At the American Academy of Neurology (AAN) 2024 Annual Meeting, Pharma Two B presented new safety and tolerability data for P2B001 (pramipexole ER and rasagiline ER 0.6mg/0.75mg) from its Phase II and Phase III clinical trials in Parkinson’s disease (PD) patients.
The presentation demonstrated the safety profile of P2B001 and its potential to offer an additional treatment for patients with early-stage PD.
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Levodopa has been the standard of care (SOC) for the symptomatic treatment of PD for the past five decades.
However, most patients on levodopa for an average of five years may experience motor complications such as levodopa-induced dyskinesia, which is an involuntary, erratic, writhing movement of the arm, leg, face, or the entire body, a consequence of long-term levodopa treatment.
Key opinion leaders (KOLs) previously interviewed by leading data and analytics company GlobalData reported that early-stage PD patients between 40-60 years of age would be prescribed monoamine oxidase B (MAO-B) inhibitors or dopamine agonists, as there may be fewer levodopa-related motor complications as the disease progresses, and the patients are more likely to tolerate the treatment-emergent adverse events (TEAEs) than patients over 70 years.
As such, levodopa therapy is a first-line treatment for early-stage PD patients over 70 years.
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By GlobalDataP2B001 is a fixed combination of extended-release (ER) formulations of pramipexole and rasagiline in a single pill with once-daily dosing.
Although the use of pramipexole and rasagiline is well-established as monotherapies or adjunctive therapies for the treatment of PD, P2B001 is set to be the first oral pill combining a dopamine agonist and MAO-B inhibitor in a single pill for the treatment of PD.
P2B001 contains 0.6mg of pramipexole ER, which is much lower than the typical dosage of marketed pramipexole at 1.5-4.5mg per day.
In addition, the ER formulation of rasagiline is not commercially available.
KOLs previously interviewed by GlobalData stated that as P2B001 combines two low-concentration drugs in a single pill, it will slightly lessen the pill burden for PD patients.
In the Phase III study, P2B001 was compared against its individual components of low-dose pramipexole and low-dose rasagiline, and an optimised dose of the commercially available pramipexole ER (individually titrated to a dose based on the clinical staff’s assessment of subject’s satisfaction and tolerability; the mean dose of pramipexole ER was 3.2mg).
The study found that P2B001 was more efficacious than its individual components and had a comparable efficacy to 3.2mg pramipexole ER, as assessed by Change in Total Unified Parkinson’s Disease Rating Scale (UPDRS) total score of parts II and III.
At the AAN 2024 ‘Movement Disorders: Clinical Trials in Movement Disorders’ presentation, Pharma Two B’s presentation reported on the safety and tolerability profile of P2B001.
The study evaluated a total of 323 early-stage PD patients who were enrolled in the Phase II and Phase III trials.
The average age of participants was 64 years old and the average time since diagnosis was six months.
In addition, baseline characteristics included an average UPDRS score of 28-29 and a Hoehn and Yahr stage of less than 3.
In the study, they found that the TEAEs associated with P2B001 were mild to moderate, and the number of TEAEs was consistently less than those observed with 3.2mg of pramipexole ER.
Furthermore, there was a lower frequency of dopaminergic TEAE with P2B001 compared with pramipexole ER, including incidences of orthostatic hypertension, gastrointestinal side effects, and neuropsychiatric complications such as hallucinations and memory impairment.
While the dopaminergic TEAEs emerged in the first four weeks of P2B001 treatment, the increased frequency persisted with pramipexole ER across the dosing period.
In addition, the rate of somnolence for pramipexole ER was almost double that of patients treated with P2B001.
As such, P2B001 demonstrated a favourable safety and tolerability profile compared to the commercially available pramipexole ER.
However, KOLs previously interviewed by GlobalData noted that they often do not prefer combinations of two different molecules with distinct mechanisms of action as it makes it difficult to understand whether the patient has a reaction to one portion of the combinational pill and not the other.
Moreover, prescribers are unable to titrate each drug accordingly.
In addition, P2B001 is anticipated to have premium pricing and would face significant competition from cheap generic dopamine agonists and MAO-B inhibitors.
Should P2B001 receive regulatory approval, the lack of flexibility in adjusting the dose for each of the combined drugs and the wide availability of generic MAO-B inhibitors and dopamine agonists is expected to cause a slow initial uptake of P2B001.
However, P2B001 would offer an alternative treatment for early-stage PD patients, particularly those who have not had a good experience with pramipexole ER.
