Biogen and Denali halt BIIB122 trial for idiopathic Parkinson’s
Treatment failed to slow early-stage disease progression in Phase 2b trial
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- Biogen and Denali have discontinued the testing of BIIB122 for idiopathic Parkinson's disease.
- The LRRK2 inhibitor failed to slow disease progression in early-stage patients.
- Denali continues a separate study for Parkinson's patients with LRRK2 gene mutations.
Biogen and Denali Therapeutics have ended their clinical development of BIIB122 for people with idiopathic Parkinson’s disease after the experimental therapy failed to slow disease progression in a Phase 2b trial.
The decision follows results from the Phase 2b LUMA study (NCT05348785), which compared BIIB122 (also known as DNL151) against a placebo in adults with early-stage Parkinson’s. The drug, designed as an LRRK2 inhibitor, did not show a statistically significant benefit in delaying disease worsening.
While the joint effort for idiopathic (of unknown cause) Parkinson’s has been halted, Denali will independently continue a separate Phase 2a study called BEACON (NCT06602193). This smaller trial focuses specifically on patients who carry LRRK2 gene mutations known to be associated with Parkinson’s disease. Data from the BEACON study is anticipated in the first half of 2027.
Continuing the search for answers
“While these are not the results we hoped for, these data provide important information to the Parkinson’s community and will be presented at an upcoming scientific conference,” Diana Gallagher, MD, senior vice president and head of neurodegeneration clinical development at Biogen, said in a company press release. “We are profoundly grateful to the patients, families, and investigators who participated in this study and contributed to our understanding of Parkinson’s disease.”
Mutations in the LRRK2 gene are among the most common genetic causes of Parkinson’s. These mutations are generally linked to an overactivation of protein leucine-rich repeat kinase 2 (LRRK2), which may impair lysosomal function and contribute to neurodegeneration. Lysosomes are cellular compartments responsible for recycling unwanted or damaged molecules. However, Parkinson’s patients without these mutations also show higher LRRK2 activity.
BIIB122 is designed to enter the central nervous system, meaning the brain and the spinal cord, and inhibit LRRK2 to restore the recycling activity of lysosomes. Researchers hoped this mechanism would ease Parkinson’s symptoms and slow disease progression.
In a Phase 1 trial (NCT04557800) evaluating BIIB122 in healthy volunteers, the treatment reduced LRRK2 activity and biomarkers of LRRK2 activity, such as phosphorylated Rab10. It was also well tolerated, with no serious side effects reported.
Similar results were reported in a Phase 1b trial (NCT04056689) enrolling 36 Parkinson’s patients, who were randomly assigned to receive BIIB122 or a placebo once daily for 28 days.
The larger LUMA trial evaluated the safety and efficacy of BIIB122 in 648 people with early-stage Parkinson’s disease who were 30 to 80 years of age. The group included participants with and without a disease-causing LRRK2 variant. Participants were randomly assigned to receive BIIB122 or a placebo for a period ranging from about one year to more than two years.
The trial failed to meet its primary goal of slowing disease progression compared with the placebo. This goal was assessed as the time to confirmed worsening in the combined score of modified Movement Disorder Society Unified Parkinson’s Disease Rating Scale parts 2 and 3, which measure Parkinson’s motor symptoms.
Secondary endpoints, which included changes from baseline in nonmotor symptoms as well as motor symptoms, also failed to show beneficial effects. However, exploratory biomarker endpoints confirmed that BIIB122 successfully inhibited LRRK2 activity in blood and cerebrospinal fluid, which surrounds the brain and spinal cord.
“While we are disappointed with these results, we believe … there is more to be learned about LRRK2 as a potential therapeutic target,” said Peter Chin, MD, Denali’s chief medical officer and head of development. “Independently, we continue to study this small molecule inhibitor in the Phase 2a BEACON study … and look forward to further analysis of the LUMA data and the results from BEACON to inform next steps for development.”
The ongoing BEACON study is assessing the safety, pharmacological properties, and biomarkers of lysosomal pathway engagement in 50 adults 30 years or older with confirmed LRRK2 mutations. Participants in that trial were randomly assigned to receive BIIB122 at a 225 mg dose or a placebo once daily for three months.
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