Voyager Therapeutics is tripling down on its Alzheimer’s disease franchise, this time with a gene therapy aimed at amyloid-beta plaques.
The company broke the news on its second-quarter earnings call with investors, during which CEO Alfred Sandrock, M.D., Ph.D., cited recent momentum behind anti-amyloid beta antibodies—like the regulatory approval of Eisai and Biogen’s Leqembi—as part of the impetus for the move. Voyager already has two programs in its pipeline targeting tau, the other key protein thought to drive Alzheimer’s etiology.
“I think of amyloid as the trigger, and tau as the bullet,” Sandrock said. “There’s a tipping point at which increasing amounts of amyloid cause tau to spread, and that spread of tau is what causes neurodegeneration.” The CEO pointed to Eli Lilly's data from a late-stage clinical trial of its anti-amyloid-beta antibody donanemab, which showed that it was more likely to be effective in patients who had lower levels of tau.
“Ultimately, we need to better understand the clinical efficacy of anti-amyloid treatments by stage and subtype,” he added. “Complete responders may not need more treatment than anti-amyloid, but partial responders may be appropriate for a combination of anti-amyloid and anti-tau, and nonresponders may be candidates for switching to anti-tau monotherapy.”
Voyager's new gene therapy is composed of an anti-amyloid beta antibody encoded in a viral vector and delivered in the company’s TRACER capsids. Voyager thinks the treatment could be superior to intravenously infused anti-amyloid antibodies because it may be less likely to cause amyloid-related imaging abnormalities, or ARIA, a group of dangerous neurological side effects characterized by abnormal MRI findings. Reports of ARIA have dogged anti-amyloid antibodies, including donanemab and Leqembi.
Both presence of the same APOE4 gene variant that predisposes people to Alzheimer's and the size of the initial dose have been linked to the development of ARIA. There is “biologic rationale” to suggest that gene therapy wouldn’t confer the same degree of risk, Voyager Chief Scientific Officer Todd Carter, Ph.D., said on the earnings call.
“In a gene therapy approach, the anti-amyloid antibodies are steadily secreted by cells in the central nervous system, and thus we’d be avoiding high antibody concentrations that necessarily follow intravenous antibody infusions,” he said. “Moreover, the antibody would first engage the beta amyloid deposited in and around beta amyloid plaques rather than around blood vessels, thus avoiding ARIA.”
Still, some risk does remain, Sandrock acknowledged on the call. The company is considering several mitigation strategies to handle ARIA if it does arise, including the use of a small molecule to control gene expression.
Voyager hasn’t yet disclosed which anti-amyloid antibody it’s vectorizing, instead telling an analyst on the call that the company has been exploring “several options.”