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First Patient Treated in Phase 2a Trial of Investigational BIIB122 for LRRK2-Associated Parkinson Disease
Key Takeaways
- Denali Therapeutics has initiated the phase 2a BEACON study to evaluate BIIB122 in LRRK2-associated Parkinson's disease, focusing on safety and biomarkers.
- The phase 2b LUMA study is assessing BIIB122 in early-stage Parkinson's disease, with or without LRRK2 mutations, using MDS-UPDRS for symptom evaluation.
BIIB122 is a selective, central nervous system-penetrant small molecule that could potentially improve lysosomal dysfunction among patients with LRRK2-associated Parkinson disease.
Carole Ho, MD
(Credit: Denali)
According to a recent company update, Denali Therapeutics has announced the start of dosing in the global phase 2a BEACON study (NCT06602193) assessing the investigational drug leucine-rich repeat kinase 2 (LRRK2) inhibitor BIIB122 (DNL151) among patients with LRRK2-associated Parkinson disease (LRRK2-PD).1 LRRK2 inhibition offers a potential therapeutic strategy to slow PD progression by addressing lysosomal dysfunction involved in the disease's pathology.
In BEACON, researchers will investigate the safety and biomarkers associated with oral daily dosing of BIIB122 in approximately 50 patients with PD and LRRK2 pathogenic mutations confirmed by genetic testing. The trial is designed to enroll patients into a double-blind treatment period of 3 months followed by an open label extension. BIIB122 is also being assessed in the ongoing global phase 2b LUMA study (NCT05348785), in collaboration with Biogen, among patients with early-stage PD with or without a LRRK2 mutation.2
“We are thrilled to initiate this study and broaden our efforts in evaluating BIIB122 as a potential treatment for people living with Parkinson’s disease related to LRRK2 mutations,” Carole Ho, MD, chief medical officer at Denali, said in a statement.1 “We look forward to continued collaboration with the Parkinson’s community as we aim to generate biomarker and safety data to inform how LRRK2 inhibition may have an impact on the course of this disease.”
LUMA is a double-blind, placebo-controlled study that aimed to include 640 participants between the ages of 30 and 80 years with early-stage PD. They are randomly assigned to either 225 mg of oral BIIB122 or placebo once daily for a minimum of 48 weeks and a maximum of 144 weeks. To understand whether BIIB122 slows the worsening of symptoms, investigators are evaluating patients on Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts 2 and 3.
READ MORE: Brenig Therapeutics Initiates First-in-Human Trial of LRRK2 Inhibitor BT-267 for Parkinson Disease
In addition to MDS-UPDRS, other outcomes investigators will key in on include treatment-emergent adverse events (AEs) and serious AEs, and time to confirmed worsening in Schwab and England Activities of Daily Living Scale (SEADL). The SEADL scale reflects the speed, ease, and independence with which an individual performs daily activities or personal chores with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence.
“LRRK2 continues to be a prominent target in Parkinson’s research, and a priority area of focus for disease-modifying therapies,” Todd Sherer, PhD, chief mission officer at The Michael J. Fox Foundation, said in a statement.1 “The Phase 2a study of BIIB122 is a meaningful milestone in advancing the potential of LRRK2 as a therapeutic approach for people with Parkinson’s disease.”
In June 2023, Biogen and Denali discontinued a portion of the clinical development program for BIIB122 known as the phase 3 LIGHTHOUSE study (NCT05418673), which was initiated in September 2022. The companies noted in the announcement that the decision was made “in consideration of the LIGHTHOUSE study’s complexity including the long timeline with anticipated study completion in 2031.” They added that the modifications were not because of safety or efficacy data from studies of the treatment and that they “remain committed to advancing the development of BIIB122.”3
