The Lancet, the international weekly medical journal, publishes results from the phase 2 trial evaluating the efficacy and safety of KalVista Pharmaceuticals, Inc.‘s oral sebetralstat for the on-demand treatment of HAE.

The phase 2 study was a two-part, randomized, double-blind, placebo-controlled clinical trial. The trial included a total of 68 patients with HAE and showed that oral sebetralstat was well tolerated and led to rapid suppression of plasma kallikrein activity, resulting in significantly increased time to use of conventional treatment, reduced attack severity, and faster time to symptom relief and resolution compared to placebo.

“All currently available on-demand treatments in HAE require injections and are associated with substantial treatment burden and delays due to the time required for medication preparation and administration, and associated pain and discomfort,” says Dr. Emel Aygören-Pürsün, Head of the HAE Center at the University Hospital Frankfurt, Germany, co-lead author of the manuscript, and Principal Investigator for the phase 2 clinical trial. “In this study, patients were able to orally administer treatment early after attack onset, minimizing time to improvement. This suggests that sebetralstat has the potential to enable patients to improve clinical outcomes.”

“Sebetralstat was rapidly absorbed after oral administration, halting attack progression and expediting symptom relief and attack resolution,” adds Dr. Andrea Zanichelli, Unità di Medicina, IRCCS Policlinico San Donato, Università degli Studi di Milano, Italy, and co-lead author. “Importantly, sebetralstat was well-tolerated in this trial with very few adverse events. The preliminary safety profile contrasts favorably with the labelled adverse reactions for currently approved on-demand therapies.”

“The publication of these phase 2 results in The Lancet underscores their significance and represents further validation of the promise of sebetralstat as potentially the first oral on-demand treatment for people living with HAE,” says Andrew Crockett, CEO of KalVista. “We anticipate clinical results from our ongoing phase 3 KONFIDENT trial for sebetralstat for on-demand treatment in HAE in the second half of this year as we work to bring this innovative therapy to the HAE community.”

Topline Phase 2 Sebetralstat Results

  • Time to use of conventional treatment within 12 h of study drug administration was significantly longer with sebetralstat versus placebo; (p=0·0010)
  • Sebetralstat significantly reduced time to onset of symptom relief (p=<0.0001) on the Patient Global Impression of Change scale (PGI-C), with a median time of 1.6 hours versus 9 hours for attacks treated with placebo
  • Time to conventional attack treatment use or worsening in severity by 1 level or more on the PGI-S, whichever came first, within 12 h of study administration was significantly longer after treatment with sebetralstat than after treatment with placebo (p<0.001)
  • The median time to attack resolution, defined as a PGI-S rating of “none” within 24 h after study drug administration, was significantly shorter with sebetralstat than with placebo (p=0·0021)
  • Sebetralstat was well-tolerated and no serious adverse events were reported. The proportion of drug-related treatment-emergent adverse events was similar in attacks treated with sebetralstat and placebo

(Source: KalVista)