Vertex, Concert Strike Deal on Investigational Therapy VX-561

Vertex Pharmaceuticals has made a $32 million purchase from Concert Pharmaceuticals related to future milestones from the 2017 agreement when Vertex purchased Concert’s investigational treatment for cystic fibrosis (CF), VX-561.

According to Roger Tung, PhD, Concert’s president and CEO, the purchase will help Concert as it continues clinical development of an experimental treatment for alopecia areata, which is a type of sudden hair loss caused by the immune system attacking hair follicles.

“This transaction provided an opportunity to secure non-dilutive capital [does not require giving up company ownership] and strengthens our balance sheet as we continue to advance CTP-543, our lead asset for alopecia areata, through its Phase 3 program,” Tung said in a press release. He added that the company’s current assets are expected to fund the company through mid-2022.

VX-561 — called CTP-656 when it was being developed by Concert, and also known as deutivacaftor — is an investigational CFTR potentiator.

The CFTR (cystic fibrosis transmembrane conductance regulator) protein normally functions like a “gate” at the surface of cells, allowing salts to flow in and out of the cell. People with CF have mutations in the gene providing instructions to make this protein, resulting in the production of thick mucus that clogs the airways and impairs other organs.

As a CFTR potentiator, VX-561 aims to keep the “gate” of the protein open, which is useful for people with certain mutations that cause it to be “stuck closed.” Vertex markets a CFTR potentiator called Kalydeco (ivacaftor), which is widely approved to treat people with CF caused by certain mutations.

Vertex has sponsored two Phase 2 clinical trials (NCT03224351 and NCT03227471) that tested VX-561, in combination with other CF therapies, in patients with one F508del mutation and one minimal function mutation.

In one of the trials, 19 participants received daily treatment with VX-561 in combination with the then-investigational medications VX-659 and VX-661, while six participants were given a placebo, for four weeks. Notably, VX-661, also called tezacaftor, is part of a combination therapy formulation called Symdeko (tezacaftor plus ivacaftor) that has been approved to treat some CF patients in the U.S. and Canada.

Results from the trial indicated that the combination treatment improved participants’ lung function, reduced sweat chloride levels, and improved quality of life.

The second trial tested VX-561 in combination with tezacaftor and the then-investigational VX-445, also called elexacaftor, which is part of Vertex’s approved triple-combination therapy Trikafta. In the trial, 21 participants were given the combination of therapies, while eight were given placebo, for four weeks.

Results from the second trial were similar to those from the first; treatment significantly improved lung function and reduced sweat chloride levels.

Both therapy combinations were generally well-tolerated. Commonly-reported adverse side effects in the trials included cough, infective pulmonary exacerbation, nausea, throat pain, fever, and rash.