Donanemab-AZBT

The Knight Family DIAN-TU platform trial was initiated in 2012. Image credit: Shutterstock / Orawan Pattarawimonchai. Roche’s discontinued Alzheimer’s disease drug has shown signs that it could prevent onset of the disease. The Phase II/III Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU) platform trial (NCT05552157), was conducted by researchers at the Washington University School of Medicine. The study evaluated Roche’s gantenerumab in 73 participants aged between 30 to 50 with rare, inherited genetic mutations that cause the overproduction of amyloid in the brain, which investigators say all but guarantees they will develop Alzheimer’s disease in middle age. The participants were dosed in the DIAN-TU-001 (NCT01760005) and the open-label extension (OLE) (NCT06424236) studies. Data from the DIAN-TU-001 trial showed that Roche’s gantenerumab, an amyloid beta peptide inhibitor, reduced amyloid levels in the brain and improved some measures of Alzheimer’s proteins, but did not meet the primary endpoint. Now, new OLE study data published in The Lancet has shown the anti-amyloid drug cut the risk of developing symptoms by 50%. For a subgroup of 22 participants who had no cognitive problems at the study’s start and who received the drug the longest – an average of eight years – the treatment cut the risk of developing symptoms, according to a primary analysis of the data and supported by multiple sensitivity analyses supporting the trend. The investigator’s calculation not only considers how many people developed symptoms but also when symptoms emerged for each participant compared to his or her expected age of onset. That means the effect size could change as time goes on. Investigators said that some participants in the study are at or just past their expected age of onset and if they continue to go without developing symptoms, the effect size will increase. However, if some who are healthy now develop symptoms in later years, this would reduce the effect size. The Charles F and Joanne Knight Distinguished Professor of Neurology at Washington University School of Medicine, Dr Randall Bateman, said: “We don’t yet know how long they will remain symptom-free – maybe a few years or maybe decades.” The DIAN-TU-001 study was launched in 2012, and all participants in the trial had no to very mild cognitive decline and were within the range of 15 years before to ten years after their expected age of Alzheimer’s onset, based on family history. When the trial concluded in 2020, it was not clear whether Roche’s therapy would provide cognitive benefit to those without symptoms. This caused investigators to launch the OLE study to evaluate gantenerumab’s effects and determine whether higher doses or longer treatment could prevent or delay cognitive decline. Investigators hope that this result could also translate to those at risk of late-onset Alzheimer’s disease. “If late-onset Alzheimer’s prevention trials have similar results to the DIAN-TU trials, there soon could be Alzheimer’s preventions available for the general population,” Bateman added. “I am highly optimistic now, as this could be the first clinical evidence of what will become preventions for people at risk for Alzheimer’s.  One day soon, we may be delaying the onset of Alzheimer’s disease for millions.” Patients switched to Leqembi The therapy was discontinued after Roche’s Phase III programme as the GRADUATE I and II studies failed to meet their endpoints . As a result, participants receiving gantenerumab in DIAN-TU OLE were switched to Eisai and Biogen’s anti-amyloid therapy Leqembi (lecanemab). Another study, the DIAN-TU-002 trial (NCT06647498), has been launched as part of the platform series, evaluating Eli Lilly’s remternetug in young adults to assess its efficacy as a preventative of the disease. Eli Lilly is already a big name in the Alzheimer’s disease space after the launch of the anti-amyloid therapy Kinsula (donanemab). An issue with anti-amyloid drugs such as Leqembi, Kinsula and gantenerumab is the adverse event (AE) amyloid-related imaging abnormalities (ARIA). In the OLE study of gantenerumab, ARIA rates were one-third higher than in the original clinical trial (30% versus 19%), which the researchers attribute to the higher doses used in the extension. Two participants developed such severe ARIA that they needed to be taken off the drug, at which point they recovered. There were no life-threatening AEs or deaths. The global Alzheimer’s disease market across the eight major markets (8MM: US, France, Germany, Italy, Spain, UK, Japan, and China) is forecast to grow from $2.4bn in 2023 to $19.3bn by 2033, according to GlobalData. GlobalData is the parent company of Clinical Trials Arena .

Vaccinex’s lead asset is being evaluated in neurodegenerative and oncological indications. Image credit: Shutterstock/interstid. Despite reporting positive Phase II results for its lead candidate last year, Vaccinex will soon no longer be a publicly traded company after falling short of Nasdaq requirements. The US-based company will delist its shares of common stock from Nasdaq via a Form 25 it intends to submit to the Securities and Exchange Commission on or around the 17 March. Form 25s are used by public company to officially delist their securities from a stock exchange, with delisting becoming effective 10 days after the document is filed. Vaccinex, currently listed on Nasdaq under the ticker VCNX, had its common stock trading suspended in December 2024 following a hearings panel from Nasdaq amidst financial shortcomings. Nasdaq notified Vaccinex of delisting intentions after equity requirements for companies trading on the stock exchange were not met. Vaccinex went public in 2018, raising around $40m to advance its pipeline of neurodegenerative disease therapies. The initial public offering (IPO) was priced at $12 per share, though share prices have since plummeted – arriving at $3.82 by the start of December 2024. Vaccinex’s market cap is currently just shy of $2.5m. As with many early-stage companies, Vaccinex funnelled the majority of its resources into a lead candidate. The asset, called pepinemab, is an antibody being evaluated in neurogenerative diseases and cancer indications. As pepinemab advanced through studies, Vaccinex’s research and development expenses grew. As per its most recent quarterly results ending September 2024, Vaccinex was left with just $2.9m in cash. Vaccinex affirmed it “plans to continue to focus on development of its lead product, pepinemab, to treat Alzheimer’s disease and cancer through partnerships, grants and other financing avenues.” Pepinemab, previously called pepinemabin, has shown promise, producing positive topline results in a Phase Ib/II trial (NCT04381468) in patients with Alzheimer’s disease in July 2024. Vaccinex reported that its asset, given as a monotherapy, resulted in a statistically significant increase in FDG-PET signal in areas of the brain known to be affected by early disease progression. The drug was also investigated in Huntington’s disease, with similar Phase II safety profile and brain metabolic activity effects. Judging by lack of investor enthusiasm in the company, Vaccinex has found the pressures from already-marketed Alzheimer’s therapies hard to repel. Eisai and Biogen’s Leqembi (lecanemab) and Eli Lilly’s Kisunla (donanemab) dominate the landscape, winning approvals in the US in 2023 and 2024 respectively. Leqembi is forecast to see $5.3bn in global revenues by 2030, with Kisunla expected to generate $1.7bn by the same year, according to GlobalData’s Pharma Intelligence Centre. GlobalData is the parent company of Pharmaceutical Technology . Despite its delisting, Vaccinex will also continue to focus on pepinemab in oncology indications. The antibody is evaluated in combination with MSD’s Keytruda in the Phase Ib/II KEYNOTE-B84 study (NCT04815720) in recurrent or metastatic head and neck cancer (HNSCC). Vaccinex has also teamed up with Merck KGaA to test pepinemab in combo with Bavencio (avelumab) in a Phase Ib/II study in patients with metastatic pancreatic adenocarcinoma (PDAC).