An experimental Alzheimer’s illness remedy designed by Alzheon to cut back depositions of amyloid plaque within the mind didn’t beat a placebo in a Part 3 examine, the newest blow to a drug whose historical past is marked by medical trial shortfalls.
The twice-daily capsule, valiltramiprosate, didn’t meet the primary medical trial aim of slowing cognitive decline measured at 78 weeks, Alzheon introduced Thursday. Nonetheless, the Framingham, Massachusetts-based firm pointed to measures of mind quantity displaying a slowing of mind atrophy, which it mentioned counsel potential neuroprotective advantages of the drug.
Alzheon additionally famous nominally statistically vital cognitive advantages and clinically significant practical results in a prespecified subgroup — sufferers on the earliest phases of the illness. That’s a subgroup of the genetically outlined affected person subgroup Alzheon had hoped would profit from drug.
The Alzheon drug, recognized in earlier phases of improvement as ALZ-801, was licensed from Quebec-based Bellus Well being in 2013. That biotech’s small molecule, known as tramiprosate, was designed to bind to beta amyloid. The hope was this strategy might stop the aggregation of amyloid plaque within the brains of Alzheimer’s sufferers. However outcomes from two Part 3 research carried out by the Canadian firm confirmed the drug didn’t result in statistically vital enchancment in cognitive perform.
Alzheon’s evaluation of the tramiprosate knowledge discovered variability in blood ranges of the drug in examine members. Valiltramiprosate is a prodrug of tramiprosate, which suggests it converts to tramiprosate within the physique. Alzheon’s adjustments to the Bellus drug embrace enchancment in how the compound is absorbed within the physique with a aim of decreasing the variability noticed in earlier checks. Alzheon’s evaluation of the earlier trial knowledge additionally discovered indicators of enchancment in sufferers who carry the ApoE4 gene, a variant that will increase the danger of creating Alzheimer’s. Alzheon’s Part 3 check enrolled 325 sufferers who carry two copies of ApoE4.
The brand new Alzheimer’s drugs permitted by the FDA prior to now two years, Leqembi from Eisai and Kisunla from Eli Lilly, are antibodies, giant molecule medication administered by infusion. Alzheon hoped its oral drug would provide sufferers the benefit of a better dosing formulation.
There was additionally potential for a security edge. The anti-amyloid antibody medication introduce the danger of mind irritation and bleeding known as amyloid-related imaging abnormalities (ARIA). ApoE4 carriers have a considerably larger threat of creating ARIA, so Alzheimer’s sufferers who carry this genetic variant may gain advantage from a drug providing a distinct strategy. Whereas Leqembi and Kisunla could also be used to deal with such sufferers underneath their FDA approvals, the labels of those merchandise carry black field warnings that flag this larger complication threat. This threat has additionally been a sticking level for efforts to safe regulatory approvals in Europe and Australia.
Alzheon reported no critical adversarial reactions and no deaths within the Part 3 check of valiltramiprosate. The corporate additionally mentioned there was no elevated threat of ARIA. Alzheon plans to publish extra detailed Part 3 ends in a peer-reviewed publication. Regardless of lacking the primary aim of the pivotal check, Alzheon just isn’t abandoning the drug. Within the firm’s announcement of the examine’s preliminary outcomes, Chief Medical Officer Susan Abushakra mentioned sufferers who’ve two copies of ApoE4 “have a determined want for extra remedy choices.”
“A precision drugs strategy is essential to addressing the wants of Alzheimer’s sufferers who’ve the ApoE4/4 genotype, and we’re dedicated to this affected person inhabitants,” she mentioned.
A protracted-term extension examine is continuous to judge sufferers who accomplished the Part 3 check of valiltramiprosate. This examine, ongoing within the U.S., U.Okay., and Canada, is following sufferers for an extra 52 weeks. Final June, privately held Alzheon raised $100 million in Sequence E financing to assist completion of the pivotal examine and put together for potential commercialization of its Alzheimer’s drug. The Part 3 program can be supported by $51 million in grant funding from the Nationwide Institutes of Well being’s Nationwide Institute on Growing old.
Photograph: Yuichiro ChinoImage, Getty Photographs
