New sebetralstat data presented at the 2024 American College of Allergy Asthma and Immunology-KalVista Pharmaceuticals

Tim Craig, DO, Professor, Departments of Medicine and Pediatrics, Division of Pulmonary, Allergy and Critical Care Medicine, Penn State Health, and KONFIDENT investigator, presented data on the Correlation of Time to Treatment with Attack Duration in the Sebetralstat KONFIDENT Phase III Trial that showed complete attack resolution was achieved faster in attacks that were treated earlier (1^st quartile) compared with those treated later (4^th quartile). “This is the first time in a Phase III on-demand trial where we can see that treating attacks within minutes versus hours has a meaningful impact on clinical outcomes. While injectable on-demand therapies are effective, there are numerous barriers patients face that lead to delay or denial of HAE on-demand treatment,” said Dr. Craig. “These data help to clarify the potential value of sebetralstat if approved: reduced burden enabling patients to treat attacks early and achieve earlier symptom relief and shorter attack duration.”

William Lumry, MD, Medical Director AARA Research Center, Dallas and KONFIDENT investigator, presented data on the Substantial Reduction of HAE Symptom Burden in the Sebetralstat Phase III KONFIDENT Trial which showed that among attacks that had progressed to at least moderate severity on the Patient Global Impression of Severity (PGI-S) prior to treatment, those treated with sebetralstat 300mg (n=49, P=0.002) and sebetralstat 600mg (n=52, P=0.034) achieved a faster reduction in substantial symptom burden (reduction in PGI-S to “mild”) than with placebo (n=46), with median times of 5.0 hours, 5.2 hours, and >12 hours, respectively.

“All other clinical trial designs for on-demand therapy have required attacks to be at least moderate in severity to be eligible to treat. This changed with the sebetralstat Phase 2 and 3 trials which, consistent with modern HAE guidelines, instructed patients to treat attacks early. Despite this, approximately half of attacks progressed in severity prior to treatment,” said Dr. Lumry. “Among these more severe attacks, which were treated somewhat later, sebetralstat reduced symptom burden to “mild” significantly faster than placebo, with a median time of approximately 5 hours for sebetralstat vs >12 hours for placebo.”

The following are details for the additional ePoster - Meet the Author data presentations at ACAAI 2024:

• Indirect Treatment Comparison of Oral Sebetralstat and Intravenous rhC1-INH as On demand Treatments for Hereditary Angioedema: H. Henry Li, Institute for Asthma and Allergy, Chevy Chase, MD, USA
  • The network meta-analysis (NMA) fixed effects model found no significant differences in time to beginning of symptom relief between sebetralstat 300mg and IV-rhC1-INH 50 IU/kg (HR [95% CI] 0.96 [0.42-2.15] to 1.19 [0.58-2.45]).
  • After adjusting for baseline attack severity, matching-adjusted indirect comparison showed numerically favorable results with sebetralstat versus IV-rhC1-INH.
• On-demand Treatment of Laryngeal Hereditary Angioedema Attacks with Sebetralstat: Pooled Analysis from KONFIDENT and KONFIDENT-S: Emel Aygören-Pürsün, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
  • Pooled Analysis from KONFIDENT and KONFIDENT-S included 16 laryngeal attacks treated with sebetralstat 600mg. Median time to treatment was 8 minutes.
  • Median time to beginning of symptom relief was 1.5 hours; median time to reduction in severity was 1.7 hours; median time to complete attack resolution was 9.7 hours.
• Patient-Reported Anxiety Impacts Utilization of Injectable On-demand Treatment of Hereditary Angioedema Attacks: Cristine Radojicic, Duke University School of Medicine, Durham, NC, USA
  • The survey highlighted patients with Type I/II HAE who reported waiting 2.4 hours to treat their HAE attack after recognizing the initial onset of the attack.
  • Those who were experiencing anxiety related to their injectable on-demand treatment were most likely to delay or not treat attacks.

“The HAE community has long sought a less invasive treatment option that combines needed efficacy with lower treatment burden. These presentations continue to demonstrate that sebetralstat has the potential to provide injectable-like efficacy in a pill,” said Ben Palleiko, CEO of KalVista Pharmaceuticals. “If approved, sebetralstat will be the only on-demand treatment option that will have demonstrated the ability to enable compliance with treatment guidelines that call for early treatment of attacks, regardless of severity or location.”