LEXINGTON, Mass.—As many as 650,000 Americans may suffer from alopecia areata, an autoimmune disease that results in partial or complete loss of hair on the scalp and body—often patchy loss. The disease, which can occur throughout life, affects both women and men, causing serious psychological consequences, including anxiety and depression.
Because there are currently no drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of the condition, the FDA selected it as one of eight new disease areas of focus under the Patient-Focused Drug Development Initiative (PFDDI) in 2016-2017.
Concert Pharmaceuticals Inc. has achieved initial positive Phase 2a interim data, demonstrating statistically significant results for the 8 mg twice-daily dose compared to placebo from its Phase 2 trial with CTP-543 for alopecia areata. Concert’s DCE (Deuterated Chemical Entity) platform is built around known drug structures, but substitutes deuterium for hydrogen to achieve “game-changing” enhancements in drug compounds and create novel small-molecule drugs, according to Dr. Roger Tung, co-founder, president and CEO of the company.
“The DCE technology platform selectively replaces certain hydrogen atoms with deuterium to provide, in favorable cases, better pharmacokinetic or metabolic properties, and thereby enhances clinical safety, tolerability or efficacy,” Tung explained. “While deuterium substitution has the potential to alter a compound’s metabolism in humans, now demonstrated in a number of clinical studies, it typically does not alter its potency, selectivity or general physical or chemical properties. As a result, when a drug is known to provide pharmacological benefits in humans, we have high confidence that the deuterium-substituted compound will provide similar actions. This often allows us to determine proof of concept for our technology in early-stage clinical evaluation (Phase 1) rather than waiting for later-stage trials to see if the compound has promise as a drug.”
He added, “We are hoping to find a cure for this devastating and poorly treated autoimmune disease. AA, a chronic condition, affects women, men and children of all ages. The disease profoundly impacts patients, and there are no FDA-approved treatment options to date. CTP-543 has the potential to be the first FDA-approved oral treatment for alopecia areata. We have generated the first double-blind, placebo-controlled, dose-ranging data demonstrating its effect in hair regrowth and its associated safety profile.”
The FDA has granted Fast Track designation for CTP-543, which was discovered by applying Concert’s deuterium chemistry technology to modify ruxolitinib, a drug that selectively inhibits Janus kinases 1 and 2 (JAK1 and JAK2). It is commercially available under the name Jakafi for the treatment of certain blood disorders. Deuterium modification of ruxolitinib was found to alter its human pharmacokinetics in ways that could enhance its use as a treatment for alopecia areata, according to Tung.
Concert was one of the first companies to utilize deuterium as a drug development tool, and has built a strong intellectual portfolio and platform around the approach. Tung, previously a founding scientist at Vertex, independently developed the approach and was Concert’s scientific founder. Because Concert’s new chemical entities are deuterated version of existing or validated drugs, they are expected to have a high probability of clinical success and achieve early clinical proof of concept, Tung explained.
The clinical trial for CTP-543 met the primary efficacy endpoint in the 8 mg twice-daily cohort, with 47 percent of patients achieving a ≥ 50-percent relative reduction in their overall severity of alopecia tool (SALT) score from baseline compared to placebo. For the 4 mg cohort, 21 percent of patients achieved a ≥ 50 percent relative reduction in their overall SALT score from baseline. In the primary analysis, the response observed in the 8 mg twice-daily dose was significantly different than the 4 mg twice-daily dose. The average baseline SALT score across all patients enrolled in the trial was approximately 88.
In the clinical trial, patients treated with an 8 mg twice-daily dose of CTP-543 met the primary efficacy endpoint vs. placebo at 24 weeks. Starting at week 12, significant differences from placebo were observed beginning at this dose. Hair regrowth did not seem to plateau at week 24. Treatment with CTP-543 was generally well tolerated, with the most common side effects being headache, upper respiratory tract infection, cough, acne and nausea. There were no serious adverse events reported.
Dosing in a 12 mg twice-daily cohort is currently underway. Complete study results are expected to be presented at a future medical meeting. Concert intends to discuss complete Phase 2a results and a development plan with the FDA in 2019, Tung said, adding “Given the size of the market opportunity, we believe alopecia areata represents a blockbuster market opportunity.”