CTP-543 maintains hair regrowth in adults with hair loss

Adults with moderate-to-severe alopecia areata (AA) had sustained or improved hair regrowth with the oral Janus kinase (JAK) inhibitor CTP-543, results of an open-label extension (OLE) study suggest.

“[While a] majority of our data are based on the 12-mg BID dosing, [our findings show that] treatment with CTP-543 8 mg BID or 12 mg BID … continues to be generally well-tolerated with adverse events (AEs) consistent with those observed in phase II studies. SALT* scores show continued maintenance of hair regrowth across the OLE,” said Dr James Cassella of Concert Pharmaceuticals, Lexington, Massachusetts, US, who presented the findings.

JAK signalling has been implicated in the pathophysiology of AA. As such, the investigators sought to determine the potential of JAK inhibition in AA. A total of 152 patients completing 24 weeks of treatment from three** phase II trials rolled over into the OLE and received daily CTP-543 8 mg BID or 12 mg BID. [EADV 2020, abstract 3085]

Stable, consistent responses

“We carefully monitored haematologic parameters because CTP-543 is a JAK inhibitor,” noted Cassella. Haemoglobin values with the 12-mg dose across the OLE were stable. The consistency and steadiness of responses were also seen in platelet and neutrophil counts.

There were 23 treatment discontinuations, three of which due to AEs. The most common AEs (ie, nasopharyngitis, acne, headache) were consistent with those observed in the phase II trials. A majority (76 percent) of the AEs were mild, while 21 percent were moderate. Two serious AEs (SAEs) may be treatment-related, while three were unlikely related to treatment. “[The] SAEs are generally sporadic in nature. Some are possibly related to the drug; some may be related to the mechanism of action,” said Cassella.

One of the notable things, as per Cassella, is the very consistent AE pattern observed in both the phase II trials and the OLE phase after seeing patients for another 6 or 9 months. “[For instance, the] nasopharyngitis – this is one of the more common things associated with JAK inhibition; [however, it is] relatively benign.”

“I think [this is] the most important take-home message – we are not seeing an emergence of a growing AE profile and we are seeing relative stability of the laboratory parameters that [may] be involved with JAK inhibition,” underscored Cassella.

Of note as well is the possible cessation of hair regrowth once treatment stops. “It has been the general thinking that, at some point, with JAK inhibitors, you will lose your hair if you stop treatment,” noted Cassella. “Surprisingly, for the few dose interruptions we had to have … we have not seen any hair loss [for] up to 3 weeks. [Also, once patients are] back on the drug, the hair response continues,” he added, noting that they will continue to probe further into this issue.

Sustained, improved efficacy

AA is a chronic, poorly treated disorder that may be tied to other autoimmune conditions, as well as anxiety and depression. In this study, the average duration of hair loss ranged between 3 and 4 years, and participants had high mean baseline SALT scores (ie, 85–90). “The higher the SALT score, the more scalp hair loss there is. [Therefore, our] patients had a significant amount of hair loss.”

Yet, SALT scores were either maintained, or improved with the 12-mg dose, with scores gradually dropping to 30–50 towards week 24 in the phase II trials. The response was consistent at 6 months, reflecting the remarkable stability of hair regrowth with CTP-543, noted Cassella. “[The] continuation of regrowth and improvement in SALT scores reflect a nice progression of hair regrowth.”

An improved response was seen among participants from one of the phase II trials who escalated from the 8-mg to the 12-mg dose. While these were not as deep as those seen with those who have been receiving 12 mg, the responses were nice nonetheless, said Cassella. “[Apart from the] continued response over time, there was an improvement, as patients were on the 12-mg dose for a longer period of time.”

“[Given the scarcity of treatment options for AA, the] good safety and continued stability of hair regrowth in the OLE are very encouraging. [Our] results support continued long-term dosing and evaluation of CTP-543,” concluded Cassella.