Patients with chronic inducible urticaria see complete response to briquilimab at 6 weeks
Key takeaways:
- Briquilimab depletes the mast cells that release inflammatory mediators.
- Patients reported improvements in TempTest and FricTest scores at 6 weeks.
- The safety and tolerability profile was favorable.
Patients with chronic inducible urticaria experienced partial or complete response to briquilimab in 6 weeks with a favorable safety and tolerability profile, according to an online presentation by Jasper Therapeutics.
These patients have a “high unmet medical need,” Edwin Tucker, MD, MRCP, chief medical officer at Jasper Therapeutics, said during the presentation.
“Chronic inducible urticaria is a debilitating condition of the skin, and in severe subtypes, involves other organs, including the airway, which is going to be catastrophic for certain patients,” Tucker said.
Mast cells are central to the disease’s pathophysiology of chronic inducible urticaria (CindU), Tucker said, as deep granulation leads to the release of inflammatory mediators and subsequent symptoms.
“For most patients with CindU, physical, social and psychological impacts are significant impairments to quality of life,” he said. “Beyond antihistamines, there are no approved treatments available globally for patients with CindU.”
By depleting mast cells, Tucker said, briquilimab may offer a new treatment paradigm that reduces disease burden and improves quality of life.
The SPOTLIGHT study
The phase 1b/2a SPOTLIGHT study is enrolling adults with symptomatic dermographism and cold urticaria who are refractory to antihistamines. Patients will receive a single subcutaneous dose of briquilimab, followed by a 12-week efficacy observation period and then a 24-week safety observation period.
So far, the researchers have enrolled three patients who received a 40 mg dose (mean age, 35.3 years; one woman) and 12 patients who received a 120 mg dose (mean age, 46.4 years; eight women).
The 40 mg group included one patient with cold urticaria and two patients with symptomatic dermographism. The 120 mg group included four patients with cold urticaria and eight patients with symptomatic dermographism.
Also, the 40 mg group had a mean TempTest score of 16°C, a mean FricTest score of 3.5 and mean tryptase of 4.7 ng/mL. Means for the 120 mg group included 20.8°C for the TempTest, 3.9 for the FricTest and 7.6 ng/mL for tryptase.
“This is as expected, as these patients were refractory to their antihistamines prior to enrolling in the study,” Tucker said.
Mean Urticaria Control Test (UCT) scores, with 12 indicating well controlled disease and 16 indicating complete control on a 16-point scale, included 3.7 for the 40 mg group and 6.3 for the 120 mg group.
“These UCT scores at baseline reiterate the severity of the patients’ disease upon enrolling into the study,” Tucker said.
At 6 weeks, the researchers considered no response at Fric Level 4 to be complete response to treatment and an improvement of two pins or more a partial response. Also, they considered a negative TempTest at 4°C or lower to be complete response and a 4°C or more improvement to be a partial response.
One patient with symptomatic dermographism in the 40 mg group achieved a complete clinical response, and the other two patients achieved a partial response.
In the 120 mg group, three patients with cold urticaria and seven patients with symptomatic dermographism achieved a complete clinical response, and one patient with symptomatic dermographism had partial response.
“When combining both the 40 mg and the 120 mg cohorts, we saw 14 out of 15 participants, or 93% of participants, achieve a clinical response in the 6-week observation period,” Tucker said.
Patients also experienced a rapid fall in tryptase levels during their first post-dose visit at day 7, and these levels remained well below baseline values through 6 weeks, Tucker said.
“The rapid decline in tryptase, consistent with mast cell biology and c-Kit blockade, and seen in other studies, correlates with the rapid onset of clinical response,” Tucker said.
By week 2, 11 of 12 patients in the 120 mg group achieved a partial or complete response based on tryptase levels. By week 6, six of these 12 maintained complete response, and one maintained a partial response.
“We will continue to assess the durability of these clinical responses as we complete the trial,” Tucker said.
At day 29, 10 of these 12 patients also achieved a UCT score of 12 or higher, indicating well controlled or compete control of the disease.
Two patients in the 40 mg group and 10 in the 120 mg group experienced adverse events. Adverse events reported by two or more patients included fatigue, dizziness, headache, nasopharyngitis, increased blood creatine kinase (CK), diarrhea, muscle tightness and nausea.
“All were grade one or two,” Tucker said. “The CK elevations noted in two participants were mild, and alternative causes were noted.”
Two patients experienced grade one neutropenia, and both resolved.
Tucker described treatment as “well tolerated, with no discontinuations due to safety.”
None of the adverse events were serious. There were no hypersensitivity reactions or adverse events leading to discontinuation or death. Also, there were no changes in hair or skin color.
Additionally, the researchers did not observe any absolute neutrophil counts below 1,500 cells/µL through 6 weeks, nor were there any associations with infection. The decreases in absolute neutrophil counts that did occur resolved without clinical sequelae.
“Taken together, these results presented from the SPOTLIGHT trial, with minimal impact on neutrophil counts, with high levels of rapid clinical response, demonstrate the potential of briquilimab,” Tucker said.
Next steps
“These attributes, along with briquilimab’s 9-day half-life, should allow patients to achieve clinical response shortly after treatment, then have the drug wash out, allowing the return of c-Kit signaling, followed by redosing prior to the return of symptoms,” Ronald Martell, CEO of Jasper Therapeutics, said during the presentation.
The company has now added a cohort of patients receiving 180 mg doses.
“We expect to present the full data from the study in the first half of next year,” Martell said.