Proteostasis Therapeutics announced plans to open two Phase 3 clinical trials of its triple combination therapy candidate for cystic fibrosis this year, after a meeting with the chief healthcare regulatory office for the U.K.
One of these pivotal trials will be investigating the possibility of organoids being used for personalized medicine in CF.
At the meeting, officials with the Medicines and Healthcare Products Regulatory Agency (MHRA) — the U.K.’s equivalent of the U.S. Food and Drug Administration — outlined safety and other steps necessary to conducting these pivotal trials in ways that would support future regulatory approval, Proteostasis said in a press release.
MORE and CHOICES, as the Phase 3 studies will be known, intend to explore combinations of the company’s cystic fibrosis transmembrane conductance regulator (CFTR) modulators. These modulators are compounds that act directly on the faulty proteins that cause CF.
The combinations to be tested in these trials include a CFTR potentiator called dirocaftor (previously known as PTI-808), the CFTR corrector posenacaftor (PTI-801), and the CFTR amplifier nesolicaftor (PTI-428).
The CHOICES trial (Crossover trial based on Human Organoid Individual response in CF – Efficacy Study) aims to build on the positive results from an EU initiative called HIT-CF (Human Individualized Therapy of CF), where the company’s CFTR modulators were tested on organoids (three-dimensional organ models created from stem cells). Cells for these organoids came from patients with rare CF mutations.
Researchers in the CHOICES trial will be testing the potential triple combo treatment on patients whose organoids responded favorably to the agents, a first step in establishing if organoids can be used to personalize treatment for people with CF.
The MORE trial (Modulator Options to RestorE CFTR study) is a worldwide, randomized and placebo-controlled study in CF patients with two copies of the F508del mutation in the CFTR gene (the most common CF mutation).
MORE will attempt to confirm a Phase 2 study’s results showing lung function benefits in patients given this triple combination, as well as safety and efficacy. The greatest benefits, both in lung health and sweat chloride levels, were seen in those with two copies of the F508del mutation.
“CF is a heterogenous disease whose limited CFTR treatment options leave a significant portion of patients with little or no benefit,” Meenu Chhabra, president and CEO of Proteostasis, said in the release.
“[B]ased on our own market research … physicians report 1 in 3 patients either discontinuing triple combination treatment for poor tolerability or achieving suboptimal benefit,” Chhabra added. “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.”
Proteostasis will continue to work with MHRA and other regulatory agencies, including the European Medicines Agency and the FDA, as it continues to advance dirocaftor, posenacaftor and nesolicaftor in development, Chhabra said.
“We value the opportunity to engage with regulators who recognize this challenge, and we are pleased that the Company’s preclinical and clinical programs were in line with MHRA expectations for the conduct of our pivotal program,” she said.
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