KalVista Pharmaceuticals Announces New England Journal of Medicine Publishes Oral Sebetralstat Phase 3 Data Demonstrating its Potential to Transform the Treatment Landscape for People with Hereditary Angioedema
KalVista Pharmaceuticals announced that data from the phase 3 KONFIDENT trial of sebetralstat, an oral treatment for hereditary angioedema (HAE), was published in the New England Journal of Medicine and presented at the European Academy of Allergy and Clinical Immunology Congress 2024.
The trial met its primary and secondary endpoints, with a median symptom relief time of 1.61 hours for 300 mg and 1.79 hours for 600 mg doses, compared to 6.72 hours for placebo. The safety profile was comparable to placebo, with low adverse event rates.
In the KONFIDENT-S open-label trial, sebetralstat showed a median treatment time of 9 minutes and a median symptom relief time of 1.8 hours, with consistent efficacy across various attack severities and locations.
KalVista plans to submit a new drug application to the US FDA in June 2024, and later in the EU and Japan.
- Phase 3 KONFIDENT trial met primary and secondary endpoints.
- Median time to symptom relief: 1.61 hours (300 mg) and 1.79 hours (600 mg) vs. 6.72 hours for placebo.
- Safety profile comparable to placebo with low adverse event rates.
- KONFIDENT-S trial showed a median treatment time of 9 minutes and a median symptom relief time of 1.8 hours.
- Consistent efficacy regardless of attack severity, location, or prophylaxis use.
- No patient withdrawals or treatment-related serious adverse events.
- KalVista plans a new drug application to the US FDA in June 2024.
- Planned submissions to the EU and Japan later in 2024.
- Adverse event rates, while low, were slightly higher with sebetralstat (2.3% for 300 mg, 3.2% for 600 mg) compared to placebo (4.8%).
- Long median time to complete attack resolution (21 hours) in KONFIDENT-S trial.
- Uncertainty remains until FDA and other regulatory approvals are obtained.
Insights
KalVista Pharmaceuticals' Phase 3 KONFIDENT trial results are noteworthy for multiple reasons. First, the study met its primary and key secondary endpoints, which is a positive indicator of the drug's potential efficacy. This positions sebetralstat as a strong candidate for approval by regulatory bodies such as the FDA. Investors should note the statistical significance of the trial results (e.g.,
The strong safety profile of sebetralstat, showing no significant difference from placebo, further enhances its approval prospects. No patient withdrawals and low treatment-related adverse event rates (2.3% for 300 mg, 3.2% for 600 mg) support this point.
KalVista's intention to submit a new drug application for sebetralstat to the FDA in June 2024 indicates a clear path forward. If approved, this could result in significant revenue streams, enhancing future earnings and potentially increasing shareholder value.
In the short term, investors might see some stock price volatility as the market digests this news, but the long-term outlook appears promising given the potential market size for an effective HAE treatment.
The results from the KONFIDENT trial are significant for the HAE treatment landscape. Notably, the trial demonstrated that sebetralstat can provide rapid symptom relief with a median time to beginning of symptom relief of 1.61 hours (300 mg) and 1.79 hours (600 mg), compared to 6.72 hours for placebo. This speed of action is important for HAE patients who require swift intervention to manage acute attacks.
Additionally, the consistent efficacy across various attack severities and locations indicates a robust drug performance, which is critical for patient confidence and adherence to the treatment.
The interim results of the KONFIDENT-S open-label extension trial, with a median time from attack onset to treatment of 9 minutes, highlight the potential 'real-world' effectiveness of sebetralstat, which is an encouraging sign for its practical usability. This rapid treatment ability could dramatically improve patient outcomes and quality of life.
The publication of the KONFIDENT trial results in the New England Journal of Medicine and presentations at a major European medical congress provide strong external validation of the research. This can enhance the drug's credibility within the medical community and among potential partners or acquirers.
Moreover, achieving these milestones in highly visible and respected platforms can positively impact brand reputation and investor confidence. Given the unmet need for effective, oral on-demand treatments for HAE, sebetralstat's market introduction could capture significant market share, especially considering its ability to provide swift symptom relief and its favorable safety profile.
In the longer term, successful market penetration and potential expansion into other geographical markets (EU and Japan as mentioned) could provide substantial revenue growth and market positioning opportunities for KalVista.
– Late-breaking data from phase 3 KONFIDENT trial of sebetralstat published in NEJM and presented concurrently at the European Academy of Allergy and Clinical Immunology Congress 2024 –
– Interim data from KONFIDENT-S open-label trial show median time to treatment of 9 minutes and median time to beginning of symptom relief for laryngeal attacks 1.3 hours –
“The phase 3 KONFIDENT results represent a major advance for people living with HAE and reinforce our commitment to addressing critical gaps in the current standard of care,” said Paul Audhya, MD, MBA, KalVista’s Chief Medical Officer. “The efficacy and safety data presented as a late-breaker at EAACI and simultaneously published in The New England Journal of Medicine 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.”
As presented and published, the KONFIDENT trial met its primary and key secondary endpoints and demonstrated a safety profile no different from placebo.
