KalVista Pharmaceuticals, Inc. (NASDAQ: KALV) has announced the presentation of novel data on long-term prophylaxis (LTP) and sebetralstat at the Western Society of Allergy, Asthma & Immunology (WSAAI) 2025 Annual Meeting, held in Waimea, HI, from February 9-13, 2025.
Addressing Challenges in Hereditary Angioedema (HAE) Treatment
Hereditary angioedema (HAE) is a rare genetic disorder that causes recurrent episodes of severe swelling in various parts of the body, including the abdomen, face, airway, and extremities. While injectable on-demand treatments are available, they present side effects and logistical challenges that can impact disease management, often leading to an over-reliance on long-term prophylaxis.
Impact of Long-Term Prophylaxis Adherence
Dr. Raffi Tachdjian, MD, MPH, Associate Clinical Professor of Medicine and Pediatrics in the Division of Allergy and Clinical Immunology at the David Geffen School of Medicine at UCLA, presented findings from a claims database analysis examining LTP adherence among HAE patients.
According to a US commercial claims analysis, nearly 40% of HAE patients initiating LTP experienced significant refill gaps over 12 months. More than half of these individuals ultimately discontinued LTP. For patients with substantial refill gaps, on-demand treatment claims remained unchanged before and after one year of LTP initiation.
Despite guidelines recommending regular monitoring to ensure LTP efficacy and safety, the study indicates many patients face adherence challenges, potentially compromising the effectiveness of their treatment. “These data suggest a need for enhanced patient monitoring, as LTP does not always deliver the expected reduction in attack frequency,” Dr. Tachdjian noted. “Furthermore, our analysis may explain why on-demand treatment volumes have remained consistent despite the introduction of multiple effective subcutaneous and oral LTP options since 2017.”
Sebetralstat as an Emerging Oral On-Demand Therapy
Dr. Marc A. Riedl, MD, Professor of Medicine and Clinical Director at the US Hereditary Angioedema Association Center, University of California, San Diego, presented interim findings from the KONFIDENT-S open-label study evaluating the safety and effectiveness of sebetralstat in HAE patients receiving LTP.
Key findings from the study include:
- Patients receiving LTP treated 382 attacks with sebetralstat (averaging 1.7 attacks per month).
- More than half of these attacks involved the abdomen and/or larynx.
- Sebetralstat enabled early treatment (median 6 minutes) and symptom relief (median 1.3 hours).
- The treatment was well tolerated across different LTP mechanisms of action and routes of administration.
Dr. Riedl highlighted that treatment guidelines emphasize the need for rapid intervention in HAE attacks, regardless of LTP status. “These interim results suggest that, if approved, sebetralstat could be a reliable, safe, and effective oral on-demand option for breakthrough attacks, irrespective of their severity, location, or type of LTP used,” he said.
Sebetralstat in Patients Receiving Berotralstat
Dr. Michael E. Manning, MD, an allergist-immunologist at Allergy, Asthma and Immunology Associates in Scottsdale, Arizona, and past president of WSAAI, presented additional data from the KONFIDENT-S open-label study, specifically focusing on HAE patients receiving berotralstat for LTP.
Findings from this subset analysis include:
- Patients receiving berotralstat treated 178 attacks with sebetralstat (averaging 1.8 attacks per month).
- Sebetralstat facilitated early treatment (median 20 minutes) and symptom relief (median 1.3 hours).
- No increase in gastrointestinal side effects was observed.
Dr. Manning emphasized the strong preference among patients for oral treatments over injectables, stating, “These results highlight sebetralstat’s potential as a transformative oral on-demand therapy for HAE, particularly for patients already using berotralstat for LTP. If approved, sebetralstat could provide an effective needle-free alternative.”
A New Paradigm in HAE Management
Paul Audhya, MD, MBA, Chief Medical Officer of KalVista, underscored the limitations of current injectable on-demand therapies, noting that they present barriers to effective disease control and contribute to the overuse of LTP.
“LTP does not always yield the anticipated reductions in attack frequency, likely due to adherence challenges in a lifelong chronic condition,” Dr. Audhya said. “Sebetralstat has demonstrated the potential to allow early treatment of attacks, preventing progression and reducing morbidity. By addressing limitations of existing injectable therapies, sebetralstat could redefine HAE management.”
The KONFIDENT Phase 3 Trial
The KONFIDENT Phase 3 clinical trial was a randomized, double-blind, three-way crossover study assessing the safety and efficacy of sebetralstat at 300 mg and 600 mg doses versus placebo. It enrolled 136 patients across 66 clinical sites in 20 countries, making it the largest HAE trial conducted to date.
Participants treated up to three attacks with the study drug, and the trial included both Type I and Type II HAE patients with a history of at least two attacks within 90 days prior to randomization. The study also included individuals receiving LTP.
The KONFIDENT-S Open-Label Extension Trial
The KONFIDENT-S trial is an ongoing open-label extension study incorporating real-world elements to evaluate the long-term safety and efficacy of sebetralstat in adults and adolescents (aged 12 and older) with Type I or Type II HAE. KalVista is transitioning participants to a novel oral disintegrating tablet (ODT) formulation, with a planned 2026 supplemental new drug application (sNDA) filing. If approved, the ODT formulation would offer patients an innovative, convenient oral on-demand treatment option.
About Sebetralstat
Sebetralstat is an investigational, oral plasma kallikrein inhibitor developed for the treatment of hereditary angioedema. KalVista has submitted multiple regulatory applications seeking approval of sebetralstat as the first oral on-demand treatment for HAE in individuals aged 12 and older, with further studies exploring its use in children aged 2 to 11. If approved, sebetralstat could become a foundational therapy for HAE management worldwide.
About Hereditary Angioedema
Hereditary angioedema is a rare genetic condition characterized by a deficiency or dysfunction of the C1 esterase inhibitor (C1INH) protein, leading to unregulated activation of the kallikrein-kinin system. This results in painful and potentially life-threatening swelling attacks. Currently, all approved on-demand treatments require either intravenous or subcutaneous administration.
About KalVista Pharmaceuticals, Inc.
KalVista Pharmaceuticals, Inc. is a global biopharmaceutical company focused on developing and delivering transformative oral therapies for individuals affected by rare diseases with significant unmet needs. The company’s lead investigational product, sebetralstat, is under regulatory review by the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) goal date of June 17, 2025. KalVista has also completed Marketing Authorization Applications for sebetralstat with the European Medicines Agency and multiple other regulatory bodies worldwide.
For further information, including links to all presentations from the WSAAI 2025 Annual Meeting, visit the KalVista website under Publications.
