ABvac-40

Grifols announced that its experimental ABvac40 vaccine achieved the primary endpoints of a Phase II study, confirming the jab's safety, tolerability and immune response in early-stage Alzheimer's disease patients. The findings were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference."Previous vaccines in development for Alzheimer's disease faced setbacks due to harmful meningoencephalitis side effects," remarked Jose Terencio, chief executive of Grifols' Araclon Biotech subsidiary, adding "we look forward to evaluating next steps for this programme."The study included 134 patients with amnestic mild cognitive impairment or very mild Alzheimer's disease. In Part-A, patients were randomised to receive a total of six doses, including one monthly single-dose injection of ABvac40 or placebo for the first five months, followed by a booster of ABvac40 or placebo at month 10. Part-B was an extension study with cross-over from Part-A, in which placebo patients in Part-A received ABvac40, while ABvac40-treated patients received placebo and a booster of ABvac40.Hints of cognitive benefitGrifols reported that ABvac40 induced a "robust immune response" against Aβ40 peptide, and also demonstrated "some potential cognitive benefits" in early-stage Alzheimer's patients, meeting the study's primary endpoints. The trial was not powered for finding efficacy on neuropsychological scales, although the company noted that the ABvac40-treated group saw as much as a 38% reduction in disease progression, based on the Mini-Mental State Examination (MMSE) score, suggesting ABvac40 could have "potential efficacy in addressing the cognitive decline" associated with the disease.Other neuropsychological tests, known as RBANS and TMT, which evaluate things like memory, visual scanning, language and attention, also showed "favourable results" with ABvac40 versus placebo, Grifols said, while the vaccine was associated with a smaller increase in whole-brain atrophy as well. However, the company indicated that "global or functional scales did not show differences" between the two groups.ABvac40 is designed to target the C-terminal end of the Aβ40 peptide, which Grifols says could help avoid immune triggers responsible for meningoencephalitis, a complication seen in earlier vaccines. Emerging research also suggests that Αβ40 plays a role in cerebral amyloid angiopathy (CAA), the company noted.According to Grifols, data presented at CTAD confirm preliminary findings indicating a comparable safety profile between ABvac40 and placebo, with similar rates of treatment-emergent adverse events. Further, there were no reports of cerebral oedema or aseptic meningo-encephalo-myelitis in the study, and "few instances" of micro-haemorrhages, with none leading to discontinuation, the company said.

Pictured: Alzheimer's disease illustration/iStock, Artur Plawgo Araclon Biotech has confirmed the safety of its experimental Alzheimer’s disease vaccine in an exploratory analysis of Phase II trial data. The Grifols Group company reported “encouraging” results on Tuesday in patients with mild cognitive impairment or mild early-stage AD as part of a late-breaking presentation at the 2023 Clinical Trials on Alzheimer’s Disease conference. ABvac40, an active vaccine against the Aβ40 peptide, had a favorable safety pro a robust immune response, the company reported. Research suggests Aβ40 plays a role in cerebral amyloid angiopathy, a prevalent condition in AD patients. “By specifically targeting the Aβ40 peptide, ABvac40 is tapping into a central mechanism believed to drive cognitive decline with potential to alter the course of disease,” Mercè Boada Rovira, a principal investigator of the study, said in a statement. Although the trial was not designed to test efficacy on cognitive impairment, the treated group showed as much as a 38% drop in disease progression compared to placebo based on the Mini-Mental State Examination score. The results suggest ABvac40 may address the cognitive decline aspect of AD. While tests including the Repeatable Battery for the Assessment of Neuropsychological Status and the Trial Making Test showed favorable results for ABvac40 versus the placebo group, global or functional scales did not show a difference in those treated compared to the placebo arm. “We are pleased to report final positive results from the Phase II study of ABvac40, including a robust immune response with some significant reduction in disease progression, all with a favorable safety profile,” Araclon CEO Jose Terencio said in a statement. The vaccine’s design targets the C-terminal end of the Aβ40 peptide, which the company believes prevents meningoencephalitis, simultaneous inflammation of the meninges and the brain. The side effect was seen in a previous first-generation vaccine two decades ago, when 6% of patients treated with Elan Pharmaceuticals AN1792 developed the life-threatening complication and product development was halted. Terencio mentioned previous setbacks due to meningoencephalitis, stating the recent Phase II results for ABvac40 validate its clinical potential. Araclon is now evaluating the next steps forward. Florida-based Vaxxinity has the most advanced vaccine targeting beta-amyloid in the clinic. The biotech’s Phase IIa data were published in August 2023, suggesting it could offer more competitive advantages over newly approved anti-amyloid therapies such as less frequent dosing, more convenient administration and potentially lower rates of ARIA-E. Vaxxinity has received Fast Track Designation from the FDA for its AD vaccine. However, it’s stalled a bit while seeking a strategic pharma partner to take it into Phase III. Kate Goodwin is a freelance life science writer based in Des Moines, Iowa. She can be reached at kate.goodwin@biospace.com and on LinkedIn.