Phase 3 KONFIDENT Trial Results
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Median time from attack onset to treatment was 41 min (Q1, 6; Q3, 140) with
55.7% of participants treating in less than 1 hour -
42.8% of attacks treated when still mild
Primary endpoint:
- Time to beginning of symptom relief was significantly faster than placebo (p<0.0001 for 300 mg sebetralstat, p=0.0013 for 600 mg sebetralstat)
- Median time to beginning of symptom relief was 1.61 hours with sebetralstat 300 mg (IQR, 0.78-7.04), 1.79 hours with sebetralstat 600 mg (IQR, 1.02-3.79), and 6.72 hours with placebo (IQR, 1.34->12)
Key secondary endpoints:
- Significantly faster time to a reduction in attack severity from baseline compared to placebo (p=0.0036 for 300 mg sebetralstat, p=0.0032 for 600 mg sebetralstat)
- Significantly faster time to complete attack resolution compared to placebo (p=0.0022 for 300 mg sebetralstat, p<0.0001 for 600 mg sebetralstat)
Primary and key secondary endpoints were analyzed in a fixed, hierarchical sequence and adjusted for multiplicity. Subgroup analyses showed a consistency of treatment effect in among attacks regardless of attack severity, attack location, use of long-term prophylaxis, or geography.
The safety of sebetralstat at both dose levels was no different than placebo. There were no patient withdrawals due to any adverse events and no treatment-related serious adverse events (SAEs) were observed. Treatment-related adverse event rates were
“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. The KONFIDENT results demonstrate that sebetralstat has the potential to meet that need,” said Danny Cohn, MD, PhD, Department of Vascular Medicine, Amsterdam University Medical Centre, and principal investigator for the KONFIDENT phase 3 trial. “Sebetralstat provided rapid symptom relief with a safety profile no different from placebo. It was also encouraging to see that efficacy was consistent regardless of attack severity, anatomic location or the use of long-term prophylaxis. These data reinforce that, if approved, sebetralstat would have the potential to transform the treatment landscape.”
Phase 3 KONFIDENT-S Open-Label Extension Trial Interim Results (as of February 2, 2024)
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112 participants enrolled (
Europe 50.0% , US27.7% , other22.3% )-
15.2% aged 12-<18 years,81.3% aged 18-<65 years, and2.7% aged ≥65 years -
68.8% receiving on-demand treatment only;31.3% receiving stable long-term prophylaxis
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- 649 attacks treated with sebetralstat; median 5.0 attacks treated per participant (range, 1-39)
- Median time from attack onset to treatment was 9 minutes (IQR 1-69)
- Median time to beginning of symptom relief was 1.8 hours
- Median times to reduction in attack severity (6.57 hours [IQR 1.61->12]) and complete attack resolution (21.0 hours [IQR 7.22->24]) were consistent with results in the KONFIDENT Trial. KONFIDENT and KONFIDENT-S are the first and only clinical trials ever to include complete symptom relief as an endpoint; all other trials use near-complete relief, which is a much lower standard that does not capture the entire attack sequence in the same manner.
- Laryngeal attack subgroup (n=14), median time to beginning of symptom relief was 1.3 hours
“Compared to KONFIDENT, which is a placebo-controlled crossover trial, 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. 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,” said Henriette Farkas, MD, PhD, Hungarian Angioedema Center of Reference and Excellence, Department of Internal Medicine and Haematology, Semmelweis University,
“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. As reported at EAACI, as of May 7, 2024, KONFIDENT-S participants have treated over 1000 attacks with sebetralstat (including 24 laryngeal attacks). We look forward to submitting a new drug application for sebetralstat to the US FDA in June 2024 and in the EU and
The publication abstract can be found at the below link:
https://www.nejm.org/doi/full/10.1056/NEJMoa2314192
Links to all posters and presentations can be found on the KalVista website under “Publications”.
About the KONFIDENT Phase 3 Trial
The KONFIDENT phase 3 trial was a randomized, double blind, event-driven, crossover clinical trial evaluating the efficacy and safety of sebetralstat 300 mg and 600 mg versus placebo for the on-demand treatment of HAE. The trial enrolled a total of 136 adult and adolescent HAE patients from 66 clinical sites across 20 countries, making it the largest clinical trial ever conducted in HAE. In the trial, patients treated each eligible attack with up to two doses of study drug, and each patient could treat up to three attacks over the course of the study. The trial included type 1 and type 2 HAE patients who had at least two attacks in 90 days prior to enrollment.
About the KONFIDENT-S Trial
The KONFIDENT-S trial is an open label extension study evaluating the long-term safety of sebetralstat for on-demand treatment of HAE attacks in adolescents (aged 12-17) and adult patients with HAE Type I or Type II. The trial is also evaluating sebetralstat for use as a short-term prophylaxis treatment prior to medical procedures.
About Sebetralstat
Discovered by KalVista, sebetralstat is an investigational novel, oral plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema (HAE). Sebetralstat received Fast Track and Orphan Drug designations from the
About Hereditary Angioedema
Hereditary angioedema (HAE) is a rare genetic disease resulting in deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein and subsequent uncontrolled activation of the kallikrein-kinin system. People living with HAE experience painful and debilitating attacks of tissue swelling in various locations of the body that can be life-threatening depending on the location affected. All currently approved on-demand treatment options require either intravenous or subcutaneous administration.
About KalVista Pharmaceuticals, Inc.
KalVista Pharmaceuticals, Inc. is a global pharmaceutical company focused on the development and delivery of oral medicines for diseases with significant unmet need. KalVista disclosed positive phase 3 data for the KONFIDENT trial for its oral, on-demand therapy sebetralstat in February 2024. The Company anticipates submitting a new drug application to the
For more information about KalVista, please visit www.kalvista.com.
Forward-Looking Statements
This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the
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KalVista Pharmaceuticals, Inc.
Jarrod Aldom
Vice President, Corporate Communications
(201) 705-0254
jarrod.aldom@kalvista.com
Ryan Baker
Head, Investor Relations
(617) 771-5001
ryan.baker@kalvista.com
Source: KalVista Pharmaceuticals, Inc.
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