FDA will not meet original PDUFA data for sebetralstat to treat HAE | Image Credit: Contemporary Pediatrics

The FDA will not meet a prescription drug user fee act (PDUFA) date of June 17, 2025, for a decision regarding the potential approval of sebetralstat (KalVista Pharmaceuticals) to treat hereditary angioedema (HAE) in patients aged 12 years and older. According to a press release from KalVista, the delay is because of "heavy workload and limited resources," at the FDA. Despite the delay, the agency informed KalVista it expects to deliver a decision within approximately 4 weeks.^1,2

The federal agency did not request additional data or studies and has not raised any concern about the safety, efficacy, or approvability of sebetralstat. All prior information requests were addressed by KalVista, which stated it believes "the only remaining item under FDA review is the finalization of the labelling."¹

“We are disappointed by this delay, most importantly because we know how much people living with HAE are looking forward to an oral on-demand option to treat their HAE attacks,” said Ben Palleiko, CEO of KalVista in a statement. "At the same time, we remain confident in the near-term approval of sebetralstat. We are continuing to work closely with the FDA to support the completion of their review. Our commitment to bringing this important therapy to people living with HAE remains unwavering.”

Details, data on sebetralstat for HAE

A new drug application (NDA) for sebetralstat was accepted by the FDA on September 3, 2024, to treat HAE attacks in adult and pediatric patients aged 12 years and older. The NDA for the novel, investigational, oral plasma inhibitor for on-demand treatment of HAE was submitted based on data from the phase 3 KONFIDENT clinical trial, as well as the KONFIDENT-S open-label extension trial.³

Sebetralstat met the primary endpoint for the phase 3 trial, with both 300 mg and 600 mg formulations having achieved the beginning of symptom relief significantly faster than placebo (P < 0.0001 for 300 mg; P = 0.0013 for 600 mg). Additionally, the investigational treatment was well-tolerated, with a safety profile similar to placebo. In the open-label extension, sebetralstat enabled patients to treat attacks with a median time from attack onset to treatment of 9 minutes. Results also demonstrated a median time to beginning of symptom relief for laryngeal attacks of 1.3 hours.

Shortly after the FDA accepted the NDA for sebetralstat, KalVista announced the presentation of data at the Bradykinin Symposium 2024, which took place in Berlin, Germany.⁴

At the time of the symposium, and regarding the data presented—Emel Aygören-Pürsün, MD, specialist in internal medicine at the Division of Oncology, Hematology and Hemostaseology at the Department for Children and Adolescents of the University Hospital Frankfurt, and a leading investigator for the phase 2, phase 3 KONFIDENT and KONFIDENT-S trials—stated the following:

"Delay or denial in the treatment of HAE attacks is often related to the administration of the currently approved injectable on-demand treatments which commonly result in injection-site reactions or pain. The data presented... highlight that oral sebetralstat may remove these challenges and has a safety profile no different than placebo. Sebetralstat also resulted in rapid symptom relief in the clinical trials. If approved, sebetralstat might become a major advance for people living with HAE by addressing critical gaps in the current standard of care for on-demand treatment of attacks."

References:

1. KalVista Pharmaceuticals announces FDA will not meet PDUFA goal date for sebetralstat NDA for hereditary angioedema due to FDA resource constraints. KalVista Pharmaceuticals. June 13, 2025. Accessed June 16, 2025. https://www.businesswire.com/news/home/20250613608281/en/KalVista-Pharmaceuticals-Announces-FDA-Will-Not-Meet-PDUFA-Goal-Date-for-Sebetralstat-NDA-for-Hereditary-Angioedema-Due-to-FDA-Resource-Constraints

2. Ebert M. 5 pediatric FDA decisions to watch for in Q2 2025. Contemporary Pediatrics. March 28, 2025. Accessed June 16, 2025. https://www.contemporarypediatrics.com/view/5-pediatric-fda-decisions-to-watch-for-in-q2-2025

3. KalVista announces FDA acceptance of new drug application for sebetralstat for oral on-demand treatment of hereditary angioedema. September 3, 2024. Accessed June 16, 2025. https://www.businesswire.com/news/home/20240903673442/en/KalVista-Announces-FDA-Acceptance-of-New-Drug-Application-for-Sebetralstat-for-Oral-On-Demand-Treatment-of-Hereditary-Angioedema

4. KalVista Pharmaceuticals presents sebetralstat data at Bradykinin Symposium 2024. Accessed June 16, 2025. https://www.businesswire.com/news/home/20240906021663/en/KalVista-Pharmaceuticals-Presents-Sebetralstat-Data-at-Bradykinin-Symposium-2024