– 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 –
KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), today announced
that late-breaking data from the pivotal phase 3 KONFIDENT trial
and open label KONFIDENT-S extension trial evaluating the efficacy
and safety of sebetralstat were presented as late-breaking
presentations at the European Academy of Allergy and Clinical
Immunology Congress 2024. The results of KONFIDENT were
simultaneously published in The New England Journal of
Medicine.
“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
- 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 2.3% for 300
mg sebetralstat, 3.2% for 600 mg sebetralstat, and 4.8% for
placebo.
“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)
- 112 participants enrolled (Europe 50.0%, US 27.7%, other 22.3%)
- 15.2% aged 12-<18 years, 81.3% aged 18-<65 years, and
2.7% aged ≥65 years
- 68.8% receiving on-demand treatment only; 31.3% receiving
stable long-term prophylaxis
- 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, Budapest, Hungary. “Importantly, we also
learned that sebetralstat’s effect in laryngeal attacks was
consistent with the results in all other attack locations.”
“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 Japan
later this year,” said Ben Palleiko, Chief Executive Officer of
KalVista.
The publication for NEJM can be found at the below link:
http://www.nejm.org/doi/full/10.1056/NEJMoa2314192?utm_source=conf&utm_medium=qr&utm_campaign=EAACI2024
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 U.S. FDA, as well as Orphan
Drug Designation and an approved Pediatric Investigational Plan
from the European Medicines Agency (EMA).
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 U.S. Food and
Drug Administration (FDA) for sebetralstat in June 2024 and expects
to file for approval in the UK, Europe, and Japan later in
2024.
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 U.S. Private
Securities Litigation Reform Act of 1995. Forward-looking
statements can be identified by words such as: "anticipate,"
"intend," "plan," "goal," "seek," "believe," "project," "estimate,"
"expect," "strategy," "future," "likely," "may," "should," "will"
and similar references to future periods. These statements are
subject to numerous risks and uncertainties that could cause actual
results to differ materially from what we expect. Examples of
forward-looking statements include, among others, timing or
outcomes of communications with the FDA or other international
regulatory agencies, our expectations about safety and efficacy of
our product candidates, our ability to obtain regulatory approvals
for sebetralstat and other candidates in development within our
expected timelines or at all, our success in engaging with
potential commercial partners, the success of any efforts to
commercialize sebetralstat, the ability of sebetralstat and other
candidates in development to treat HAE or other diseases, our
ability to commence pediatric trials of sebetralstat and develop an
ODT formulation, the future progress and potential success of our
oral Factor XIIa program, our ability to reduce spending on
discovery and preclinical activities, and our expectation to become
cash flow positive. Further information on potential risk factors
that could affect our business and financial results are detailed
in our filings with the Securities and Exchange Commission,
including in our annual report on Form 10-K for the year ended
April 30, 2023, our quarterly reports on Form 10-Q, and our other
reports that we may make from time to time with the Securities and
Exchange Commission. We undertake no obligation to publicly update
any forward-looking statement, whether written or oral, that may be
made from time to time, whether as a result of new information,
future developments or otherwise.
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version on businesswire.com: https://www.businesswire.com/news/home/20240531104408/en/
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
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