BIIB122 Discontinued in LRRK2 Parkinson Disease, Pimavanserin and PTSD-Associated Insomnia, Obstructive Sleep Apnea Following VNS

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Biogen and Denali have announced that they are discontinuing a portion of the clinical development program for BIIB122 (also known as DNL151), an investigational small molecule inhibitor of LRRK2 in development for the treatment of Parkinson disease (PD). As a result of this decision, the phase 3 LIGHTHOUSE study (NCT05418673), which was initiated in September 2022, will be terminated. The companies are choosing to refocus their efforts “to enable a timely readout on efficacy in early-stage idiopathic Parkinson's disease while gaining further clinical data in Parkinson’s disease with and without an LRRK2 mutation.” Those patients with PD related to LRRK2 mutations who were enrolled in the now discontinued program will be offered an opportunity to join the ongoing phase 2b LUMA study (NCT05348785), which began in May 2022.

A trial presented at the 2023 SLEEP Annual Meeting, held June 3-7, in Indianapolis, Indiana, demonstrated feasibility and potential benefits of pimavanserin (Nuplazid; Acadia Pharmaceuticals) in the treatment of post-traumatic stress disorder (PTSD)-associated insomnia. A larger, randomized trial is needed to further confirm these benefits. Led by Laura Marsh, MD, Menninger Department of Psychiatry, Baylor College of Medicine, the pilot, open-label trial (NCT04188392) featured 6 adult veterans with chronic insomnia disorder and PTSD assessed over a period of 6 weeks. Participants completed 7 days of actigraphy monitoring and 2 consecutive in-lab polysomnograms pre-treatment. Primary outcomes were recruitment and retention rates, defined as the total number of individuals recruited into treatment and treatment completion rates, with a goal of 75% completion.

Findings from a meta-analysis of 10 studies showed that obstructive sleep apnea (OSA) is a common adverse event following vagus nerve stimulation (VNS), with no differences based on sex. Investigators concluded that routine screening for OSA following VNS implantation may be a reasonable choice. Prior research has suggested that VNS can cause an increase in respiratory rate, decrease in respiratory amplitude, decrease in tidal volume, and decrease in oxygen saturation during periods of device activation. pooled rates of OSA in the meta-analysis, which comprised of 7 retrospective and 3 prospective studies totaling 306 patients, were 27.3% (95% CI, 15.1-41.5).

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