touchDERMATOLOGY coverage from data presented at AAAAI/WAO 2025:
Mast cells are believed to play a central role in the pathogenesis of chronic spontaneous urticaria (CSU) and its common symptoms, itch and hives, making them a key therapeutic target.1 While H1-antihistamines and omalizumab provide relief for many patients, symptoms persist for a significant number.2
An emerging class of therapies with the potential to address this gap are c-Kit inhibitors, which directly target mast cells. These inhibitors are thought to work by blocking stem cell factor (SCF)/c-Kit signalling, essential for mast cell survival.
Briquilimab, an anti-c-Kit monoclonal antibody, is being investigated for its ability to selectively deplete mast cells and alleviate the symptoms of CSU. At this year’s American Academy of Allergy, Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress (San Diego, CA, USA; 28 February–3 March 2025), the initial results from BEACON (ClinicalTrials.gov identifier: NCT06162728), a phase Ib/IIa dose-escalation study of briquilimab in adults with CSU, were presented.3,4
To explore the latest study findings and, importantly, the potential of briquilimab as a novel treatment for CSU and other mast cell-mediated diseases, we spoke with study investigator Professor Thomas Casale (University of South Florida, Tampa, FL, USA) and Dr Ed Tucker (Chief Medical Officer, Jasper Therapeutics, San Francisco, CA, USA).
Q. Could you give us a brief overview of the current treatment paradigm for CSU?
Prof. Thomas Casale: For chronic spontaneous urticaria, the first-line treatment is going to be non-sedating antihistamines at their standard licensed doses. If that fails, the dosage can be increased up to four times the licensed amount. However, even at this higher dose, approximately 50% of patients will continue to experience symptoms.
Currently, the next step in treatment would be to use omalizumab, an anti-IgE [immunoglobulin E] monoclonal antibody. However, if patients don’t respond to omalizumab, there’s no clear-cut solution—we try various approaches, but none are highly studied or well-established. Cyclosporine is generally considered the next option, though the supporting clinical trials are not particularly strong.
Q. What is the rationale behind investigating briquilimab in the treatment of CSU?
Prof. Thomas Casale: The main rationale is that, while omalizumab is effective for many, it doesn’t work for everyone. Additionally, some patients experience a slow response to treatment. When dealing with chronic spontaneous urticaria, relief isn’t just important—it’s urgent. The faster, the better. That’s why I’m excited about this new particular agent: its onset of action is very rapid.
Q. What were the aims and design of the initial phase Ib/IIb study investigating briquilimab in CSU?
Dr Ed Tucker: Our goal was to address the unmet medical need, as Tom described. We enrolled patients who were refractory or intolerant to existing therapies, including antihistamines and omalizumab. The objective was to demonstrate that briquilimab, a monoclonal antibody targeting c-Kit, could deplete mast cells, alleviate symptoms such as hives and itch, and ultimately improve patients’ quality of life. Additionally, we aimed to assess the safety of this molecule in the study population and evaluate its pharmacokinetics.
The key point here is that mast cells play a central role in chronic spontaneous urticaria and acute urticaria, so a treatment like this, which essentially eliminates mast cells, goes straight to the heart of the problem and should provide a unique opportunity for a novel therapeutic avenue.
Prof. Thomas Casale: Building on Ed’s point, we measured serum tryptase levels in these patients, with tryptase being a key marker of mast cells. What we saw was a rapid and dose-dependent decrease in tryptase in the blood, which aligns with mast cell depletion and reinforces the potential of this therapy as a treatment for urticaria.
Q: How many patients were included in this initial analysis and what were their baseline characteristics?
Dr Ed Tucker: In this data cut, we are presenting results from 49 patients, with 37 receiving the active treatment and 12 on placebo. This includes multiple ascending dose cohorts, ranging from 10 milligrams to 240 milligrams. Some of those cohorts were multi-dose, particularly those in the 10 to 180 milligram cohorts.
We also tested dosing intervals between 8 and 12 weeks because, as Tom mentioned, we wanted to determine when mast cells actually return. Our goal here is to reduce mast cells while avoiding effects on other c-Kit-expressing tissues, which could lead to potential safety and tolerability concerns, such as changes in hair colour or taste.
Having a drug such as briquilimab, which has a rapid Tmax [time-to-peak drug concentration], high Cmax [maximum concentration], and clears from the system relatively quickly, allows the treatment to reduce mast cell levels while providing a period where other c-Kit-expressing tissues are not exposed to the drug, thus mitigating some of those potential safety concerns.
