Phase 1 Trial of CF ‘Corrector’ May Be First Step Toward Triple Combination Therapy

Joana Fernandes, PhD avatar

by Joana Fernandes, PhD |

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Digestion therapy trial design

A Phase 1 clinical trial will evaluate the safety and tolerability of GLPG2737 as a possible treatment for cystic fibrosis (CF), Galapagos NV announced.

CF is caused by mutations in the CFTR gene, which encodes a protein channel with the same name. When mutated, this protein can no longer transport chloride ions across cell membranes, leading to the accumulation of mucus in several organs, which can result in bacterial growth and infection.

Galapagos and AbbVie  are collaborating to design CF therapies, aiming for a triple combination therapy that corrects and restores CFTR channel activity (corrector drugs), which is deficient in CF patients, and allows for the channel’s proper opening (potentiator drugs). GLPG2737 is the first next-generation (C2) corrector molecule being developed, and the final component needed to complete a first triple combination therapy.

The randomized, placebo-controlled study will be carried out in the Netherlands, enrolling at least 64 healthy participants. GLPG2737 will be administered as a single, oral treatment. The first part of the study will test a range of single ascending doses in the volunteers, and the second part will evaluate the effect of multiple ascending doses of GLPG2737 given daily for 14 days.

“We are pleased to initiate a Phase 1 study with the first of our C2 correctors for cystic fibrosis,” said Piet Wigerinck, CSO of Galapagos, in a news release. “This step brings us closer to our goal of initiating a patient evaluation of a triple combination therapy by mid-2017.”

The study comes with a $10 million milestone payment from AbbVie, and topline results are expected in early to mid-2017.

Galapagos has other drugs being tested in the clinic, including the potentiator molecules GLPG1837 and GLPG2451, and the corrector GLPG2222.

In previous tests, triple combinations of CF drugs in the companies’ portfolio have been shown to restore healthy CFTR levels in cultures of human bronchial epithelial (HBE) cells of CF patients carrying the F508del mutation in the CFTR gene. These combinations resulted in an increase in chloride transport (signaling activation of the CFTR) compared to Orkambi (ivacaftor and lumacaftor) in the cell cultures, Galapagos reported in its release.


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