Pharma Frontiers: Daily Digest of Global Pharmaceutical News – Aug 30

1.MEK Inhibitor Mirdametinib Granted FDA Priority Review Status

On August 28, SpringWorks Therapeutics announced that the U.S. FDA has accepted their New Drug Application (NDA) for the MEK inhibitor mirdametinib, intended for the treatment of plexiform neurofibromas associated with Neurofibromatosis Type 1 (NF1-PN) in both adult and pediatric patients. The FDA has also granted Priority Review status to the application. The Prescription Drug User Fee Act (PDUFA) target date is set for February 28, 2025. Additionally, the European Medicines Agency (EMA) has completed the validation of the Marketing Authorization Application (MAA) for mirdametinib. According to the press release, mirdametinib has the potential to become the first approved medication for treating adult patients with NF1-PN and is poised to be a "best-in-class" therapy for pediatric patients with NF1-PN. Mirdametinib is an orally bioavailable allosteric small molecule inhibitor targeting MEK1 and MEK2. Both the U.S. FDA and the European Commission have designated mirdametinib as an orphan drug for treating NF1. Furthermore, the FDA has also granted Fast Track designation to this drug for the treatment of NF1-PN in patients aged 2 years and older.

2.Tonghua Golden-Horse Files for Market Approval of New Oral Alzheimer’s Drug

On August 29th, the official CDE website revealed that Tonghua Golden-Horse has filed for market approval for Octahydroaminoacridine succinate, aimed at treating Alzheimer’s disease. Octahydroaminoacridine succinate tablets, developed by Tonghua Golden-Horse, are a small molecule acetylcholinesterase inhibitor that holds completely independent intellectual property rights. The drug simultaneously inhibits both acetylcholinesterase and butyrylcholinesterase, and is primarily used for the treatment of mild to moderate Alzheimer’s disease. In vitro tests have shown that Octahydroaminoacridine succinate’s inhibitory potency on both acetyl and butyryl cholinesterase is several times that of conventional first-line medication, thereby offering better clinical therapeutic effects. Moreover, its clinical efficacy has also been validated through Phase I and Phase II clinical trials. Additionally, Octahydroaminoacridine succinate demonstrates relatively higher safety and security. In September 2023, Tonghua Golden-Horse announced the successful completion of a Phase III study of Octahydroaminoacridine succinate for treating mild to moderate Alzheimer’s disease. The study, which started in January 2017 and completed patient enrollment in August 2021, showed that the tablets significantly improved the cognitive portion of the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) with meaningful clinical implications. In terms of safety, the incidence of adverse events in the Octahydroaminoacridine succinate group was lower than that in the two control groups (placebo and Donepezil hydrochloride). Compared with the placebo group, the results were statistically significant (P<0.001).

3.Neurocrine's Phase II Schizophrenia Drug Study Successful

On August 28th, Neurocrine Biosciences announced that its Phase II study of NBI-1117568 for the treatment of adult schizophrenia achieved positive key data. This was a multicenter, randomized, double-blind, placebo-controlled, multi-arm, dose-finding study (n=210) designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of NBI-1117568 compared to placebo in adult patients initially diagnosed with schizophrenia experiencing acute exacerbation or relapse of symptoms. The primary endpoint of the study was the change in the Positive and Negative Syndrome Scale (PANSS) score from baseline at week 6. The results demonstrated that the study met its primary endpoint. At week 6, the PANSS score in the NBI-1117568 20mg dose group decreased by an average of 18.2 points from baseline, which was clinically meaningful and statistically significant, with a placebo-adjusted decrease of 7.5 points (p=0.011, effect size of 0.61). The study also met other secondary endpoints, including scores on the Clinical Global Impression-Severity (CGI-S), changes in Marder factor scores for positive symptoms, and changes in Marder factor scores for negative symptoms. Additionally, NBI-1117568 demonstrated good safety and tolerability across all doses.

