Lecanemab

More than half of people with Down syndrome develop Alzheimer’s dementia as they age, with telltale bundles of amyloid and tau proteins forming in many of their brains by the age of 40.\n Ionis Pharmaceuticals has pulled the plug on an early investigational treatment for Alzheimer’s disease in people with Down syndrome, marking another setback for a group of patients who are both at higher risk for the neurodegenerative condition and not served by currently approved therapies.The California biopharma terminated a phase 1 trial of ION269 and has dropped the candidate from its pipeline, an Ionis spokesperson confirmed to Fierce Biotech.“This decision was made based on multiple factors, including slow enrollment, and is not related to concerns with the study drug,” the spokesperson said. After kicking things off in December 2024, Ionis has now shut down the trial with just one patient enrolled, according to the federal clinical trial database.With ION269 shelved, Ionis is instead focusing on other “high potential programs” in its neurology pipeline, the spokesperson added, including a phase 3 program for a rare genetic disease called Angelman syndrome. More than half of people with Down syndrome develop Alzheimer’s dementia as they age, with telltale bundles of amyloid and tau proteins forming in many of their brains by the age of 40, according to the National Institute on Aging.Despite this increased risk, neither Eli Lilly’s Kisunla (donanemab) nor Biogen and Eisai’s Leqembi (lecanemab) has been tested in people with Down syndrome. These antibodies, the only two disease-modifying medicines for the disease, target amyloid plaques in the brain. “Unfortunately, no one with Down syndrome was included in the clinical trials of Kisunla, nor in any of the previous trials in this drug class,” Hampus Hillerstrom, CEO of advocacy group LuMind IDSC, said in a statement when Kisunla was approved in July 2024. “So, we still don’t know if Kisunla or any other anti-amyloid drugs are safe for people with Down syndrome.”While Kisunla and Leqembi have demonstrated their ability to clear amyloid plaques, their ability to slow cognitive decline is typically modest, and both come with a risk of a dangerous brain bleeding side effect called amyloid-related imaging abnormalities, or ARIA. Studies have found that people with Down syndrome are at higher risk of suffering Alzheimer’s-related brain bleeds, and the appropriate use recommendations for both Kisunla and Leqembi advise not giving the meds to people with Down syndrome.Lilly has expressed a commitment to testing Kisunla in Alzheimer’s patients with Down syndrome. A trial testing donanemab in around 60 people with Down syndrome is set to kick off in August, according to the federal clinical trials database.A host of other anti-amyloid antibodies, specifically designed to reduce the risk of ARIA, are also in the works, including candidates from Roche, AbbVie, Denali Therapeutics and newcomer Korsana Biosciences. These antibodies, too, though, are not being developed with Down syndrome patients in mind.

Ionis Pharmaceuticals has ended the development of a potential medicine for people with Down syndrome who are at risk of Alzheimer’s disease, Endpoints News has learned. A spokesperson for the California biotech confirmed that the company terminated a Phase 1b test of the asset, dubbed ION269, for “multiple factors, including slow enrollment.” The decision was not related to concerns with the drug, and the company doesn’t have plans to advance the asset, the spokesperson said in a Friday email. The trial , codenamed Hero, enrolled only one participant out of an original target of 30 . The antisense oligonucleotide aimed to tamp down on production of a protein key to Alzheimer’s. The Alzheimer’s Association says that by age 40, most individuals with Down syndrome have significant levels of the proteins beta-amyloid and tau in their brains, according to autopsy studies. Abnormal amounts of those proteins can be signs of Alzheimer’s, and multiple drugmakers are going after them. Eli Lilly’s Kisunla and Biogen and Eisai’s Leqembi are directed at amyloid plaques. Alzheimer’s affects about 30% of people with Down syndrome who are in their 50s. The percentage increases as people age. About half of people in their 60s with Down syndrome have Alzheimer’s, according to the National Down Syndrome Society. ION269 was one of multiple wholly-owned assets in Ionis’ pipeline. The biotech has historically teamed up with larger drugmakers to commercialize its medicines, but it has started to market treatments on its own. Ionis still has a suite of collaborations, with five Phase 3 readouts expected this year from its partnered pipeline. One of them, bepirovirsen for chronic hepatitis B, already had positive results. The company’s wholly-owned pipeline includes late-stage assets like zilganersen for Alexander disease and ION582 for Angelman syndrome. The company has several mid-stage medicines in development for other neurology conditions. Ionis has also out-licensed some of its portfolio in the past year, including a rare blood disorder drug to Ono Pharmaceutical and a hypertension treatment candidate to Kardigan .