On-demand sebetralstat quickly eases attacks in long-term HAE trial

Patients experience symptom relief within 2 hours, resolution within 1 day

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Most hereditary angioedema (HAE) patients are able to take on-demand oral tablets of sebetralstat within 10 minutes of a swelling attack starting, and begin experiencing symptom relief within two hours, with complete resolution within about a day.

That’s according to interim findings from an open-label extension Phase 3 clinical trial, called KONFIDENT-S trial (NCT05505916), that could include HAE patients who completed the placebo-controlled Phase 3 KONFIDENT trial (NCT05259917).

“Compared to KONFIDENT, … KONFIDENT-S has many real-world elements which enabled patients to treat attacks even earlier as evidenced by a median time to treatment of 9 minutes,” Henriette Farkas, MD, PhD, a study investigator at Semmelweis University in Budapest, Hungary, said in a press release from sebetralstat’s developer KalVista Pharmaceuticals.

“These results further validate the promise of an oral on-demand treatment. By acting quickly, patients may halt the progression of attacks before they become severe and thereby minimize the burden of their attacks and the time to improvement and resolution of their symptoms,” Farkas added.

Farkas presented the findings at the recent European Academy of Allergy and Clinical Immunology Congress 2024, held in Valencia, Spain, in a poster, titled “Sebetralstat as Oral On-demand Treatment for Hereditary Angioedema: Interim Analysis of Demographics and Attack Characteristics from the Open-label KONFIDENT-S Trial.”

At the same conference, KalVista shared full results from the KONFIDENT study in an oral presentation, titled “Oral Sebetralstat for On-Demand Treatment of Hereditary Angioedema: Phase 3 KONFIDENT Trial Results.” The findings were also published in The New England Journal of Medicine.

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Results could help support future applications for sebetralstat in US, EU, Japan

“The efficacy and safety data … support the potential of sebetralstat as the first new treatment approach for the on-demand treatment of HAE in more than a decade, and the first potential oral therapy for this indication,” said Paul Audhya, MD, KalVista’s chief medical officer.

KalVista is planning to use the results as a basis to apply for sebetralstat’s approvals.

“We look forward to submitting a new drug application for sebetralstat to the US [Food and Drug Administration] in June 2024 and in the [European Union] and Japan later this year,” said Ben Palleiko, KalVista’s CEO.

KONFIDENT enrolled more than 100 people, 12 years and older, with HAE types 1 or 2. When experiencing a swelling attack, patients received on-demand treatment with either one of two doses of sebetralstat (300 or 600 mg) or a placebo.

Results showed patients treated swelling attacks after a median of 41 minutes, with 55.7% of participants treating in less than one hour.

Either dose of sebetralstatat was associated with a significantly faster time to the start of symptom relief (within two hours vs. more than six hours), and faster reduction in attack severity (within nine hours vs. more than 12 hours).

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40%-50% given sebetralstat had complete resolution of attacks within a day

About 40%-50% of patients given sebetralstat had complete resolution of attacks within a day, compared with 27.4% of those given a placebo. Safety findings were between sebetralstat and placebo groups.

“For many years, HAE patients and their caregivers have sought an oral on-demand treatment option that would allow them to effectively and safely manage their attacks and take control of their disease,” said Danny Cohn, MD, PhD, principal investigator for the KONFIDENT study at Amsterdam University Medical Centre. “The KONFIDENT results demonstrate that sebetralstat has the potential to meet that need.”

Analyses showed the therapy’s efficacy was consistent regardless of attack severity, where on the body swelling was occurring, and whether or not patients were taking long-term preventive therapy.

“These data reinforce that, if approved, sebetralstat would have the potential to transform the treatment landscape,” Cohn said.

After completing KONFIDENT, participants could opt to enroll in the long-term KONFIDENT-S study, where all participants are getting on-demand treatment with sebetralstat for swelling attacks. KONFIDENT-S is also actively enrolling new HAE patients at locations worldwide.

Newly presented data were collected through early February, at which point 112 patients had enrolled. A total of 649 swelling attacks had been treated, with most patients receiving on-demand sebetralstat for five or more attacks.

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Patients took sebetralstat about 9 minutes after attack onset

Results showed patients took sebetralstat at a median of nine minutes after attack onset — considerably faster than the median 41 minutes in KONFIDENT.

The median time to when patients started feeling symptom relief was 1 hour and 48 minutes, time to attack severity reduction was about 6.5 hours, and time to complete resolution was about 21 hours, consistent with KONFIDENT results.

Faster timings were reported for the 14 evaluable laryngeal, or throat, attacks, which can be deadly if swelling blocks the windpipe. Specifically, it took a median of 1 hour and 18 minutes for patients to start feeling some symptom relief, 1.5 hours for them to experience a reduction in attack severity, and nearly seven hours to achieve complete resolution.

“We want to thank the trial participants, their families, their advocates, and the investigator teams around the world who supported KONFIDENT and continue to support KONFIDENT-S,” Palleiko said.