Low Dose Combination of Extended-Release Pramipexole and Rasagiline Shows Comparable Efficacy to Pramipexole Alone, With Greater Safety

Lawrence Elmer, MD, PhD

Exploratory findings from a phase 3 randomized, controlled trial (NCT03329508) assessing P2B001 (Pharma Two B), a low dose combination of extended-release pramipexole and rasagiline, in Parkinson disease (PD) showed efficacy that was comparable to extended-release pramipexole (Prami-ER) alone, but with reduced sleep-related and dopaminergic adverse events (AEs). Pharma Two B plans to submit a new drug application for P2B001 to the FDA in 2023.

At the end of a 12-week treatment period, changes in Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and III scores combined were between P2B001 and Prami-ER were not significantly different (–8.35 [±0.86] vs 7.98 [±0.6]), with noninferiority confirmed in post-hoc analysis (margin of 3 points; P = .0052). Presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, the data revealed no significant between-group differences in UPDRS Part II (activities of daily living) or Part III (motor) scores.

Led by Lawrence Elmer, MD, PhD, medical director, Center for Neurological Disorders, University of Toledo, the double-blind, parallel-group trial featured patients with early untreated PD with less than 3 years from diagnosis and not on anti-parkinsonian therapy. The therapy in question, P2B001, is a once-daily combination of ER formulations of 0.6-mg pramipexole, a dopamine agonist, and 0.75-mg rasagiline, a monoamine oxidase type B (MAO-B) inhibitor.

"The results of this Phase 3 trial represent positive news for newly diagnosed PD patients, as there has been a clear unmet need for an initial, once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sedation compared to pramipexole monotherapy," Elmer said in a statement. "As a clinician caring for PD patients, I know the side effects from dopamine agonists as monotherapy for early PD may be challenging and often limit treatment options, especially for younger people who may be required to drive for their employment and also for older people who often cannot tolerate DA side effects, including excessive daytime somnolence."

READ MORE: Promising Disease-Modifying Therapies in Parkinson Disease

Additional findings from the analysis showed similar rates of at least a 4-point improvement in UPDRS total scores, with 74.1% and 76.6% of patients on P2B001 and Prami-ER, respectively, achieving this (OR, 0.87; 95% CI, 0.44-1.75; P = .70). Ultimately, patients treated with P2B001 reported significant reductions of 7.98 points (SE, 0.60) in UPDRS total score compared with reductions of 5.32 points (SE, 0.61; treatment difference, –2.66; 95% CI, –4.33 to –1.00]; P = .0018) and 4.69 points (SE, 0.61; treatment difference, –3.30; 95% CI, –4.96 to –1.63; P = .0001) observed with its active ingredients.

In terms of safety, treatment-emergent AEs were recorded in 74.7% of patients on P2B001 vs 86.5% of those on titrated Prami-ER. Other safety measures favored P2B001, including lower frequency of dopaminergic-related TEAEs (44.7% vs 66.2%), somnolence (14.7% vs 31.3%) and orthostatic hypotension (2.7% vs 12.2%).

In the original study, 519 untreated individuals with PD were randomized in a 2:2:2:1 fashion for 12 weeks of treatment with either P2B001 (n = 150) pramipexole 0.6 (n = 148), rasagiline 0.75 mg (n = 147), or marketed titrated pramipexole-ER (n = 74). In total, 90% to 93% of each group completed the full 12 weeks. In addition to demonstrating similar efficacy, treatment with P2B001 was associated with significantly less daytime sleepiness, as measured by Epworth Sleepiness Scale (ESS) scores by a mean change from baseline in of –0.33 (SE, 0.25) for P2B001, compared with 2.33 (SE, 0.36) for ER pramipexole (treatment difference, –2.66; 95% CI, 3.50 to –1.81; P <.0001).³

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REFERENCES
1. Pharma Two B to present additional positive results from P2B001 phase 3 trial at 2023 American Academy of Neurology Annual Meeting. News release. Pharma Two B. April 23, 2023. Accessed April 23, 2023. https://www.globenewswire.com/news-release/2023/04/23/2652313/0/en/Pharma-Two-B-to-Present-Additional-Positive-Results-from-P2B001-Phase-3-Trial-at-2023-American-Academy-of-Neurology-Annual-Meeting.html
2. Elmber L, Litman P, Friedman H, Fitzer-Attas C, Oren S. P2B001 (low dose combination of extended-release pramipexole and rasagiline) versus titrated extended-release pramipexole in the management of early Parkinon’s disease: exploratory findings from a randomized, controlled trial. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstact 003733
3. Pharma Two B announces positive topline results from its pivotal phase 3 study of P2B001 in early Parkinson disease. News release. Pharma Two B. December 15, 2021. Accessed April 23, 2023. https://www.biospace.com/article/pharma-two-b-announces-positive-topline-results-from-its-pivotal-phase-iii-study-of-p2b001-in-parkinson-s-disease/