Combination Extended-Release Pramipexole and Rasagiline Has More Symptomatic Benefit for Parkinson Disease Than Either Agent Alone
In a phase 3 pivotal study (NCT03329508) individuals with Parkinson disease (PD) treated with an extended-release (ER) combination of low dose of pramipexole and rasagiline (P2B001; Pharma 2B, Rehovot, Israel) had symptomatic benefits comparable to pramipexole alone without fewer side effects. Symptoms were measured as change on the Unified Parkinson Disease Rating Scale (UPDRS).
Treatment with combined pramipexole/rasagiline vs pramipexole or rasagiline alone resulted in an adjusted mean change in Total-UPDRS score from baseline of -2.66 points (P=.0018) and -3.30 points (P<.0001), respectively. On the Epworth Sleepiness Scale, combination therapy vs pramipexole alone resulted in an adjusted mean change from baseline of -2.66 points (P<.0001). Fewer treatment-related adverse events were reported with combination therapy vs pramipexole-ER (74.7% vs 86.5%), including memory impairment (0% vs 5.4%), somnolence (14.7% vs 31.1%), and orthostatic hypotension (2.7% vs 12.2%).
These data were presented in the emerging science late-breaking session at the American Academy of Neurology (AAN) Annual Meeting 2022 being held April 2-7 in Seattle, WA and virtually April 24-26.
Dr. Sheila Oren, MD, MBA, chief executive officer of Pharma Two B said, “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.”
Dr. Warren Olanow, professor Emeritus in the Departments of Neurology and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York and chief executive officer of Clintrex Research Corporation said, “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. P2B001 has the potential to become a leading treatment option for patients with Parkinson disease, particularly as first line 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.”
In this study, individuals with early untreated PD (n=544, age 35-80) were randomly assigned to receive treatment with the combined therapy, pramipexole 0.6 mg, rasagiline 0.75 mg, or market-available pramipexole-ER titrated to an effective dose. Pramipexole is a low-dose dopamine agonist, and rasagiline is a low-dose monoamine oxidase-B (MAO-B) inhibitor. Both agents are thought to have efficacy by increasing striatal dopaminergic transmission through potentially synergistic and distinct mechanisms.