Q: What did the analysis of the study results reveal about the safety and tolerability of briquilimab?
Dr Ed Tucker: We are very pleased with the safety findings to date. The treatment-related adverse events in the active arms have been comparable to those in the placebo group. Overall, we have observed very limited numbers and low grades of adverse events that could be associated with other c-Kit-expressing tissues. The hair and skin colour changes, which have been reported in other trials, have also not been observed to date in this data cut and are comparable to placebo. We did see some mild taste changes, primarily following the first dose. There are other c-Kit-expressing tissues, including haematopoietic stem cells. In this regard, we observed very limited cases of neutrophil reductions, which were low grade and resolved within the study without any discontinuations or dose delays. Overall, these findings are very encouraging. It is very consistent with what we predicted based on our pharmacokinetic attributes, as well as what Tom described regarding the pharmacodynamic effects. The science is really lining up in terms of attributes of the molecule and how it is performing in the patient population.
Prof. Thomas Casale: I would like to just reinforce what we’ve been saying, in that c-Kit is present on a number of other cells besides mast cells, so you’re always concerned about any other potential adverse consequences.
I think the uniqueness of this drug lies in the fact that, unlike other c-Kit blockers explored in other clinical trails, briquilimab binds directly to the c-kit receptor and prevents stem cell factor from activating or binding to it. This provides a more targeted and effective way to block that activity, potentially offering a better therapeutic window by balancing the desired treatment effect with any potential adverse consequences.
Q. What have the initial findings revealed in terms of the efficacy of briquilimab?
Prof. Thomas Casale: To me, the efficacy was remarkable because it showed activity at almost every dose. The lower doses were not as clearly effective, but as the doses increased, the impact became more apparent.
There are a couple of unique aspects to these results. Number one, as I mentioned, in patients treated with either antihistamines or omalizumab, some patients experience a delayed response. We did not see that delay with briquilimab. Within one to two weeks, a significant number of patients experienced meaningful reductions in their urticaria scores, and that improvement was maintained throughout the dosing intervals. And once they were redosed, whether at 8 or 12 weeks, the reduction in symptoms was maintained.
I think that in itself is extremely encouraging, as it shows responsiveness in almost all patients and a rapid response to treatment. Additionally, well-controlled disease was achieved in over three-quarters of patients, typically at either 8 or 12 weeks.
Dr Ed Tucker: I’d just like to add to Tom’s comments here. Deep responses, as measured by the UAS7 (Weekly Urticaria Activity Score), are often the goal for clinicians like Tom, aiming to eliminate the symptoms. We observed this with complete responses in a significant number of patients at the higher doses.
This is highly encouraging for us. The rapid onset, the depth of response, and, as Tom mentioned, the durability of that response in sustaining reductions in UAS7 scores all indicate that we are effectively relieving patients of symptoms for prolonged periods. That is ultimately the goal when treating patients with CSU.
Q. How will these findings influence the next steps towards realizing the potential of briquilimab for treatment-refract CSU?
Dr Ed Tucker: From a trial perspective, we will continue to follow these patients in the existing cohorts, and then provide further information from those in subsequent scientific congresses.
We have also added patients to this study, including those in the single-dose cohorts of 240 milligrams and 360 milligrams. Additionally, we introduced two new cohorts: one testing a 240-milligram dose on a Q8-week regimen and another starting with 240 milligrams and stepping down to 180 milligrams on a Q8-week dosing schedule. All of this information will then provide us with greater insights into the pharmacokinetics and pharmacodynamics of this drug in this patient population, so that we can assess the doses that we can then take forward into registrational programs.
We will be initiating our registrational program in the second half of this year, which will include late-stage studies, such as a phase IIb leading into a phase III program, subject to discussions with regulatory agencies. So we’re very excited by this data.
Looking across the entire program, we also have our chronic inducible urticaria (CIndU) study [SPOTLIGHT], which will provide even more information to support this program. Additionally, we have the open-label extension, where patients from both the BEACON and SPOTLIGHT studies can continue on a 180-milligram dose administered on a Q8-week schedule. This extension will provide us with even more information on dosing, efficacy, and, of course, safety.
Prof. Thomas Casale: Adding to this, I would like to stress that the dosing regimen appears to allow for an extended dosing interval of eight weeks, and potentially even longer. This is a significant difference compared to treatments like anti-IL-4 (anti-interleukin-4) alpha blockers or oral BTK inhibitors, which require twice-daily oral dosing. Having the ability to not use the drug so frequently I think improves patient adherence.
