Patients with chronic spontaneous urticaria see well-controlled disease with briquilimab

Key takeaways:

• Briquilimab targets c-Kit to address mast cell diseases.
• Patients saw substantial reductions in tryptase as early as week 1.
• 100% of patients with a single 240 mg dose had complete response at week 8.

Patients with chronic spontaneous urticaria experienced substantial reductions in hives and itch with briquilimab through 16 weeks of treatment, with responses as early as week 1, according to an online presentation by Jasper Therapeutics.

“Chronic urticaria affects people of all ages across the world and is frequently associated with significant disease burden that goes beyond the effects on the skin,” Edwin Tucker, MD, chief medical officer of Jasper Therapeutics, told Healio.

Treatment need, mechanics

Approximately a third of patients with chronic spontaneous urticaria (CSU) have at least one symptom not related to the skin, including recurrent and unexplained fever; joint, bone and muscle pain; and/or malaise, Tucker continued.

Edwin Tucker

“The full impact of the disease goes beyond its physical symptoms, leading to reduced quality-of-life and mood-related comorbidities, with more severe disease and poor disease control associated with greater adverse social and emotional impacts,” he said.

Patients have called the swelling, itch and pain in CSU the worst aspects of the disease, Tucker said, along with feeling tired, irritable or weak as well as feeling a loss of control over their lives.

Additionally, patients noted the unpredictability of the attacks, social restrictions, feeling embarrassed, time away from work, restrictions on food or clothing, side effects of treatments and being unable to relax or sit.

“Surveys have also shown that patients experience significant levels of mental and physical impairment, anxiety and depression,” Tucker said.

Current treatment targets the symptoms of mast cell dysfunction. Approved options include second-generation H1-antihistamines and targeted biologic therapy. Off-label options include high doses of second-generation H1-antihistamines, immunosuppressive therapy, and antagonists for leukotriene receptors.

“For a large proportion of patients, these approaches are insufficient, and it’s common for patients to abandon treatment despite reporting high disease burden,” Tucker said.

“Briquilimab has the potential to improve upon these therapies by delivering superior efficacy via a mechanism of action that can deplete mast cells, the perpetrating cell in CSU,” he continued.

As a novel antibody therapy, briquilimab blocks c-Kit signaling, potentially depleting mast cells, which drive diseases such as chronic spontaneous urticaria, chronic inducible urticaria and asthma.

“Briquilimab has the potential to address the substantial portion of patients that do not respond to existing treatment options,” Tucker said.

Preliminary data from the BEACON trial that demonstrate deep and durable responses among patients with moderate to severe CSU who were intolerant of or refractory to prior treatment support these points of differentiation, he said.

Study design, results

The randomized, double-blind, placebo-controlled, phase 1b/2a BEACON trial included adults with moderate to severe CSU who were refractory to treatment with antihistamines and who could not tolerate omalizumab (Xolair; Genentech, Novartis), which is a biologic that targets IgE.

Patients had been diagnosed with CSU at least 6 months prior to enrollment. They also had Urticaria Activity Scores over 7 days (UAS7) of 16 or higher.

Doses included 80 mg (n = 8), 120 mg (n = 6) and 180 mg (n = 10) once every 8 weeks; 120 mg (n = 6) and 180 mg (n = 9) once every 12 weeks; and 240 mg (n = 4) and 360 mg (n = 4) given once. Twelve patients received a placebo.

Also, three patients received 10 mg doses and three more received 40 mg doses at weeks 0, 4, 12, and 20 in an open-label arm of the study.

Mean baseline UAS7 scores included 27.9 for those patients on 120 mg doses, 25.9 for those patients on 180 mg doses, 26.6 for those patients on 240 mg doses and 28.6 for those patients on placebo.

“We are extremely encouraged by the preliminary results of the BEACON study in chronic spontaneous urticaria,” Tucker said, adding that these findings indicated “rapid, deep and durable symptom control.”

At week 8, the 240 mg group had a mean change of –26.6 from baseline in UAS7 scores, compared with –12.4 for the placebo group.

Mean changes from baseline in UAS7 scores at week 12 included –9.3 for the 80 mg group, –27.2 for the 120 mg group, –13.2 for the 180 mg group and –9.2 for the placebo group.

At week 16, mean changes from baseline included –29.8 for the 120 mg group, which Tucker called a “dramatic” reduction, –21.7 for the 180 mg group, and –10.1 for the placebo group.

Percentages of patients who achieved complete response, defined as a UAS7 score of 0, included 100% of the 240 mg group and 16.7% of the placebo group at week 8; 16.7% of the 80 mg group, 50% of the 120 mg group, 28.6% of the 180 mg group and 8.3% of the placebo group at week 12; and 50% of the 120 mg group, 57.1% of the 180 mg group and 16.7% of the placebo group at week 16.

