AbbVie will partner with Voyager Therapeutics to develop and commercialize gene therapies for Alzheimer's disease and other neurodegenerative diseases, through a collaboration that could generate more than $1.1 billion-plus for Voyager, the companies said today.
The collaboration is intended to create one-time treatments by combining AbbVie's monoclonal antibody expertise, global clinical development and commercial capabilities with Voyager's gene therapy platform. That platform is designed to generate adeno-associated viral (AAV) vectors that deliver monoclonal antibodies directed against accumulations of tau protein within the brain associated with impaired brain function and neuronal cell loss.
“Voyager's vectorized antibody platform presents an innovative approach to addressing challenges in treating neurological disorders associated with the administration of biologic therapies,” Jim Sullivan, Ph.D., VP, pharmaceutical discovery, AbbVie, said in a statement. “This collaboration has the potential to address the needs of patients who live with conditions such as Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia.”
Neuroscience is one of AbbVie’s four primary areas of therapeutic interest; the other three are immunology, oncology, and virology.
Within neuroscience, developers have long struggled to create successful new drugs for Alzheimer’s. Only a handful of drug successes have ever reached the market, and even they have merely slowed progression of symptoms by 6 to 12 months.
In the most recently-announced failure, Merck & Co. on February 13 halted the Phase III “protocol 019” or APECS study assessing evaluating its verubecestat (MK-8931), a small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), in people with prodromal Alzheimer’s disease. The halt followed a recommendation of the trial’s external Data Monitoring Committee (eDMC), which concluded during a recent interim safety analysis that it was unlikely that positive benefit/risk could be established if the trial continued.
The following day, Biogen’s share price fell 7% following an investor selloff touched by fears of another Alzheimer’s failure. Biogen disclosed February 14 that it made mid-study changes to a pair of Phase III trials for aducanumab (BIIB037), the anti-amyloid beta (Aβ) antibody it is co-developing with Eisai—such as increasing the sample size by more than 500 patients. Data from those studies is expected next year.
A 2014 Cleveland Clinic study found a 99.6% failure rate of clinical trials for Alzheimer's drug candidates between 2002 and 2012. That study found high attrition rates for Alzheimer’s treatments, with 72% of agents failing in Phase I, 92% failing in Phase II, and 98% failing in Phase III.
Voyager reasons that since the cells targeted in the central nervous system (CNS) are long-lived, non-dividing neurons, treatments delivered in a single dose could generate long-lasting, or even lifelong, benefits. Such treatments, the company adds, could likely avoid the limitations associated with weekly or biweekly infusions of biologic therapies for neurodegenerative diseases, such as the small amount of drug able to make its way into the brain.
The company’s founders include co-discoverers of many of the known naturally-occurring AAV capsids, and co-creators of genetically engineered AAV capsids. Voyager says its research efforts include the genetic engineering of capsids to yield vectors with enhanced tissue specificity and improved delivery of genes to the brain and spinal cord.
Voyager says it is also working to optimize novel AAV capsids that demonstrate enhanced blood-brain barrier penetration for the potential treatment of CNS diseases following systemic administration of the AAV gene therapy vector.
“This collaboration also represents an important advance in our strategy to leverage our AAV gene therapy platform and programs through partnerships with biopharmaceutical companies that bring complementary expertise and capabilities, in addition to capital,” added Voyager President and CEO Steven Paul, M.D.
AbbVie agreed to pay Voyager $69 million upfront and up to $155 million in preclinical and Phase 1 option payments. AbbVie also agreed to pay Voyager up to $895 million in payments tied to achieving development and regulatory milestones for each vectorized tau antibody compound.
According to a regulatory filing, AbbVie and Voyager will each identify up to five antibodies for inclusion in the collaboration, then agree to select up to three antibodies as candidates. The value of the partnership could escalate to $1.934 billion-plus royalties if all three candidates are for Alzheimer's indications, or to $1.179 billion for one Alzheimer's candidate and two non-Alzheimer's candidates.
In return for the payments from AbbVie, Voyager agreed to perform research and preclinical development of vectorized antibodies directed against tau, after which AbbVie may select one or more vectorized antibodies to proceed into IND-enabling studies and clinical development. Voyager will oversee the research, IND-enabling and Phase I studies activities and costs.
Following completion of Phase I clinical development, AbbVie has an option to license the vectorized tau antibody program, and would then lead further clinical development and global commercialization for tauopathies, including Alzheimer's disease and other neurodegenerative diseases.
Voyager is also eligible to receive tiered royalties on global commercial net sales of vectorized antibodies for tauopathies—and has an option to share in the costs of clinical development for higher royalty rates.