Novel polypill a potential first-line therapy for Parkinson’s disease

Taking P2B001, a novel polypill comprising fixed-dose combination of 0.6 mg pramipexole (PPX) and 0.75 mg of rasagiline (RAS), was better than taking either drug component alone for symptomatic control of Parkinson’s disease, according to results of a late-breaking phase III study presented at AAN 2022.

At 12 weeks, patients treated with P2B001 had significantly better performance on a battery of standard tests for parkinsonian symptoms, as indicated by improvements in the UPDRS*-Total score from baseline, compared with those who took individual components of the drug (mean change, -7.98 vs -5.32 and 4.69 for P2B001 vs PPX 0.6 mg [p=0.0018] and RAS 0.75 mg [p=0.0001], respectively). [AAN 2022, abstract 011]

In the phase III, double-blind, double-dummy study, 544 patients (aged 35–80 years) with early Parkinson's disease who were previously untreated were randomized in a 2:2:2:1 ratio to receive P2B001, PPX 0.6 mg, extended-released (ER) RAS at fixed-dose of 0.75 mg, or marketed version of ER-PPX requiring titration for 12 weeks.

PPX is a dopamine agonist, whereas RAS is a monoamine oxidase inhibitor, which is currently available on the market in a format requiring titration. The P2B001 polypill therefore provides a convenient fixed-dose administration without the need to titrate.

While showing good efficacy, PPX and RAS were placed as second- and third-line therapy, respectively, after levodopa in current treatment guidelines due to their greater rates of side effects. In addition to sleepiness — which is common with dopaminergic interference, other potential dopaminergic side effects include orthostatic hypotension, gastrointestinal problems, and psychobehavioral symptoms.

Compared with the titrated ER-PPX, P2B001 was similar in efficacy (treatment difference, 0.37; p=0.71) but came with the benefit of fewer side effects. The P2B001 group experienced significantly less daytime sleepiness than those on titrated ER-PPX (mean changes in ESS**-Total scores from baseline, -0.33 vs 2.33; p<0.0001).

Other dopaminergic adverse events (AEs) also occurred in fewer patients in the P2B001 than the titrated ER-PPX groups (44.7 percent vs 66.2 percent), including somnolence (14.7 percent vs 31.1 percent) and orthostatic hypotension (2.7 percent vs 12.2 percent).

“The study met its primary and secondary endpoint and treatment was well-tolerated with fewer dopaminergic AEs than [titrated] ER-PPX,” said the researchers.  

“These findings support the potential of P2B001 as a first-line, once-daily treatment for people with early Parkinson’s disease that offers effective symptomatic control with a favourable safety profile and no need for titration,” they added.

*UPDRS: Unified Parkinson's Disease Rating Scale

**ESS: Epworth Sleepiness Scale