Anxious for actionable data sooner than 2031, Biogen trims Denali-partnered Parkinson's program

Biogen and partner biotech Denali Therapeutics are trimming down a Parkinson’s disease clinical program that was not expected to complete until 2031 in hopes of getting some actionable data sooner.

As Biogen goes through an R&D reprioritization, the decision has been made to revise the program for BIIB122, a small-molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2), according to a Monday press release

Biogen had previously planned to conduct a phase 2b study called LUMA for early-stage Parkinson’s and a phase 3 called LIGHTHOUSE specific to the LRRK2 mutation. LUMA kicked off in May 2022, and LIGHTHOUSE started in September 2022.

Now, Biogen is discontinuing the LIGHTHOUSE study due to its complexity and long timeline—which had an end date in 2031. Instead, focus will shift to securing “a timely readout” for LUMA and collecting data on LRRK2 mutations within that trial. Therefore, Biogen and Denali will amend the LUMA protocol to include eligible patients with a LRRK2 genetic mutation while continuing to enroll early-stage patients. Patients who had already been enrolled in LIGHTHOUSE will be given the opportunity to join LUMA instead.

The LIGHTHOUSE study had been expected to enroll 400 participants, while LUMA had space for 640, according to the clinical trials database. Denali said that 640 remains the target number for LUMA, which is expected to serve as registration-enabling for BIIB122.

“Including both patient populations in the LUMA study is expected to answer the question of whether LRRK2 inhibition is a viable treatment approach for early-stage Parkinson’s disease and to provide initial data in Parkinson’s disease related to LRRK2 mutations sooner than would have been possible with the LIGHTHOUSE study,” Denali said in a Securities and Exchange Commission filing. Data from LUMA will then inform future development plans.

Both companies said in separate statements that they remain committed to the development of small-molecule LRRK2 inhibitors. The two signed a deal in 2020 worth $1 billion upfront and a further $1.125 billion in milestones later on to develop these therapies, which resulted in BIIB122.

Biogen's new CEO Christopher Viehbacher has promised an overhaul of the R&D program and an assessment of how risky assets are managed. The company knows a thing or two about taking big bets with its neurodegeneration focus; see the controversy and triumph surrounding Eisai-partnered Alzheimer's meds Aduhelm and Leqembi