Combination Agent P2B001 Shows Promise for Parkinson Disease in Phase 3 Data

C. Warren Olanow, MD

After announcing that its investigational Parkinson disease (PD) therapy P2B001 had met its primary and key secondary end points in December 2021,¹ Pharma Two B has presented efficacy and safety data from its phase 3 trial (NCT03329508) suggesting that the investigational combination therapy is safe and results in significant improvements in Unified Parkinson Disease Rating Scale (UPDRS) total scores.²

The data were presented at the 2022 American Academy of Neurology (AAN) annual meeting in Seattle, Washington, by C. Warren Olanow, MD, professor emeritus, Departments of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai, and CEO, Clintrex Research Corporation. Ultimately, patients treated with P2B001 reported significant reductions of 7.98 points (SE, 0.60) 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.

The investigational therapy is a once-daily combination of extended-release (ER) formulations of 0.6-mg pramipexole, a dopamine agonist, and 0.75-mg rasagiline, a monoamine oxidase type B (MAO-B) inhibitor. The cohort of 519 untreated individuals with a disease duration of less than 3 years, randomized in 2:2:2:1 fashion for 12 weeks of treatment with either P2BB001 (n = 150), pramipexole 0.6 mg (n = 148), rasagiline 0.75 mg (n = n = 147), or marketed titrated pramipexole-ER (n = 74). In total, 90% to 93% of each group completed the full 12 weeks.

“We are very pleased to share the positive data from our well-designed, rigorous, active-controlled phase 3 study of P2B001 with the many neurologists who are attending AAN,” Olanow said in a statement.³ “P2B001 has the potential to become a leading treatment option for patients with Parkinson disease, particularly as firstline therapy for early-stage patients of all ages. If approved, P2B001 will enable patients to be treated with a once-daily effective therapy that requires no titration while minimizing the dopaminergic side effects and daytime sleepiness often seen with this class of drugs.”

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Additionally, P2B001 demonstrated comparable efficacy to ER pramipexole (treatment difference, 0.37; 95% CI, –1.67 to 2.42; P = .71) 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).²

There were also fewer reported dopaminergic adverse events (AEs) associated with P2B001 (44.7%) compared with ER premipexole (66.2%). Those AEs included somnolence (P2B001: 14.7%; pramipexole: 31.1%) and orthostatic hypotension (P2B001: 2.7%; pramipexole: 12.2%).

Pharma Two B noted in its announcement that the data on investigational therapy has been suggestive that the therapy increases striatal dopaminergic transmission through its distinct and possibly synergistic mechanisms, giving P2B001 a possible beneficial efficacy-safety risk ratio for those with PD. Additionally, the company noted that low doses of the combination utilized in P2B001 are not currently available, while ER rasagiline is in a proprietary dosage form.

“We are honored that the positive outcomes from our phase 3 study of P2B001 in early Parkinson’s patients [were] chosen for oral presentation at the AAN annual meeting,” Sheila Oren, MD, MBA, CEO, Pharma Two B, said in a statement.³ “Early Parkinson’s patients need a treatment option that can significantly improve motor symptoms and daily function, while avoiding side effects, such as daytime sleepiness, orthostatic hypotension, and hallucinations associated with higher doses of dopamine agonists. The phase 3 data on P2B001 suggest that it can address these challenges.”

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REFERENCES
1. 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 5, 2022. https://www.biospace.com/article/pharma-two-b-announces-positive-topline-results-from-its-pivotal-phase-iii-study-of-p2b001-in-parkinson-s-disease/
2. Onalow WG. Efficacy and safety of P2B001 in the management of early Parkinson’s disease. Results from a phase 3, randomized, double-blind, double-dummy controlled trial. Presented at: AAN Annual Meeting; April 2-7, 2022; Seattle, WA, and virtual. Abstract 011.
3. Pharma Two B Presents Late-Breaker Abstract on Positive Efficacy and Safety Data of P2B001 from Phase 3 Trial at American Academy of Neurology (AAN) Annual Meeting. News release. Pharma Two B. April 5, 2022. Accessed April 5, 2022. https://www.globenewswire.com/news-release/2022/04/05/2416529/0/en/Pharma-Two-B-Presents-Late-Breaker-Abstract-on-Positive-Efficacy-and-Safety-Data-of-P2B001-from-Phase-3-Trial-at-American-Academy-of-Neurology-AAN-Annual-Meeting.html