have already approved Leqembi based on evidence that it slows the progression of Alzheimer's around 27% an effect described as modest by some experts. '