Closely watched Parkinson's drug from Biogen and Denali fails key clinical trial
Biogen and Denali Therapeutics announced on Wednesday in a joint release that their LRRK2 inhibitor BIIB122 (generic name: tolinapant) had failed the primary endpoint of the Phase 3 LUMA clinical trial. The study, which enrolled 712 patients diagnosed with early Parkinson's disease, did not demonstrate a statistically significant difference compared with placebo in MDS-UPDRS motor score progression at 96 weeks.
The LUMA trial had been framed as a rare symbol of hope when it launched in 2022. BIIB122 targeted patients whose Parkinson's was driven by LRRK2 (Leucine-Rich Repeat Kinase 2) gene mutations, in addition to the broader idiopathic Parkinson's population (roughly one-third of whom also display LRRK2 pathway hyperactivity).
Priya Singhal, Biogen's head of research and development, told STAT News in a written statement that 'every clinical failure is first a loss for patients; yet we have generated a substantial dataset'. Singhal said the study results would be published in peer-reviewed journals in the coming months and shared with scientists across the LRRK2 pathway biology community.
Some secondary endpoints showed positive signals. In a subgroup of 142 trial participants who carried the LRRK2 G2019S mutation, the BIIB122 arm recorded a 23 per cent slowing in motor progression at 14 months. This suggests a possible role for the drug in patients with specific genetic backgrounds; however, the company said it would not be filing for approval based on subgroup analysis.
The financial market reaction was sharp. Biogen shares opened Wednesday 21 May down 18 per cent, falling from 187.40 dollars to 153.68; Denali Therapeutics shares lost 34 per cent. Goldman Sachs pharmaceutical industry analyst Salveen Richter said in a client note that 'BIIB122's annual peak-sales potential had previously been modelled at 3.4 billion dollars; that figure is now expected to be revised to 0.4 billion'.
The research community focused on LRRK2 has reacted with mixed signals. Dr Brian Fiske, head of research at the Michael J. Fox Foundation, told STAT that 'the LUMA failure is not a structural turning point; on the contrary, it requires us to rethink our measurement tools in clinical design'. Fiske referred to the literature that has accumulated over the past three years on the tendency of the MDS-UPDRS score to plateau in early Parkinson's.
On the Denali side, co-founder and chief executive Ryan Watts confirmed the drug candidate would be re-evaluated for another neurodegenerative indication. 'We are actively reviewing BIIB122's early-stage opportunities in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia,' he said. Watts noted the company's 2.8 billion dollar cash position will guarantee 'that the new drugs in our pipeline remain in clinical development through the next decade'.
The clinical research community will now turn its attention to competing parallel programmes. Vanqua Bio, AbbVie and Cerevel Therapeutics (acquired by AbbVie in 2024 for 8.7 billion dollars) all carry LRRK2 programmes that will need to learn from BIIB122's failure. Vanqua Bio chief executive Sam Whelan told Reuters that 'we test agents with different molecular profiles,' emphasising that the field's plurality is preserved.
Patient communities responded with a more emotional reaction. Katherine Crawford, senior policy manager at Parkinson's UK, told the BBC that 'each clinical failure condemns our patients to another decade of delay'. Crawford said the organisation will request an additional 50 million pounds in annual investment in Parkinson's basic research from the UK Medical Research Council.
Parkinson's disease affects approximately 8.5 million people worldwide and remains a neurodegenerative condition without a cure. Although this article presents medical information, individual patients' treatment options should always be discussed with their treating physician; clinical trial results are designed for the general population and do not replace personal health decisions.