P2B001 Meets Phase 3 Primary, Secondary End Points in Early Parkinson Disease
Pharma Two B anticipates filing a new drug application to the FDA for the investigational treatment in 2022.
Sheila Oren, MD
The phase 3 trial of P2B001 (NCT03329508) met its primary and key secondary end points in early Parkinson disease (PD), Pharma Two B recently announced. Following data from the phase 2b trial (NCT01968460) and positive topline results from the phase 3 study, regulatory submission for P2B001 is in development, and Pharma Two B plans to submit a new drug application to the FDA in 2022.1
P2B001 is a novel, fixed-dose combination of extended-release (ER) formulation of pramipexol (Mirapex; Pharmacia & Upjohn) and rasagiline (Azilect; Teva Pharmaceuticals), 2 treatments previously approved for PD. Their doses in P2B001—0.6 mg of pramipexole and 0.75 mg of rasagiline—are lower than in respective marketed products.
In the phase 3 trial of P2B001, the treatment combination demonstrated superior efficacy when compared to the individual components, measured by change in Unified Parkinson’s Disease Rating Scale (UPDRS Part II and III) scores from baseline to week 12. Compared with the pramipexole component, P2B001 was superior by 2.66 points (P = .0018), and compared with the rasagiline component, P2B001 was superior by 3.30 points (P = .0001).
P2B001 also met its key secondary end point in demonstrating comparable efficacy to a marketed pramipexole ER, which was titrated for each patient, ranging between 1.5-4.5 mg. Patients treated with P2B001 had significantly less daytime sleepiness, measured by the Epworth Sleepiness Scale (ESS), reducing somnolence by 2.66 (P <.001). Similar changes were observed in UPDRS scores after 12 weeks for both P2B001 fixed-dose and the marketed titrated pramipexole ER, with a decrease in 7.98 points and 8.35 points, respectively.
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“We are thrilled with the positive outcome of this rigorous phase 3 study. There is a clear unmet medical need for an early PD treatment that can significantly improve motor symptoms and daily function, while avoiding side effects," Sheila Oren, MD, CEO, Pharma Two B, said in a statement.1 "The data from this phase 3 study support our view that P2B001 can provide clinical benefits comparable to higher doses of commercially available dopamine agonists, while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension and hallucinations. This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists. We would like to thank all of the study participants and investigational sites that took part in this important study.”
Investigators also observed a favorable adverse effect profile for P2B001, and the treatment was generally well-tolerated. Of the treatment-emergent adverse events (TEAEs) reported, more than 98% were mild to moderate in severity rate. The most common TEAEs were somnolence, nausea, fatigue, and orthostatic hypotension. Early treatment termination rates were similar across treatment groups, ranging between 7.1%-9.1%.
"We believe these results are transformative for Pharma Two B and we are excited to complete the regulatory submissions and prepare for a commercial launch,” Jeffrey Berkowitz, chairman of the board, Pharma Two B, said in a statement.1 “Importantly, these robust results are consistent with our prior pivotal double-blind placebo-controlled phase 2b study of P2B001 in PD, which successfully met all primary and secondary end points.”
The phase 3 trial was a 12-week randomized, double-blind parallel group study conducted in 70 centers in the US, Europe, and Canada. A total of 544 participants were enrolled, randomized to 1 of 4 treatment arms, P2B001 (combination of pramipexole 0.6 mg/rasagiline 0.75 mg once daily), pramipexole ER capsule (0.6 mg once daily), rasagiline ER capsule (0.75 mg once daily), or the currently marketed produced pramipexole ER capsules (titrated to an optimal dose for each patient, between 1.5-4.5 mg).
In 2015, Pharma Two B reported topline results from the phase 2b study, which included 149 patients with early-stage PD randomized in a similar fashion. At the end of the 12-week trial period, investigators concluded that the investigational therapy met primary and secondary end points for both dose combinations.2