Overall, 50% or more of the patients who received multiple-dose regimens achieved well-controlled disease, defined as a UAS7 score of 6 or less, at 4 weeks, with 100% of the 240 mg group and 25% of the placebo group showing well-controlled disease at week 8.

At week 12, percentages of patients who achieved well-controlled disease included 33.3% of the 80 mg group, 75% of the 8-week 120 mg group, 42.9% of the 8-week 180 mg group, 66.7% of the 240 mg group and 8.3% of the placebo group.

Percentages of patients who achieved well-controlled disease at week 16 included 75% of the 12-week 120 mg group, 57.1% of the 12-week 180 mg group and 25% of the placebo group.

Also, all the patients who received a single 240 mg dose achieved a complete response by week 2 and maintained it through week 8. At week 12, 66% of them still had well-controlled response.

The study also tested serum tryptase for all participants, with means at baseline within the normal range, according to the researchers. There were substantial reductions as early as week 1 that correlated with the onset of clinical responses.

Specifically, 86% of the 8-week 180 mg group had tryptase levels below the lower limit of quantification at week 2, and 100% of the 240 mg group had tryptase levels below the lower limit of quantification at week 1.

Further, preliminary data indicate that the pharmacokinetic responses of the treatment groups were comparable with historical data for healthy volunteers.

The 240 mg dose had a time to maximum concentration of 4 to 7 days and a half-life of approximately 9 days. The researchers did not predict any accumulation with 240 mg doses administered every 8 weeks.

Anti-drug antibodies had an incidence rate of 34% with no clinically meaningful effect on briquilimab’s pharmacokinetics in these patients, the researchers also noted.

The researchers classified briquilimab’s use as well tolerated with a favorable safety profile, with 70.3% in the pooled treatment groups and 66.7% in the placebo groups reporting any treatment-emergent adverse events.

One patient in the 8-week 180 mg group reported a serious treatment-emergent adverse event and hypersensitivity, which led to discontinuation. One patient in the 12-week 180 mg group developed unrelated neutropenia, and one in the placebo group developed bronchitis.

Events possibly related to the c-Kit blockade included four patients in the treatment group and one in the placebo group with hair color changes; one in the placebo group with skin discoloration; six in the treatment group with taste change; and three in the treatment group and one in the placebo group with neutropenia.

Generally, the researchers said, these were low-grade events, with most resolving during repeat dosing and none leading to discontinuations or dose delays.

Two patients in the treatment group experienced grade 1 decreased neutrophil counts that resolved before the next dose, with no associated fevers or infections. Generally, the researchers said, neutrophil counts were stable. Reductions were predictable with subsequent recovery, with no discontinuations or dose delays.

Conclusions, next steps

Based on these findings, the researchers said that patients with moderate to severe CSU achieved rapid, deep and durable responses with briquilimab that were well tolerated.

Tucker said that these results were not surprising.

“But these results are significant in part because they support the potential for an optimal biologic dosing strategy with briquilimab to deliver robust efficacy along with favorable safety by allowing for recovery of other c-Kit expressing cells beyond mast cells between doses,” he said.

Briquilimab’s 9-day half-life and other unique attributes enable this strategy, Tucker said, adding that most of the adverse events potentially related to c-Kit blockade in the study were infrequent and resolved before the next dose.

“This contrasts with data generated by other anti-c-Kit antibodies in development which do not show resolution of side effects while on drug,” Tucker said.

The study will continue to dose and assess patients for safety and tolerability and for clinical efficacy. An open-label extension study will roll over patients from the BEACON study who have completed their follow-up period to 8-week 180 mg doses.

Jasper Therapeutics also has submitted 8-week 240 mg and 8-week 180 mg cohorts, which also will receive 240 mg induction doses, for regulatory review.

The company expects to begin registering patients with CSU for a phase 2b study in the second half of 2025, with doses based on data from the open-label extension and from additional BEACON cohorts with a 360 mg single dose, an 8-week 240 mg dose and an 8-week 180 dose after 240 mg loading doses. Phase 3 studies are planned as well.

“More immediately, we look forward to presenting additional data from the BEACON study at the American Academy of Allergy, Asthma & Immunology Annual Meeting in February,” Tucker said.

Beyond CSU, Jasper Therapeutics believes that briquilimab could address other chronic and mast cell-driven diseases with unmet treatment needs such as chronic inducible urticaria, asthma, COPD, chronic rhinosinusitis with nasal polyps, prurigo nodularis, atopic dermatitis, eosinophilic esophagitis, irritable bowel syndrome and food allergy.

“We are currently conducting a clinical study in patients with asthma, where we believe briquilimab could have impact across respiratory diseases driven by mast cells,” Tucker said.

Reference:

• Jasper Therapeutics reports positive data from BEACON study of briquilimab in chronic spontaneous urticaria. https://ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-reports-positive-data-beacon-study. Published Jan. 8, 2025. Accessed Jan. 8, 2025.