Concert Pharmaceuticals, Inc. (NASDAQ: CNCE) today announced positive topline data from a Phase 1 multiple ascending dose clinical trial of CTP-656. CTP-656 is a novel deuterium-modified version of ivacaftor. Ivacaftor is commercially available under the name Kalydeco®. The clinical trial results continue to support the development of CTP-656 as a once-daily potentiator for the treatment of cystic fibrosis patients with certain gating mutations. In addition, CTP-656 demonstrated enhanced exposure to the parent drug and less exposure to metabolites after repeat dosing, confirming its differentiated metabolite profile relative to Kalydeco. Results of the Phase 1 trial also showed that CTP-656 was well-tolerated and its safety profile was comparable to that of Kalydeco. The Company expects to present the Phase 1 multiple ascending dose results at the 39 th European Cystic Fibrosis Conference being held June 8-11, 2016 in Basel, Switzerland.

"We are pleased with the profile of CTP-656 emerging from the Phase 1 program," said James Cassella, Ph.D., Chief Development Officer of Concert Pharmaceuticals. "We believe its potential to be dosed once-daily as well as its improved metabolite profile may provide important patient benefits, including ease of adherence and potentially improved efficacy."

This Phase 1 trial was conducted in two parts and enrolled 38 healthy volunteers to assess safety, tolerability and pharmacokinetics of CTP-656 in a tablet formulation. The first part assessed a single dose pharmacokinetic comparison of 150 mg of CTP-656 versus 150 mg of Kalydeco. The second part assessed three doses of CTP-656, 75 mg, 150 mg and 225 mg, dosed daily for seven days compared to placebo. Clinical highlights from Part 2 include:
  • Pharmacokinetics. Across all doses, the average plasma half-life of CTP-656 was approximately 18 hours at steady state. CTP-656 showed a dose-proportional increase in exposure with repeated dosing for the 75 mg and 150 mg doses. The 225 mg dose group showed higher than dose-proportional exposure.
  • Metabolite Profile. The metabolite exposure profile of CTP-656 after seven days of dosing in the tablet formulation showed the greatest exposure in plasma was to parent drug. These findings confirmed that at steady state the metabolite profile was similar to the profile previously demonstrated in the single ascending dose Phase 1 trial.
  • Safety. There were no serious adverse events and the safety profile of CTP-656 has been comparable to that of Kalydeco.

Dr. Cassella added, "We believe that we have identified a safe and well-tolerated dose range for CTP-656 that will provide effective clinical CFTR potentiation. Importantly, we believe we have the necessary data to select the doses for our Phase 2 trial that bracket parent drug exposure associated with the commercial dose of Kalydeco."

The Company previously reported positive results from Part 1 of this Phase 1 clinical trial in which a single-dose tablet formulation of CTP-656 was compared to the commercial tablet formulation of Kalydeco. The results from this trial confirmed CTP-656's superior pharmacokinetic profile to Kalydeco as was previously reported from Concert's single ascending dose trial, in which CTP-656 was dosed as an aqueous suspension. In that trial, CTP-656 demonstrated favorable pharmacokinetic properties including a longer half-life, reduced rate of clearance, substantially increased exposure and greater plasma levels at 24 hours.

Concert recently completed a Phase 1 trial to evaluate the bioavailability and pharmacokinetics of CTP-656 when dosed fasted, or with a low fat or medium fat-containing meal, in healthy volunteers. Results from this study showed that CTP-656's exposure was consistent when dosed with either a low or moderate fat-containing meal and was also consistent with exposure previously observed when dosed with a high fat meal.

"We are pleased to see that full bioavailability of CTP-656 was retained even with a low fat meal," stated Dr. Cassella.

About CTP-656 and Cystic Fibrosis

CTP-656 is a novel potentiator that may enable once-daily dosing that was developed by applying deuterium chemistry to modify ivacaftor. Concert is initially developing CTP-656 as a potential monotherapy treatment for cystic fibrosis due to gating mutations of the gene that encodes for cystic fibrosis transmembrane conductance regulator (CFTR), a protein, which regulates components of sweat, mucus clearance and digestion. Cystic fibrosis is a life-threatening, hereditary genetic disease that has systemic effects and can cause significantly reduced lung and digestive system function. According to the Cystic Fibrosis Foundation, an estimated 70,000 people worldwide have cystic fibrosis.

About Concert

Concert Pharmaceuticals is a clinical stage biopharmaceutical company focused on applying its DCE Platform® (deuterated chemical entity platform) to create novel small molecule drugs. This approach starts with approved drugs, advanced clinical candidates or previously studied compounds that have the potential to be improved with deuterium substitution to enhance clinical safety, tolerability and efficacy. The Company is developing a broad pipeline targeting CNS disorders, genetic diseases, and inflammatory diseases. For more information, please visit

Cautionary Note on Forward Looking Statements

Any statements in this press release about our future expectations, plans and prospects, including statements about clinical development and success of CTP-656 and other statements containing the words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would," and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, expectations for regulatory approvals and other factors discussed in the "Risk Factors" section of our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission and in other filings that we make with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent our views only as of the date of this release and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update any forward-looking statements included in this press release.

Concert Pharmaceuticals Inc., the CoNCERT Pharmaceuticals Inc. logo and DCE Platform are registered trademarks of Concert Pharmaceuticals, Inc.

Kalydeco is a registered trademark of Vertex Pharmaceuticals, Inc.

View source version on

Copyright Business Wire 2010