A new treatment for chronic inducible urticaria (CindU), briquilimab, has shown encouraging results in early-stage clinical trials, with many patients experiencing partial or complete responses within just six weeks. The treatment also demonstrated a favorable safety profile, offering hope for individuals with this debilitating skin condition, which can severely impact quality of life.
Edwin Tucker, MD, MRCP, chief medical officer at Jasper Therapeutics, emphasized the significance of the findings during an online presentation. He explained that CindU, which often results in chronic hives and swelling, can be catastrophic for patients, especially in severe cases that affect not just the skin, but also other organs, including the airway.
“Chronic inducible urticaria is a debilitating condition of the skin, and in severe subtypes, involves other organs, including the airway, which can be life-threatening,” Tucker said. “There are currently no approved treatments beyond antihistamines for CindU, and this represents a significant unmet medical need.”
The Role of Mast Cells in CindU
CindU is characterized by the activation of mast cells, which release inflammatory mediators that lead to symptoms such as hives and swelling. This immune system dysfunction causes physical, psychological, and social impacts, leaving many patients with few treatment options.
Briquilimab, a novel therapy developed by Jasper Therapeutics, aims to address this gap by targeting mast cells. By depleting these cells, briquilimab may reduce disease severity and improve patients’ quality of life, Tucker explained.
SPOTLIGHT Study: Early Data Shows Positive Results
The Phase 1b/2a SPOTLIGHT study is currently enrolling adults with symptomatic dermographism and cold urticaria who have not responded to antihistamines. Participants in the study receive a single subcutaneous dose of briquilimab, followed by a 12-week observation period to assess efficacy and a 24-week period to monitor safety.
As of the latest update, 15 patients have been enrolled, with three receiving a 40 mg dose and 12 receiving a 120 mg dose. The mean age of participants in the 40 mg group was 35.3 years, while those in the 120 mg group had a mean age of 46.4 years. Most participants had symptomatic dermographism, with a smaller group affected by cold urticaria.
Baseline measurements showed that patients were severely affected by their condition, with average Urticaria Control Test (UCT) scores of 3.7 for the 40 mg group and 6.3 for the 120 mg group. This suggests significant disease activity upon entry into the study.
Positive Clinical Responses
At the six-week mark, briquilimab demonstrated a rapid and significant clinical effect. In the 40 mg group, one patient achieved a complete clinical response, while the other two had a partial response. In the 120 mg group, three patients with cold urticaria and seven with symptomatic dermographism reached complete clinical responses, and one patient experienced a partial response.
Overall, 93% of participants (14 out of 15) showed a clinical response within the first six weeks, highlighting the potential efficacy of briquilimab as a treatment for CindU. Additionally, patients showed a significant decrease in tryptase levels—a marker of mast cell activity—starting as early as day seven post-treatment. This drop in tryptase levels remained well below baseline through the six-week observation period, correlating with clinical improvement.
By the second week, 11 out of 12 patients in the 120 mg group had a partial or complete response based on tryptase levels. By the six-week follow-up, six patients maintained a complete response, while one continued to experience a partial response. Ten patients from the 120 mg cohort also achieved a UCT score of 12 or higher, indicating well-controlled or completely controlled disease.
Safety and Tolerability
Briquilimab was generally well tolerated, with no serious adverse events reported. The most common side effects were mild, including fatigue, dizziness, headache, nasopharyngitis, and muscle-related symptoms. Notably, the drug did not cause any hypersensitivity reactions or lead to treatment discontinuation.
Two patients in the 40 mg group and 10 in the 120 mg group experienced adverse events, but all were graded as mild or moderate (Grade 1 or 2). There were no significant changes in hair or skin color, and no infections or severe neutropenia were observed. The mild elevations in creatine kinase levels were noted in two patients, but these were considered non-concerning.
Tucker emphasized that the treatment was well tolerated overall, with no discontinuations due to safety concerns. “The rapid onset of clinical responses, combined with minimal adverse effects, highlights the potential of briquilimab as a transformative treatment for CindU,” he said.
Future Directions
Jasper Therapeutics has expanded the study to include a cohort of patients receiving 180 mg doses of briquilimab. Full data from the study is expected to be presented in the first half of next year.
Ronald Martell, CEO of Jasper Therapeutics, explained that briquilimab’s relatively long half-life of nine days could help achieve sustained clinical responses, with patients potentially requiring less frequent dosing. “This allows for clinical improvement shortly after treatment, with the drug washing out before symptoms return, enabling redosing before symptom recurrence,” he said.
As the SPOTLIGHT study progresses, the potential for briquilimab to become a groundbreaking therapy for chronic inducible urticaria continues to grow. If these early results are confirmed, briquilimab could offer a much-needed solution for patients suffering from this challenging condition.
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