An open-label phase 2b trial assessing ND0612 showed that the rate of treatment responders increased over a 12-month period among patients with Parkinson disease who experienced motor fluctuation.
Aaron L. Ellenbogen, DO, MPH, FACN
(Credit: MIND)
New preliminary findings in a responder-analysis from the ongoing open-label phase 2b BeyoND trial (NCT02726386) assessing ND0612 (NeuroDerm), a 24-hour/day subcutaneous infusion of liquid levodopa/carbidopa (LD/CD), showed a reduction in OFF time at 12 months among patients with Parkinson disease (PD) who experience motor fluctuations, supporting the efficacy of the treatment in this patient population.1
In the analysis, investigators identified 44% of patients (n = 214) as treatment responders, using the last observation carried forward, and reported that this level of response was maintained over 12 months of follow-up. Notably, researchers also noted that at 12 months 63.5% of patients achieved at least a 25% reduction in OFF time from baseline and 26.9% of patients achieved at least a 75% reduction in OFF time.
These results were presented at the 3rd Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 22-25, 2024, in Washington, DC, by lead author Aaron L. Ellenbogen, DO, MPH, FACN, neurologist and movement disorder specialist at Michigan Institute for Neurological Disorders. Participants in the BeyoND trial were diagnosed with PD, had at least a Hoehn & Yahr score of 3 during ON, and experienced at least 2 hours of daily OFF time. In the performed analysis of daily OFF time, as recorded by patient home diaries, investigators defined a responder conservatively as a patient that achieved at least 50% reduction from baseline in adjusted mean daily OFF time.
Additional findings showed that 12.8% of patients achieved a 100% OFF time reduction with the treatment at 12 months. Using only observed cases, excluding the last observation carried forward, investigators reported that the rate of ND0612 treatment responders increased from 44.0% at month 1 (n = 150) to 53.3% at month 6 (n = 107), and 56.7% at month 12 (n = 90). Previous findings with ND0612 at 1 year revealed a favorable safety and tolerability profile. Further prior results showed that the adjusted mean daily ‘Good ON’ time, which is the sum of ON time without dyskinesia plus ON time with non-troublesome dyskinesia, increased from baseline by 2.3 hours at month 3 and maintained for at least 12 months.
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Earlier this month, the FDA issued a complete response letter (CRL) to NeuroDerm for its submission of ND0612 as a potential treatment for ON time in PD. Mitsubishi Tanabe Pharma and its wholly owned subsidiary, NeuroDerm, noted that they are reviewing the CRL and will work closely with the FDA to address its comments to consider the future direction.2
ND0612’s application was supported by data from the phase 3 BouNDless trial (NCT04006210), a double-blind, double-dummy, active-controlled trial that featured 259 patients with PD who experienced at least 2.5 h/day of OFF time. In the study, treatment with the investigational agent resulted in an additional 1.72 h (95% CI, 1.08-2.36) of ON time without troublesome dyskinesia compared with oral LD/CD (change, –0.48 h; 95% CI, –0.94 to –0.02; P <.0001).3
The study, published earlier this year in The Lancet Neurology, met its primary end point and first 4 secondary end points as well. Of the 9 prespecified hierarchical outcomes, significant treatment differences favoring subcutaneous ND0612 included daily OFF time (–1.40; 95% CI, –1.99 to –0.80), Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)-II scores (–3.05; 95% CI, –4.28 to –1.81), Patients Global Impression of Change (OR, 5.31; 95% CI, 2.67-10.58), and Clinical Global Impression of Improvement (OR, 7.23; 95% CI, 3.57-14.64). Of note, hierarchical testing ended after the 4th secondary end point.
Of those randomized, 94% (n = 243) completed the study, where they continued on into the open-label extension. Throughout the open-label optimization and double-blind phase, most patients experienced at least 1 adverse event (AE) while on ND0162. Infusion site reactions, most of which were mild, were the most commonly reported AE (open-label ND0612: 83%; ND0612 double-blind: 57%; oral LD/CD: 43%). There were 7 reported serious AEs found in 4 patients, which included infusion-site cellulitis (n = 2), infusion-site abscess and infusion-site ulcer (n = 1), and parasthesia and peripheral sensorimotor neuropathy (n = 1).
During BouNDless, a relatively small number of patients discontinued therapy in both groups, 5.5% (n = 7) in the ND0612 and 3.1% (n = 4) in the immediate-release LD/CD group, The rates of AEs were similar, with 80.5% (n = 103) of those in the ND0612 group reporting AEs compared with 74% (n = 97) of those in the immediate-release LD/CD group.
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