Biogen, Denali pull Parkinson's drug after failed trial

Biogen has stopped development of Denali-partnered Parkinson's disease candidate BIIB122, after it failed to move the needle in a phase 2b trial.

There were already signs of diminished confidence in BIIB122, a small-molecule inhibitor of LRRK2, when Biogen and Denali decided to abandon a large-scale, expensive phase 3 study (LIGHTHOUSE) in patients with Parkinson's associated with LRRK2 mutations three years ago, which was not expected to generate results until 2031.

The two partners devoted their energies instead to LUMA, a smaller phase 2b that had an earlier readout and recruited both LRRK2-mutated and wild-type patients, but now that has turned out to be a bust.

Biogen and Denali have now confirmed that the results show BIIB122 (also known as DNL151) did not slow the progression of Parkinson's compared to placebo, as measured by the MDS-UPDRS rating scale, and also missed secondary endpoints, even though biomarker testing suggested it was reducing LRRK2 kinase activity by around 30%.

The drug will be discontinued in idiopathic Parkinson's, but Denali is independently continuing a phase 2a study, called BEACON, that is focusing specifically on Parkinson's patients with specific LRRK2 pathogenic mutations.

Biogen bought into Denali's LRRK2 programme in a deal potentially worth more than $2.1 billion in 2020, claiming co-development and co-marketing rights to a group of LRRK2-targeted small-molecule drugs, headed by BIIB122, which at the time was in early-stage clinical testing.

"While we are disappointed with these results, we believe the LUMA study was a robust test of LRRK2 inhibition using BIIB122 in idiopathic Parkinson's disease and there is more to be learned about LRRK2 as a potential therapeutic target," said Denali's chief medical officer, Peter Chin.

"We look forward to further analysis of the LUMA data and the results from BEACON to inform next steps for development," he added.

The rationale for BIIB812's development was that LRRK2 regulates lysosomes, which play a vital role in cell function by breaking down excess or worn-out cell parts. The functioning of lysosomes is impaired in Parkinson's, leading to speculation that this may contribute to the neurodegeneration that characterises the disease.

The disappointing LUMA result is a red flag for other companies working on LRRK2 inhibitors for Parkinson's.

That includes Neuron23, which raised $96.5 million in financing last year to fund its ongoing phase 2 NEULARK trial of NEU-411 in early-stage, LRRK2-driven Parkinson's, and Oncodesign Precision Medicine, which was awarded almost $7 million in funding in March from The Michael J. Fox Foundation to support a phase 1b study of its OPM-201 candidate that is due to start next year. Montara Therapeutics, meanwhile, has a programme in preclinical development.

OPM-201 was previously partnered with Servier, but the pharma group returned rights to the programme in 2024, despite positive phase 1 results. Another former partner, Ipsen, also decided not to pursue its interest.