The other point I would like to raise is that mast cells are not only a key cell in urticaria, they’re a key cell in a lot of disorders. So from my perspective, I think this opens up a number of different avenues that we could explore for other diseases that could really make an impact on millions of patients.
Dr Ed Tucker: The opportunities in mast cell-mediated diseases are very broad, and Jasper Therapeutics’ mission is to address several of these conditions. We began with CSU and CIndU, and have now expanded into the respiratory space as well. Additionally, we have initiated a proof-of-concept study in allergic asthma in Canada, and we look forward to sharing those results.
As Tom previously mentioned, this is exciting because we have not yet fully understood the interplay between mast cells and other inflammatory cells. By safely removing mast cells in various mast cell-mediated diseases, we can gain deeper understanding into both the underlying biology and the potential benefits of this drug for patients with these other diseases.
Prof. Thomas Casale: Additionally, it is the fact that this type of treatment is also agnostic to whatever you’re allergic to. So you could be allergic to house dust, mites, peanut, grass, whatever. If you take out the key effector cell, it really doesn’t matter what the trigger is, it should have a positive effect.
I’d like to finish by noting that we haven’t to date found a downside of getting rid of mast cells, except for putting me out of a job! But, otherwise, there hasn’t been any downside.
Dr Ed Tucker: Before we finish, I’d also like to take a moment to thank all the investigators, patients and their families who have contributed to our trials so far. We truly appreciate the dedication and efforts of our investigators across our programs. We will be looking for more investigators as we move into those registrational programs and will be expanding across a number of different territories in the future.
We look forward to connecting with many of these individuals at upcoming congresses. We will be attending AAAAI/WAO (American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress, 28 February to 3 March 2025, San Diego, CA, USA), AAD (American Academy of Dermatology Annual Meeting, 7-11 March 2025, Orlando, FL, USA) and later in the year, EAACI in Glasgow (European Academy of Allergy and Clinical Immunology Congress, 13-16 June 2025, Glasgow, UK). These are all opportunities for us to interact, understand and learn from key investigators such as Tom, who really help us with the program. We are extremely grateful for their contributions.
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Further content in urticaria.
Associated abstract: Casale T, Tucker E, Yuan J, et al. Initial results from BEACON, a phase 1b/2a dose escalation study of the anti-c-Kit briquilimab antibody in adults with chronic spontaneous urticaria (CSU). J Allergy Clin Immunol. 2025;155(Suppl.):Abstract L24.
Disclosures: Prof. Thomas Casale has served as a consultant for Sanofi, Genentech, Regeneron, Novartis, Jasper and Celldex. Additionally, he has participated in the Speaker’s Bureau for Sanofi, Regeneron and Genentech. Dr Ed Tucker is an employee of Jasper Therapeutics, a clinical stage biotechnology company focused on the development of briquilimab.
This content has been developed independently by Touch Medical Media for touchDERMATOLOGY and is not affiliated with the AAAAI or the WAO. Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Interviewer/Editor: Gina Furnival
Cite: BEACON study: Initial findings indicate briquilimab provides rapid and effective relief in chronic spontaneous urticaria. touchDERMATOLOGY, March 4 2025.
References
- Elieh-Ali-Komi D, Metz M, Kolkhir P, Kocatürk E, Scheffel J, Frischbutter S, Terhorst-Molawi D, Fox L, Maurer M. Chronic urticaria and the pathogenic role of mast cells. Allergol Int. 2023 Jul;72(3):359-368.
- Pooled Phase III Data Reinforce Dupilumab’s Efficacy in H1-Antihistamine Refractory CSU. touchDERMATOLOGY, March 3 2025
- gov. Dose Escalation Trial of Safety, Pharmacokinetic/Pharmacodynamic and Preliminary Clinical Activity of Briquilimab in Adult Patients with Chronic Spontaneous Urticaria (CSU) (BEACON). ClinicalTrials.gov identifier: NCT06162728. Available at: https://clinicaltrials.gov/study/NCT06162728 (accessed 28 February 2025).
- Casale T, Tucker E, Yuan J, et al. Initial results from BEACON, a phase 1b/2a dose escalation study of the anti-c-Kit briquilimab antibody in adults with chronic spontaneous urticaria (CSU). J Allergy Clin Immunol. 2025;155(Suppl.):AbstrAB435.
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