FDA Grants Orphan Drug Status to CF Therapy Now in Phase 2 Study

Patrícia Silva, PhD avatar

by Patrícia Silva, PhD |

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Cystic fibrosis treatment

The U.S. Food and Drug Administration (FDA) has designated Concert Pharmaceuticals‘ next-generation therapy, CTP-656, an Orphan Drug to treat cystic fibrosis (CF).

CTP-656 is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that, according to the company’s website, was developed by applying deuterium chemistry to modify Kalydeco (ivacaftor).  Concert has said CTP-656 is a potential monotherapy for CF associated with gating mutations of the gene encoding the CFTR protein, which regulates sweat, mucus clearance and digestion. (CFTR is the gene that is defective in CF patients.)

The FDA’s designation coincides with a randomized, parallel-group, double-blind, placebo-controlled Phase 2 clinical trial (NCT02971839) to evaluate CTP-656 in patients with gating mutations. The study, which is recruiting participants, is evaluating the safety and effectiveness of CTP-656 with an open-label active comparator (Kalydeco) and a placebo. Results are expected this year.

“Receiving orphan drug designation is an important regulatory milestone, and we are pleased that CTP-656 for cystic fibrosis has been granted this status,” Roger Tung, PhD, president and chief executive officer of Concert Pharmaceuticals, said in a press release. “We are developing CTP-656 to potentially offer advantages over standard of care, and our team is committed to advancing the clinical development program to address the unmet needs of individuals with cystic fibrosis.”

Orphan Drug designation helps companies develop products for rare diseases (those that affect fewer than 200,00 people in the U.S.) by giving them incentives such as tax credits or exemption from FDA user fees, assistance in clinical trial design, and potential market exclusivity for up to seven years if the drug is approved.

Concert reported that results of a Phase 1 cross-over comparison showed CTP-656 had a superior pharmacokinetic profile to Kalydeco, including a reduced rate of clearance, longer half-life, substantially increased exposure and greater plasma levels at 24 hours.

Kalydeco, a CF treatment developed and commercialized by Vertex, is also a potentiator of the CFTR protein and was the first drug to address the underlying causes of MS instead of focusing on the symptoms. It was approved by the FDA in 2012 for adults and in 2015 for children older than 2. It is also available in Europe, Canada, Australia and New Zealand.

Patients with a CFTR mutation develop thick, sticky mucus in their respiratory, digestive, and reproductive systems, and Kalydeco acts to keep the CFTR proteins at the cell surface open to allow salt and water to move through the cells, improving hydration and mucus clearance.