Bempikibart use led to clinically meaningful SALT improvements among those with alopecia areata in the phase 2a SIGNAL-AA study at 36 weeks.
In a new announcement by Q32 Bio, positive topline results have been released from the 36-week analysis of Part B of the company’s phase 2a SIGNAL-AA trial, with investigational drug bempikibart showing clinically meaningful levels of hair regrowth and a favorable safety profile among those with severe or very severe
The company’s release highlighted bempikibart’s design as a fully human monoclonal antibody targeting the interleukin-7 receptor alpha (IL-7Rα). Bempikibart was designed to modulate adaptive immune function via the inhibition of both IL-7 and thymic stromal lymphopoietin (TSLP) signaling.
"Alopecia areata is a complex, immune driven disease with limited therapeutic options,” Arash Mostaghimi, MD, MPA, MPH, associate professor of Dermatology and vice chair of Clinical Trials and Innovation for Brigham and Women's Hospital and Harvard Medical School, said in a statement.1 “The robust efficacy data in a population that includes JAK inhibitor-experienced patients, combined with a differentiated safety profile, demonstrate the potential for bempikibart to be a first-line treatment for alopecia areata.”
Enrollment in this open-label Part B analysis included 33 individuals showing baseline Severity of Alopecia Tool (SALT) scores ranging from 50 - 100. Additionally, they would have a current disease episode lasting no more than 4 years. The investigative team noted prior use by 36.4% of oral Janus kinase (JAK) inhibitors, indicating enrollment of a treatment-experienced population. According to the release, recruitment of subjects surpassed the company’s original target due to strong interest levels.
Participants received four weekly 200-mg loading doses followed by 200-mg subcutaneous injections every other week through Week 36. Investigators assessed changes in SALT scores as the primary efficacy endpoint, while additional analyses evaluated the proportion of patients reaching predefined thresholds of hair regrowth.
At Week 36, patients in the modified intent-to-treat (mITT) population experienced a mean 35.3% reduction in SALT scores from baseline. Additionally, 40.0% of patients in the mITT analysis achieved a SALT-20 response, indicating at least 80% scalp hair coverage, while 44.0% met both SALT30 and SALT50 response criteria. Comparable response rates in the overall intent-to-treat population were 30.3% for SALT-20 and 33.3% for both SALT30 and SALT50. Responses were observed among patients with both severe and very severe disease at study entry.
Encouraging early findings highlighting durability after drug discontinuation were also identified by the investigative team. During the ongoing off-treatment follow-up period, several of the study’s subjects maintained or continued to improve their responses, including a single individual who reportedly attained full scalp hair regrowth.
Safety data were described as consistent with previous bempikibart research. The company highlighted a lack of treatment-related serious adverse events (AEs) or grade 3 or higher treatment-related AEs. Injection-site reactions were the most common treatment-emergent AE, with 36.3% of participants reporting such a reaction. However, the reactions were described as generally isolated, mild in their level of severity, and having resolved without intervention. They also appeared in only 4% of all of the study’s administered doses.
Q32 Bio also noted favorable pharmacodynamic, pharmacokinetic, and immunogenicity results. The loading-dose strategy attained steady-state drug concentrations approximately 10 weeks earlier than those observed in Part A, whereas anti-drug antibody development continued to be negligible.
In addition to the Part B results, the company shared findings resulting from the completed open-label SIGNAL-AA Part A extension study. Eight individuals, including prior drug responders, non-responders, and those on placebo, reinitiated the therapy after remaining off the medication for 26 - 55 weeks.
Long-term treatment continued to demonstrate a favorable safety profile, with patients who entered the extension having maintained hair growth generally sustaining or further improving their responses. According to Q32 Bio, these findings support the potential value of maintenance dosing.
Recruitment of participants in the ongoing Part B extension study was described as continuing. The company also described plans to present the full Part B dataset at a future medical conference. It intends to advance bempikibart into a registration-directed clinical program within the first half of 2027.
"For patients and prescribers seeking an effective and safe alternative to JAK inhibitors, these findings are encouraging and merit further clinical advancement,” Mostaghimi said in his statement.1
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