4.UCB's New Drug for Myasthenia Gravis Files for Marketing Authorization in China

On August 28th, the official website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration announced that UCB has applied for market authorization of Zilucoplan injection in China. Zilucoplan is a novel macrocyclic peptide C5 complement inhibitor. It works by inhibiting the activation of the terminal complement pathway and the downstream assembly of the membrane attack complex (MAC), thereby preventing them from disrupting ion channel conduction and neuromuscular signal transmission. In October 2023, the FDA approved the new drug application for zilucoplan (commercial name: Zilbrysq), for the treatment of adult patients with AChR antibody-positive generalized Myasthenia Gravis (gMG). This medication is currently the only once-daily, patient-administered targeted therapy for adult patients with antibody-positive AChR gMG. It reduces the need for frequent hospital visits and enhances patients' independence in managing their medication. Unlike monoclonal antibody C5 inhibitors, Zilucoplan, being a peptide, can be used concomitantly with intravenous immunoglobulin and plasma exchange without the need for supplemental administration.

5.Positive Results from Phase I Study of Krystal Gene Therapy

On August 28, Jeune Aesthetics, a subsidiary of Krystal Biotech, announced positive outcomes from cohorts 3 and 4 in the Phase I PEARL-1 study of the gene therapy KB301, aimed at reversing skin aging. KB301 promotes the production of type III collagen (COL3) by regulating the expression of the type III collagen A1 (COL3A1) gene. The study sought to evaluate KB301's effectiveness in stimulating collagen production to reverse wrinkles, with participants divided into four cohorts. Based on the positive results from cohort 4, Jeune Aesthetics plans to initiate a Phase II study of KB301 targeting dynamic wrinkles on the shoulders. Currently, the FDA has not approved any injectable treatments specifically for cosmetic enhancement of this area.

6.Bayer and NextRNA Reach Nearly $550 Million Collaboration

On August 29th, Bayer and NextRNA Therapeutics announced that they have entered into a collaboration and licensing agreement valued at nearly $550 million. Together, they will develop two potential 'first-in-class' small molecule therapies targeting long non-coding RNAs (lncRNAs), which will enhance Bayer's precision oncology research and development pipeline. Bayer and NextRNA will collaborate on advancing two therapies aimed at tumor indications with significant unmet needs. The first project involves a small molecule therapy targeting lncRNA, currently in the early preclinical development stage. For the second project, NextRNA will continue to investigate lncRNA targets identified by its platform, with Bayer having the option to co-develop one of these targets.

According to the terms of the agreement, NextRNA will receive up to $547 million from the collaboration across the two projects, including upfront payments, near-term milestones, research funding, and other payments related to development and commercial milestones. NextRNA is a biotechnology company focused on developing transformative drugs for lncRNA-driven oncological and neurological diseases. Their approach primarily involves disrupting the interaction between lncRNA and RNA-binding proteins (RBPs) to inhibit the function of disease-related lncRNAs. NextRNA's proprietary platform combines its computational engine, NextMap, with extensive expertise in lncRNA biology, along with diverse biochemical, biophysical, and chemical functionalities.

7.Pfizer and Flagship Expand Collaboration

On August 29th, Pioneering announced a further acceleration in its strategic collaboration with Pfizer. Quotient Therapeutics, a company established by Flagship, is set to work with Pfizer on two research projects. The partners will analyze somatic mutations occurring in patient tissues to guide the discovery and development of potentially transformative therapies for cardiovascular and kidney diseases. Pioneering Medicines, a drug discovery and development division under Flagship, is leading the strategic collaboration with Pfizer. This includes propelling the exploration process and swiftly identifying potential drug development projects based on Flagship's diverse biological platforms and models. The agreement with Quotient marks the latest initiative following Flagship's announcement of a strategic partnership with Pfizer in July 2023.

Quotient Therapeutics specializes in systemic research into the genetic variations and evolution of trillions of cells within the human body. The company's technology platform performs high-precision and high-resolution genetic sequencing on tissues obtained from patient lesions, revealing the relationships between somatic genetic mutations and diseases. This drives the discovery of transformative drugs aimed at curing, preventing, or reversing diseases. Quotient was founded by Flagship Pioneering in 2022 and is supported by experts in the field of somatic genetics.

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