pramipexole/rasagiline (P2B001) / Pharma Two B, Myung In Pharm, Zhejiang Jingxin Pharma - LARVOL DELTA

Pharma Two B Announces Poster Presentation on P2B001 at the Annual Meeting of the Parkinson’s Disease Study Group (GlobeNewswire) - "Pharma Two B...today announced a poster presentation of integrated safety and efficacy data on P2B001 from its Phase 2b and Phase 3 studies in early-stage Parkinson’s disease (PD) patients...The poster summarizes an integrated modified-ITT analysis of Unified Parkinson’s Disease Rating Scale (UPDRS) results in 196 early-stage PD patients, as follows: i) P2B001 had significantly greater effect on the UPDRS Part II (Activities of Daily Living, or ADL), Part III (Motor), and Total (Parts II and III) scores versus placebo. ii) P2B001 had comparable efficacy to individually titrated PramiER. iii) P2B001 had significantly less worsening in daytime-sleepiness compared to those treated with PramiER. iv) P2B001 was well-tolerated with an adverse event profile that included fewer sleep-related and dopaminergic adverse events than titrated doses of PramiER."

P2b data • P3 data • CNS Disorders • Parkinson's Disease

Pharma Two B Announces Plans to Go Public via Merger with Hepion Pharmaceuticals, Inc. and Concurrent $11.5 Million Private Placement (Hepion Pharma Press Release) - "Hepion Pharmaceuticals, Inc...today announced it has entered into a definitive merger agreement (the 'Merger Agreement') with Pharma Two B Ltd...'We are excited about Pharma Two B’s next growth phase, moving P2B001 towards an NDA submission targeted for the first half of 2026 and making this potential treatment available to patients,'...Hepion has also announced a private placement of $2.9 million non-convertible senior notes to qualified institutional investors...In support of the Merger, Pharma Two B has entered into a securities purchase agreement for an $11.5 million private placement of ordinary shares (or pre-funded warrants in lieu thereof) and accompanying Series A warrants and Series B warrants with a syndicate of new and existing institutional life science investors."

FDA filing • Financing • M&A • CNS Disorders • Parkinson's Disease

Emerging Novel Therapies in Development for PD (NeurologyLive) - "Kremens gave thoughts on the use of several investigational continuous agents, including IPX203, risvodetinib, and P2B001."

Video

Safety and Tolerability of P2B001 in Patients with Early Parkinson's Disease: Analysis of an Integrated Phase 2 and 3 Safety Database (AAN 2024) - P2b, P3 | "Objective:Evaluate and characterize the safety and tolerability profile of P2B001.Background:P2B001 is a once-daily, no titration, combination of low-dose, extended-release (ER) formulations of pramipexole and rasagiline (0.6/0.75mg), under investigation for patients with early Parkinson's disease (PD). P2B001 may offer patients with early PD a convenient, first-line, once-daily treatment with a favorable safety and tolerability profile compared to commercially available PramiER. P2B001-related AEs were mainly mild-moderate; no ICD-related concerns were observed."

Clinical • P2 data • CNS Disorders • Fatigue • Insomnia • Movement Disorders • Parkinson's Disease • Sleep Disorder

Pharma Two B Announces Publication of Positive Phase 3 Study Results of P2B001, an Investigational Treatment for Early Parkinson’s Disease, in Movement Disorders (GlobeNewswire) - P3 | N=544 | NCT03329508 | Sponsor: Pharma Two B Ltd. | "Pharma Two B...today announced that data from a Phase 3 study evaluating P2B001...were published in Movement Disorders....The change from baseline in total UPDRS (primary endpoint) showed that P2B001 was significantly superior to each of its individual components demonstrating that each contributed to the P2B001 benefit. Least squares mean (LSM) (standard error) treatment difference between P2B001 and pramipexole ER (PPX-ER 0.6 mg) was –2.66 ± 0.85 points (p = 0.0018), and between P2B001 and rasagiline ER (RAS-ER 0.75 mg) was –3.30 + 0.85 points (p = 0.0001). The change from baseline to week 12 in total UPDRS score between P2B001 and PramiER (individually titrated to optimal dose; mean, 3.2 mg/day) was not significantly different (–8.35 ± 0.86 vs. 7.98 ± 0.60; p = 0.7197)."

P3 data • CNS Disorders • Parkinson's Disease

Pharma Two B to Present Additional Phase 3 Positive Results of P2B001, a once-daily, fixed-dose combination of low-dose pramipexole and low-dose rasagiline, at 2023 International Congress of Parkinson’s Disease and Movement Disorders (GlobeNewswire) - P3 | N=544 | NCT03329508 | Sponsor: Pharma Two B Ltd. | "Pharma Two B...today announced that sub-group analysis results from the Phase 3 pivotal clinical trial evaluating P2B001 are being presented at the 2023 The International Parkinson and Movement Disorder Society® annual meeting, August 27-31, in Copenhagen, Denmark. The data are being presented as a poster presentation on Monday, August 28....The efficacy and safety profile of P2B001 was not significantly different in younger versus older patients (66 years), nor when patients were analyzed by baseline severity (≤29 vs >29 Total-Unified Parkinson’s Disease Rating Scale (UPDRS) score). Across all subgroups, P2B001 provided numerically greater symptomatic benefit versus its components, as assessed by Total-UPDRS, and statistically significant greater benefit in Activities of Daily Living (UPDRS Part II) versus components."

