Pharma Two B Announces Positive Topline Results from its Pivotal Phase III Study of P2B001 in Early Parkinson's Disease

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REHOVOT, Israel, Dec. 15, 2021 /PRNewswire/ -- Pharma Two B Ltd., a privately held company developing innovative therapeutics based on reformulation and combinations of previously approved drugs for neurological indications, today announced that its Phase III double-blind, active-controlled study of P2B001 in early Parkinson's disease (PD) successfully met its primary and key secondary endpoints.

P2B001 is a novel fixed-dose combination of extended release (ER) formulations of pramipexole (0.6mg) and rasagiline (0.75mg), with both components at lower doses than their respective marketed products.  In the Phase III study, P2B001 was superior to each of its individual components as measured by the change from baseline to week 12 in total Unified Parkinson's Disease Rating Scale (UPDRS Part II and III; primary endpoint). P2B001 was superior to the pramipexole component by 2.66 points (p=0.0018) and superior to the rasagiline component by 3.30 points (p=0.0001).

In addition, P2B001 demonstrated comparable efficacy to a marketed pramipexole ER (titrated to an optimal dose for each individual patient; 1.5-4.5 mg) with significantly less daytime sleepiness (somnolence), by a reduction of 2.66 points (p<0.0001) as measured by Epworth Sleepiness Scale (ESS; key secondary endpoint). P2B001 fixed dose and the marketed titrated pramipexole ER showed similar changes in total UPDRS scores after 12 weeks (-7.98 points and -8.35 points, respectively).

"We are thrilled with the positive outcome of this rigorous Phase III 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," said Dr. Sheila Oren, M.D., M.B.A., Chief Executive Officer of Pharma Two B. "The data from this Phase III 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".

Jeffrey Berkowitz, Chairman of the Board of Pharma Two B commented: "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.  Importantly, these robust results are consistent with our prior pivotal double-blind placebo-controlled Phase IIb study of P2B001 in PD, which successfully met all primary and secondary endpoints¹. Based on the Phase IIb data and the Phase III topline results, we are preparing the regulatory submission for P2B001 and plan to submit a New Drug Application to the FDA in 2022."

Topline Results

P2B001 Met Primary Endpoint
- The adjusted mean change from baseline to week 12 in Total-UPDRS score was -2.66 points for P2B001 versus pramipexole 0.6 mg (p=0.0018) and -3.30 points for P2B001 versus rasagiline 0.75 mg (p=0.0001)

P2B001 Met Key Secondary Endpoint
- The adjusted mean change from baseline to week 12 in ESS score for P2B001 versus the marketed pramipexole ER was -2.66 points (p<0.0001)

Calibration of P2B001 and Pramipexole ER
- The adjusted mean change in total UPDRS score from baseline to week 12 for P2B001 (-7.98 points) and the marketed pramipexole ER (-8.35 points) are comparable

P2B001 Showed a Favorable Side Effect Profile 
- P2B001 was generally well tolerated, with more than 98% of treatment-emergent adverse events (TEAEs) being mild or moderate in severity.  Early treatment termination rates were similar across treatment groups (between 7.1% - 9.1%).

Treatment-emergent adverse events (TEAE) reported in >5% of participants in any arm

Dr. Warren Olanow, Professor Emeritus of Neurology and Neuroscience at the Icahn School of Medicine at Mount Sinai in New York, commented, "The initiation of treatment of patients with Parkinson's disease represents an area of unmet need due to the side effects associated with current treatments. Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages.  The results demonstrated both superior efficacy to components and a more favorable safety profile than treatment with standard doses of pramipexole.  If approved, P2B001 would enable patients to be treated with an effective dose of a dopamine agonist, yet with less adverse events often seen with this class of drugs, including daytime sleepiness, orthostatic hypotension, and hallucinations.  These issues can often negatively affect patients' activities of daily living. P2B001 has the additional advantage of once-a-day administration without the need for titration."

Dr. Robert A. Hauser, M.D., M.B.A, Professor of Neurology and Director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida, commented, "The prevalence of Parkinson's disease increases with age, and it is the fastest growing neurological disorder across the globe.  With increased life expectancy and longer disease duration, patients will often require dopaminergic replacement therapies for many years.   P2B001 has the potential to offer a solution that is easy to use, provides good symptomatic control and a favorable safety profile, and may reduce or delay levodopa-associated motor complications.  If approved, this product will be an important new option when considering a long-term care plan for people with early-stage Parkinson's disease." 

Phase 3 Study Design
The study was a 12-week, multinational, randomized, double-blind, double-dummy, active-controlled, parallel group study designed to determine the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in people with early Parkinson's disease.  It was conducted at 70 centers in the US, Europe, and Canada.  A total of 544 participants were randomized to one of four treatment arms: P2B001, a once daily ER combination product (comprised of pramipexole 0.6 mg and rasagiline 0.75 mg); pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; and the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5 to 4.5 mg). The primary endpoint was the change in total Unified Parkinson's Disease Rating Scale (UPDRS, defined as the sum of parts II and III) for P2B001 as compared to each of its individual components over 12 weeks.  Secondary endpoints included a comparison of P2B001 with the calibration arm (currently marketed pramipexole ER) with regard to changes in the Epworth Sleepiness Scale (ESS) score, as well as comparison of P2B001 to its individual components in the motor (Part III) and activities of daily living (Part II) components of the UPDRS score, PDQ-39 ADL subscore, and PDQ-39 total score.  For more information, refer to ClinicalTrials.gov Identifier: NCT03329508.

About Pharma Two B
Pharma Two B is a clinical-stage pharmaceutical company that is developing differentiated and value-added products, based on reformulation and combinations of previously approved orally-administered drugs for neurological indications. The company aims to improve efficacy, safety and delivery profiles and address unmet medical needs while minimizing timelines to FDA approval via the 505(b)(2) pathway. The company's lead product P2B001 is being investigated as a treatment for early-stage Parkinson's disease. Pharma Two B is led by a highly experienced team, supported by prominent scientific and clinical key opinion leaders, and backed by a dedicated group of investors.  For more information, please visit: www.pharma2b.com.

Forward Looking Statements
Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as" "will," "expect," "could," "if," "expected"," "anticipate"," look forward", "believe" "potential," "propose" and "continue" or negative variants of such terms. These and similar forward-looking statements discuss the company's future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially.

Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results.

Reference:
¹ Olanow, CW et al., A Randomized Trial of a Low-Dose Rasagiline and Pramipexole Combination (P2B001) in Early Parkinson's Disease. Mov Disord. 2017;32(5):783-789. doi: 10.1002/mds.26941.

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SOURCE Pharma Two B Ltd.