Voyager Therapeutics is losing Neurocrine Biosciences as a research partner on an experimental Parkinson’s disease treatment, the latest in a string of setbacks for the biotech’s efforts to develop gene therapies addressing neurological disorders.
Cambridge, Massachusetts-based Voyager disclosed late Tuesday that Neurocrine provided a termination notice on the Parkinson’s candidate NBlb-1817, which is currently in mid-stage clinical testing. The decision follows the FDA’s December decision to place a clinical hold on that program due to safety concerns.
Termination of the partnership on the Parkinson’s gene therapy will be effective Aug. 2. The collaboration agreement requires Neurocrine to provide 180 days written notice of a termination. The San Diego biotech acknowledged providing that notice in its own regulatory filing. Three other programs covered by the agreement, one for Friedreich’s ataxia and two others in the discovery stage, are not affected by Tuesday’s decision and will continue, Voyager said.
The alliance began in 2019 when San Diego-based Neurocrine pledged $165 million in cash and stock to Voyager. Of the four programs covered by the pact, the Parkinson’s candidate was the most advanced. According to the deal terms, Neurocrine was responsible for funding Phase 2 clinical development. After the study produced data, Voyager held the option to split the rights to the gene therapy with Neurocrine, sharing in further development costs. Alternatively, Voyager could grant its partner full global rights in exchange for milestone payments pegged to sales.
Prior to the Covid-19 pandemic, Neurocrine anticipated advancing the Parkinson’s gene therapy to a pivotal study in the second half of 2020, the company said in its annual report. The pandemic and the clinical hold stalled that timeline.
Voyager uses engineered viruses to deliver gene therapies to the brain. Parkinson’s is characterized by a lack of dopamine, a brain chemical that’s key to controlling muscle movement. Standard treatment includes prescriptions of levodopa, which is converted by a brain enzyme into dopamine.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
As Parkinson’s progresses, a patient has less of that key enzyme in parts of the brain where it is needed to convert levodopa to dopamine, Voyager states in its filings. The Parkinson’s candidate is designed to deliver a gene directly into the neurons where dopamine receptors are located, providing the instructions the brain needs to make the key enzyme.
The Parkinson’s gene therapy is administered via a direct injection into the brain. For its amyotrophic lateral sclerosis and Friedreich’s ataxia programs, the company is exploring other approaches, including spinal or intravenous injections.
In its announcement of the end of the partnership in Parkinson’s, Voyager said Neurocine based its decision on a review of its portfolio and the prioritization of other programs in its pipeline. No mention was made about the safety of the Parkinson’s gene therapy. When Voyager disclosed the clinical hold in December, it said that a Neurocrine safety report noted MRI abnormalities in some study participants. It also said the independent board responsible for monitoring the safety of study participants requested a pause on dosing of patients until it could review additional data.
Until the alliance on NBIb-1817 is officially terminated in August, Neurocrine is the company of record for the clinical program. Voyager said that last month, the FDA informed Neurocrine of the information needed to respond to the clinical hold. In addition to an assessment of how the therapy may have contributed to the adverse findings, Voyager said the agency wants a mitigation plan to manage them along with supportive data to justify that the benefit of the therapy outweighs its risks.
Voyager said it will support Neurocrine on any imaging or clinical assessments requested by data safety monitors of the study, as well as any information sought by the FDA. The company added that it is evaluating the financial effect the termination will have on the company and the future of the Parkinson’s program.
The end of the partnership on the Parkinson’s gene therapy marks the second time a company has passed up the opportunity to advance that program. Sanofi was Voyager’s first partner on the experimental therapy, committing $100 million up front in 2015 for rights to several gene therapies for brain disorders. At the time of the deal, the Parkinson’s gene therapy was in early-stage testing. In 2017, Sanofi returned the therapy to Voyager after the biotech declined to amend the original deal to grant the pharma giant a share of the U.S. rights to the program.
The loss of Neurocrine as a partner in Parkinson’s comes a little more than six months after an alliance with AbbVie ended. That partnership focused on developing gene therapies for Alzheimer’s and Parkinson’s. AbbVie terminated the alliance before either program reached Phase 1 testing, at which point Voyager would have become eligible for additional payments from the North Chicago, Illinois-based pharma company.
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