P3 data • CNS Disorders • Parkinson's Disease

Pharma Two B to Present Additional Positive Results from P2B001 Phase 3 Trial at 2023 American Academy of Neurology Annual Meeting (GlobeNewswire) - P3 | N=544 | NCT03329508 | Sponsor: Pharma Two B Ltd. | "Pharma Two B...today announced that additional results from the Phase 3 pivotal clinical trial evaluating P2B001, will be presented at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27 in Boston, MA....Results highlighted in abstract 2396 show that patients treated with P2B001 developed significantly less new-onset EDS, often a limiting factor for traditional dosing of DAs. Data analysis showed the rate of new-onset EDS was significantly lower in patients treated with P2B001 (8.5%) as compared to commercial Prami-ER (35.7%; adjusted odds ratio 0.17 (95% CI: 0.08-0.36; P<0.0001)."

P3 data • CNS Disorders • Parkinson's Disease

Pharma Two B to Present Additional Positive Results from P2B001 Phase 3 Trial at 2023 American Academy of Neurology Annual Meeting (GlobeNewswire) - P2/3 | N=149 | NCT01968460 | Sponsor: Pharma Two B Ltd. | "The results presented in abstract 3733 demonstrate comparable changes from baseline to week 12 with P2B001 and commercial Prami-ER in total UPDRS scores (-7.98 ±0.6 vs -8.35 ±0.86, p=0.7197) and non-inferiority (post-hoc) of P2B001 was confirmed (margin of 3 points, p=0.0052). Similarly, no significant differences between P2B001 and Prami-ER were seen in total UPDRS responders (≥4-point improvement), UPDRS Part II (activities of daily living/ADL) and UPDRS Part III (motor) scores."

P2/3 data • CNS Disorders • Parkinson's Disease

P2B001 (low dose combination of extended-release pramipexole and rasagiline) versus titrated extended-release pramipexole in the management of early Parkinson’s disease: Exploratory findings from a randomized, controlled trial (AAN 2023) - "Rates of somnolence (14.7% versus 31.1%) and orthostatic hypotension (2.7% versus 12.2%) were also lower with P2B001 compared with Prami-ER. Conclusions These data indicate that P2B001 offers a once daily treatment option (without the need for titration) for patients with early PD with comparable efficacy to marketed Prami-ER but with reduced sleep-related and dopaminergic side effects."

Clinical • CNS Disorders • Hypotension • Movement Disorders • Parkinson's Disease

P2B001 significantly reduced risk of daytime sleepiness: results from a randomized controlled phase 3 trial with active pramipexole arm in early Parkinson’s disease (PD) (AAN 2023) - "Design/Methods Untreated patients (time from diagnosis<3 years) were randomized (2:2:2:1) to 12-weeks double-blind treatment with P2B001, pramipexole-ER-0.6mg (PPX), rasagiline-ER-0.75mg (RAS), or marketed ER-PPX (6-week titration). Conclusions EDS is a limiting factor for traditional dosing of DAs. With similar efficacy to ER-PPX monotherapy, patients treated with P2B001 developed significantly less new-onset EDS and fewer sleepiness-related TEAEs."

Clinical • P3 data • CNS Disorders • Excessive Daytime Sleepiness • Movement Disorders • Parkinson's Disease • Sleep Disorder

A Phase 3 Study With P2B001 in Subjects With Early Parkinson's (clinicaltrials.gov) - P3 | N=544 | Completed | Sponsor: Pharma Two B Ltd. | Unknown status ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Pharma Two B Presents Positive Efficacy and Safety Data of P2B001 from Phase 3 Trial at the MDS International Congress of Parkinson's Disease and Movement Disorders (GlobeNewswire) - "Pharma Two B Ltd. today announced that positive efficacy and safety data from its recently completed randomized, controlled Phase 3 trial of investigational P2B001 in the management of early PD will be presented at the MDS International Congress of Parkinson's Disease and Movement Disorders® Sept. 15-18 in Madrid. The data will be presented in various formats, including a guided poster tour, an e-poster and video on the MDS Congress virtual platform, and publication in the Movement Disorders journal supplement."

P3 data • CNS Disorders • Parkinson's Disease

Novel Combo Drug Shows Promise as First-Line Parkinson's Treatment (Medscape) - "Commenting on the study for Medscape Medical News, Alfonso Fasano...agreed that better therapeutic options are needed for Parkinson's....'Conducting large clinical trials like this one is expensive, and I wonder about the cost of the drug when approved,' Fasano noted. 'Do we really need to invest in combination pills containing two already well-known compounds?'"

