Concert Pharma, a biotechnology company utilizing deuterium chemistry to discover and develop innovative drug products that can address unmet medical needs, recently announced positive results from its Phase 1 single ascending dose study of investigational cystic fibrosis drug CTP-656.
CTP-656 is a novel, potentially disease-modifying treatment for cystic fibrosis. The drug is a deuterated analog of ivacaftor, which is known commercially as Kalydeco® and part of a fixed-dose combined treatment known as Orkambi — both developed by Vertex Pharmaceuticals. “Deuterated” drug analogs are variants where the ordinary isotope of hydrogen in the molecule is replaced with deuterium — a process that Concert believes can improve upon the original molecule in terms of therapeutic value.
Results from the Phase 1 study support the development of CTP-656 as a once daily monotherapy or in combination with other CFTR modulators for specific cystic fibrosis genotypes. Compared to Kalydeco, the current gold-standard treatment for CF, CTP-656 demonstrated a superior pharmacokinetic profile.
The results also revealed that CTP-656 was well-tolerated by the patients and also showed that its safety profile was similar to Kalydeco. These results were recently presented in Manchester, UK, during the 2015 Cystic Fibrosis Trusts UK Conference.
“CTP-656 is a new chemical entity that we designed to provide superior pharmacokinetic properties while leveraging the known safety and efficacy of Kalydeco. Based on data from our initial clinical evaluation, we are extremely pleased with the compound’s profile,” stated James V. Cassella, Ph.D., Chief Development Officer at Concert.
“With the favorable safety and pharmacokinetic profile of CTP-656 observed in our single ascending dose trial, we look forward to the completion of our Phase 1 multiple dose clinical evaluation and advancement of this drug candidate into a Phase 2 clinical efficacy study in 2016,” added Dr. Cassella. “We intend to develop CTP-656 to improve patient outcomes and expand therapeutic options as a potential single agent treatment, as well as to enable new combination medications so that patients with cystic fibrosis can have a range of treatment options.”
The trial aimed to assess the tolerability, safety and pharmacokinetics of CTP-656 in single ascending doses compared to a single dose of Kalydeco in ten healthy volunteers.
The researchers administered three doses of CTP-656 (75mg, 150mg and 300 mg) as an aqueous suspension.
In nine of the participants, the researchers also compared a 150 mg dose of CTP-656 to a 150 mg solid dose of Kalydeco. There were no tolerability or adverse events reported.
In terms of pharmacokinetics, CTP-656 was found to be superior to Kalydeco, with results showing a reduction in the clearance rate, longer half-life, increased exposure and greater levels of plasma after 24 hours.
Results from the metabolites analysis showed that the overall exposure profile of CTP-656 was different from Kalydeco and was due to parent drug, whereas with Kalydeco the plasma exposure was mainly due to a less-active metabolite and an equivalent amount of an inactive metabolite.
“We believe that the longer half-life and lower metabolite levels measured for CTP-656 are clear demonstrations of a positive deuterium effect and might offer a dosing advantage to the patient,” said Dr. Cassella.
Results from the Phase 1 study will be presented in a poster session during the 2015 North American Cystic Fibrosis Conference (October 8-10).
During the last trimester of 2015, the company is expecting to begin a new Phase 1 trial evaluating multiple ascending doses of CTP-656 in healthy volunteers. This new trial was include a comparison between a single dose of CTP-656 versus Kalydeco. The results from this study are expected to be disclosed during the first semester of 2016.