US and Europe’s Top CF Advocacy Groups Endorse Proteostasis’ Triple-combo Trial Plan

José Lopes, PhD avatar

by José Lopes, PhD |

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Amphotericin for CF

The most influential cystic fibrosis advocacy groups in the United States and Europe have endorsed the idea of a Phase 1 clinical trial to test a triple-combo therapy that Proteostasis Therapeutics has developed, the company announced.

Proteostatis said the endorsements came from the Cystic Fibrosis Foundation’s and European CF Society’s clinical trial arms. The U.S. organization’s trial arm is called the Therapeutics Development Network and the European organization’s the Clinical Trial Network.

The main objectives of the trial are to test the combination’s ability to work in the body, its safety and CF patients’ ability to tolerate it. Researchers will also evaluate its ability to improve patients’ lung function.

Proteostasis developed all three of the combo-therapy components — PTI-428, PTI-801 and PTI-808.

Mutations of the CFTR gene cause cystic fibrosis by generating a faulty version of CFTR protein. The abnormal protein is unable to transport chloride ions across lung cell membranes. This leads to a buildup of mucus in the lungs that disrupts CF patients’ breathing and digestion.

Proteostasis’ triple therapy is designed to improve the body’s ability to transport chloride in the lungs, reducing the thickness of the mucus.

“We are humbled that the two preeminent global CF patient advocacy organizations share our view on the positive potential clinical impact of our CFTR modulators,” Meenu Chhabra, Proteostasis’ president and CEO, said in a press release.

The company expects to begin dosing the trial participants in the first half of 2018 and to have initial results in the second half of the year.

“We believe that PTI-428, PTI-801 and PTI-808 have the potential to be a novel, best-in-class treatment for CF patients,” Chhabra said.

The trial arms of the advocacy organizations study trial proposals to decide whether to endorse the studies. They base their decisions on the scientific merit of the trials, their feasibility, their study design, and whether they support the organizations’ research priorities. The organizations weigh the views of patients and cystic fibrosis experts, including doctors, researchers and trial investigators, before deciding whether to endorse a trial.

Once the Therapeutics Development Network has endorsed a trial, it offers researchers access to a U.S. network of 89 CF centers with trial expertise. It also helps them recruit trial participants.

In Europe, the Clinical Trial Network offers researchers access to 43 CF centers in 15 countries.

The two networks collaborate on trials conducted in both the United States and Europe.

“We are experiencing an exciting time in CF drug development and research, with an unprecedented number of ongoing clinical trials,” said Dr. Patrick A. Flume, the Therapeutics Development Network’s principal investigator. “At the same time, our CF patient population is a valuable and limited resource,” said Flume, who is also director of the Medical University of South Carolina’s Cystic Fibrosis Center.

Both trial networks examined the triple combo’s safety in healthy volunteers who received one dose a day for a week. The participants tolerated the combo well, researchers said.

Laboratory studies have indicated that a combination of PTI-801, PTI-428 and Vertex Pharmaceuticals’ Orkambi (lumacaftor/ivacaftor) is a promising treatment for CF.

Researchers have also been testing some of Proteostasis’ triple-combo components in clinical trials of Orkambi.

A Phase 1 trial (NCT03140527) that has tested PTI-801 and Orkambi support PTI-801 being part of the triple combo, researchers said.

And a Phase 2 trial (NCT02718495) showed that a combination of PTI-428 and Orkambi improved CF patients’ lung function, suggesting PTI-428 was also a good triple-combo candidate.