Concert's alopecia drug sails through phase 2; phase 3 on deck for 2020

Concert Pharmaceuticals reported data from the highest dose of its alopecia drug tested in a phase 2 study, confirming its theory that it would outshine the middle dose—a level that made enough of a difference in alopecia symptoms that the company could have taken it forward into phase 3. 

The study tested 4 mg, 8 mg and 12 mg doses of Concert’s CTP-543 against placebo in 149 patients. The drug is a deuterated version of ruxolitinib, a JAK inhibitor marketed by Incyte in the U.S. as Jakafi.

Last November, the company announced results for the two lower doses after 24 weeks of treatment. Concert found that the 4 mg dose wasn’t “statistically different from placebo,” though it did lower patients' alopecia severity score by 50% or more, as measured by the severity of alopecia tool (SALT), in about one-fifth of patients. The 8 mg dose did better, reducing SALT scores by 50% or more in 47% of patients and meeting the study’s primary endpoint. 

While Concert expected the 12 mg dose to do even better, CEO Roger Tung told FierceBiotech at the time that the safety and efficacy seen at 8 mg were enough to take the drug forward at that dose level. 

As with the 8 mg dose, more patients on the 12 mg dose had a 50% or more reduction in their SALT score than patients taking placebo—58% versus 0%, the company said. Both dose groups had more patients who saw a 75% or greater or 90% or greater decrease in SALT score from baseline versus placebo. The average SALT score for all patients, where 0% is no scalp hair loss and 100% is total scalp hair loss, was 88%. Finally, 78% of patients on the 12 mg dose and 58% of patients taking the 8 mg dose rated their disease as “much improved” or “very much improved.” 

RELATED: Concert's alopecia drug hits phase 2 endpoint with more data to come

“Clearly, we see an improved response with the 12-mg dose group and we would go so far as to say that the 12 mg group sets a new bar for efficacy in this disease,” Tung told FierceBiotech.  

There is no approved treatment for alopecia areata, an autoimmune disease in which the immune system attacks hair follicles, causing hair to fall out in small patches. According to the National Alopecia Areata Foundation, current treatments are borrowed from other disease areas and may work for some people but not others. These include oral, topical and injected corticosteroids. 

“They’re not really long-term therapies for anyone,” Tung said. “The intralesional injections tend to be more effective. But they’re inconvenient and painful from what we hear from patients.” 

Because patients receive one injection for a small area of scalp, someone with a large area of hair loss would need many injections. 

“Those need to be repeated on a monthly basis. Really, no one tolerates them for any significant amount of time,” Tung said. 

Topical steroids come with their own problems. They tend to be less effective and can cause skin sensitivity or thinning of the skin. 

CTP-543 is an oral drug taken twice a day. The study tested it for 24 weeks, or six months, but Concert hasn’t gathered enough data to decide how long a treatment period should last. 

Concert started a long-term, open-label extension study into which patients in the 12 mg dose group can enroll. 

“We think six months is on the short end of what is going to define the efficacy of this compound and other compounds with similar mechanisms,” Tung said. “What we’re seeing as we go from week 12 to 16 to 20 to 24 is that the efficacy continues to climb over that time frame.” 

Although a twice-daily pill is a walk in the park compared to dozens of steroid injections, Concert has a pair of open-label phase 2 studies looking at once-daily doses. One is testing 16 mg once a day versus 8 mg twice a day and is due to read out by the end of the year. The second will compare 24 mg once a day to 12 mg twice a day and will have a good number of patients enrolled by then. 

Armed with these data, as well as the data announced Tuesday, the company plans to meet with the FDA in early 2020 to map out what its registrational program should look like. The goal is to kick off a phase 3 study later next year.