Biogen and Denali Therapeutics announced that their Parkinson’s disease drug candidate failed to meet the primary endpoint of a phase 2b trial, and the companies have decided to discontinue development of the therapy for the idiopathic form of the disease.
In 2020, Biogen spent $400 million on a partnership with Denali to develop an LRRK2 inhibitor. The wager was based on the evidence that LRRK2 is involved in Parkinson’s disease: mutations that activate the kinase are associated with the accumulation of toxic proteins. In 2022, Biogen started a phase 2 trial in early-stage Parkinson’s and began a phase 3 study in a genetic subpopulation.
Biogen was forced to backpedal on the phase 3 trial by scrapping it after enrolling seven patients, but continued with the 650-patient midphase trial and posted results after the stock markets closed Thursday. The analysts viewed the study as a risky prospect, and the William Blair side had modeled a 10% chance of the program’s success for Denali.
BIIB122 (also known as DNL151) didn’t slow the progression of Parkinson’s as much as placebo – meaning the trial didn’t meet its primary endpoint. Biogen said it achieved over 90% kinase inhibition in the periphery, and a decrease in a CSF biomarker of kinase activity of about 30%. The concentration of the molecule in the blood and CSF was within normal limits.
However, this indication of target activity did not translate to any positive effects in terms of outcomes, with secondary endpoints also showing no positive impact of BIIB122. Overall, the drug candidate was well tolerated with an acceptable safety profile, the partners said, but the lack of efficacy signals led the companies to discontinue development of BIIB122 in idiopathic Parkinson’s.
Denali will continue to conduct the small molecule as a stand-alone clinical trial in a phase 2a study to enroll individuals with LRRK2-related Parkinson’s. The estimated primary completion date, according to the federal trials database, for the 12-week, 50-patient trial was late last month. The phase 2a data, along with the failure of the trial, will help guide the next steps in development, said Peter Chin, M.D., Denali’s Chief Medical Officer, in a statement.
The failure of the study with the target activity is a positive development for William Blair analysts, who said they are “encouraged to see Denali continue the phase 2a trial to further explore the LRRK2 dysfunction thesis.” LRRK2 mutations are responsible for approximately 4% of familial and 1-2% of sporadic Parkinson’s cases.
Biogen axed an Ionis-partnered antisense oligonucleotide that targets LRRK2 last year. Other biotechs are moving forward with the work, too: Neuron23 is enrolling people with early Parkinson’s disease into a phase 2 study of its LRRK2 inhibitor, while Arvinas is advancing a PROTAC in progressive supranuclear palsy (PSP).
Biogen has announced the discontinuation of its collaborative development program with Denali Therapeutics after a Phase 2 clinical trial failed to meet its primary objectives. The decision represents a significant setback for efforts to develop new therapies targeting Parkinson’s disease, a progressive neurological disorder affecting millions of people worldwide.
Biogen and Denali Part Ways Following Clinical Setback
A promising neuroscience collaboration has come to an end after an investigational therapy failed to produce the desired results in a mid-stage clinical trial. The outcome prompted the companies to discontinue development of the program, underscoring the challenges associated with developing treatments for complex neurodegenerative disorders.
Trial Results Prompt Strategic Reassessment
The Phase 2 study was designed to evaluate the safety and effectiveness of the experimental therapy in patients with a progressive neurological condition. Despite earlier optimism, the treatment did not demonstrate sufficient clinical benefit compared with expectations. Following a detailed review of the data, both organizations concluded that continued investment in the program was not justified.
Parkinson’s Program Falls Short in Phase 2 Testing
The Phase 2 study was designed to evaluate whether the investigational treatment could slow disease progression or improve symptoms associated with Parkinson’s. However, the trial did not achieve the expected outcomes, leading Biogen and Denali to reassess the future of the program. As a result, further development efforts related to this specific Parkinson’s therapy have been halted.
Financial and Strategic Implications
The termination of the program allows both companies to focus resources on other pipeline candidates with stronger development potential. Strategic decisions of this nature are common within the biopharmaceutical industry, where organizations must continually evaluate scientific evidence and allocate capital to the most promising opportunities.
Industry Impact
The setback serves as a reminder of the high risks involved in drug development, particularly in neuroscience. Even therapies backed by strong scientific rationale can fail to deliver positive clinical outcomes. However, each trial contributes valuable information that helps researchers refine future approaches and improve understanding of disease biology.Parkinson’s
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