Proteostasis Therapeutics announced a regulatory update following the completion of a scientific advice meeting with the Medicines and Healthcare Products Regulatory Agency (MHRA), UK, regarding its two pivotal studies, MORE and CHOICES.
Both studies are designed to explore the potential of Proteostasis' proprietary cystic fibrosis transmembrane conductance regulator (CFTR) modulator combinations that include dirocaftor, posenacaftor and nesolicaftor, a CFTR potentiator, corrector and amplifier, respectively. The MHRA's scientific advice outlined a clear path forward toward the initiation and execution of the proposed two-pronged Phase 3 program, including establishment of a common safety database to support the safety profile of the proprietary combination, all toward the goal of supporting a Marketing Authorization Application for dirocaftor, posenacaftor and nesolicaftor. Both trials are expected to begin in 2020 and can run concurrently, building on the safety and efficacy database Proteostasis has established to date in over 300 patients with CF. The Company will continue to seek additional advice from other major regulatory agencies throughout 2020.
"CF is a heterogenous disease whose limited CFTR treatment options leave a significant portion of patients with little or no benefit. This is underscored by what we have demonstrated in our own data, including Phase 2 results comparable to the recently approved CFTR modulator triple combinations, despite a higher disease burden study population, and based on our own market research, where physicians report 1 in 3 patients either discontinuing triple combination treatment for poor tolerability or achieving suboptimal benefit. Our goal is to change this by delivering more choices to patients to better reflect an individualized treatment approach and provide to each patient with CFTR modulators that lead to highest benefit," said Meenu Chhabra, President and Chief Executive Officer of Proteostasis Therapeutics.
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The CHOICES trial (Crossover trial based on Human Organoid Individual response in CF - Efficacy Study) is designed to be the first ever personalized medicine-based study in CF. CHOICES seeks to translate promising responses from an ex vivo organoids study of PTI modulators in rare CF mutations that is part of a pan-European strategic initiative, known as HIT-CF (Human Individualized Therapy of CF), whose goal is to accelerate the development of, and access to, personalized therapies for CF patients. The MORE trial (Modulator Options to RestorE CFTR study) is designed as a global, Phase 3, randomized, placebo-controlled study in CF subjects with the common F508del homozygous mutation, and will seek to confirm the positive efficacy and tolerability results from a recently completed Phase 2 study of the Proteostasis CFTR modulator triple combination.
Nesolicaftor (PTI-428) is an investigational CFTR amplifier in development for the treatment of CF in patients with at least one F508del mutation in the CFTR gene, as part of PTI's proprietary triple combination regimen that includes dirocaftor (PTI-808), a novel potentiator, and posencaftor (PTI-801), a third-generation CFTR corrector. Posencaftor received Fast Track Designation from the U.S. Food and Drug Administration (FDA). In May 2019, nesolicaftor received Orphan Drug Designation (ODD) from the European Commission (EC). In addition to ODD from the EC, nesolicaftor has ODD, Breakthrough Therapy Designation and Fast Track Designation from the FDA.