Media quote

Pharma Two B Presents Late-Breaker Abstract on Positive Efficacy and Safety Data of P2B001 from Phase 3 Trial at American Academy of Neurology (AAN) Annual Meeting (GlobeNewswire) - "Pharma Two B Ltd...announced that the efficacy and safety data from its recently completed Phase 3, randomized controlled trial of P2B001 in the management of early Parkinson’s disease is being presented today, April 5th, as an oral presentation in the Emerging Science late-breaking session at the American Academy of Neurology (AAN) annual meeting in Seattle."

Late-breaking abstract • P3 data • CNS Disorders • Parkinson's Disease

P2B001 (Extended Release Pramipexole and Rasagiline): A New Treatment Option in Development for Parkinson's Disease. (PubMed, Adv Ther) - "In this drug evaluation, we review the preclinical and current clinical data for P2B001 and its components. The P2B001 combination has the potential to provide greater efficacy than either pramipexole or rasagiline alone and a better tolerability profile compared to higher dosage dopamine agonist monotherapy, while maintaining the advantage of lower motor complication risk than levodopa."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Pharma Two B KOL Webinar (Businesswire) - "Pharma Two B Ltd...today announced that it will host a key opinion leader (KOL) event to discuss the positive results from the pivotal Phase III Study of P2B001 in early Parkinson’s Disease (PD)..."

Live event

Pharma Two B to Host a Virtual KOL Event on Successful Phase III Study Results of P2B001 in Parkinson’s Disease (PD) (GlobeNewswire) - "Pharma Two B Ltd...today announced that it will host a key opinion leader (KOL) event to discuss the positive results from the pivotal Phase III Study of P2B001 in early Parkinson’s Disease (PD) on Thursday, January 27, 2022 from 11am – 12pm Eastern Time....The Company is planning to file an NDA for P2B001 in H2 2022."

NDA • P3 data • CNS Disorders • Parkinson's Disease

Jingxin Pharmaceutical: Two new drugs in the field of neuropsychiatric and cardiovascular and cerebrovascular fields reached phase III clinical endpoints [Google translation] (Eastmoney.com) - "At present, Jingxin Pharmaceutical has completed the IND application of the P2B001 project in the China Food and Drug Administration, and signed a cooperation agreement with the company, and has the exclusive development and commercialization authorization of the project in China."

Licensing / partnership • New trial • CNS Disorders • Parkinson's Disease

Pharma Two B Announces Positive Topline Results from its Pivotal Phase III Study of P2B001 in Early Parkinson’s Disease (GlobeNewswire) - P3, N=525; NCT03329508; Sponsor: Pharma Two B Ltd.; "Pharma Two B...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 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)....'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.'...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)."

NDA • P3 data: top line • CNS Disorders • Parkinson's Disease

Pharma Two B Announces Licensing and Investment Agreement with Myung In Pharm (MIP) for P2B001 in South Korea (GlobeNewswire) - "Pharma Two B Ltd...today announced that it has entered into an exclusive licensing agreement with Myung In Pharm Co. Ltd...to commercialize P2B001 for Parkinson’s disease (PD) in South Korea. In addition, Myung In Pharm invested $5 million of equity in Pharma Two B....Under the terms of the agreement, Myung In Pharm will seek regulatory approval for P2B001 in South Korea and will manufacture, commercialize and distribute P2B001 in the region. Myung In Pharm will be responsible for all expenses related to the registration, sales, marketing and distribution of P2B001 in South Korea. In addition to the $5 million equity investment by Myung In Pharm, Pharma Two B is entitled to royalties on sales of P2B001 in the region."

Licensing / partnership • CNS Disorders • Parkinson's Disease

Pharma Two B Announces Last Patient Out in Phase III Study of P2B001 in Early Parkinson’s Disease (GlobeNewswire) - "Pharma Two B Ltd...announced that the last patient in its multinational Phase III study of P2B001 in early PD has now completed the study. Top line results from the study are expected in the fourth quarter of 2021."

P3 data: top line • Trial completion • CNS Disorders • Parkinson's Disease

A Phase 3 Study With P2B001 in Subjects With Early Parkinson's (clinicaltrials.gov) - P3; N=525; Active, not recruiting; Sponsor: Pharma Two B Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

Effect of continuous and multi-phasic current profiles on the iontophoretic transport of pramipexole, rasagiline and huperzine A: Depicting temporal variation and biodistribution in the skin. (PubMed, Int J Pharm) - "Current density and duration of current application were also shown to have a significant impact on the skin biodistribution of PRA. These results also provide insight into the rate of formation of iontophoretic drug reservoirs in the skin."

Journal • CNS Disorders • Immunology

Comparison chart: Drugs for Parkinson's disease. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

A Phase 3 Study With P2B001 in Subjects With Early Parkinson's (clinicaltrials.gov) - P3; N=525; Recruiting; Sponsor: Pharma Two B Ltd.; Trial completion date: Feb 2021 ➔ Oct 2021; Trial primary completion date: Dec 2020 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease