KONFIDENT was a multinational, randomized, double-blind,
placebo-controlled, phase 3, crossover study of 136
patients from 17 countries. Study participants were
randomized to receive either placebo, EKTERLY 300 mg, or
EKTERLY 600 mg to treat 3 attacks in
a 3-way crossover
design using 1 of 6 treatment sequences.2,3
Efficacy
and Safety
Real EKTERLY patient
Rapid time to beginning of symptom relief with EKTERLY1,2
KONFIDENT EFFICACY
Primary Endpoint (PGI-C): median time to the beginning of symptom relief1,2
-
Ekterly
1.8
hours
-
-
Placebo
6.7
hours
Based on prespecifying that attacks with incomplete data were censored at timepoint zero. Analysis included in label assigns these attacks a value of 12 hours, resulting in a median of 2.0 hours.1,2
Explore the primary endpoint
Time to symptom relief was
consistent
across
attack locations, severities, and patient
demographics2
One-dose symptom relief
96% of attacks
that
reached the primary
endpoint achieved
symptom relief
with only 1 dose3
KONFIDENT study
design
Time to end of progression with EKTERLY was evaluated in a post hoc analysis4,5
KONFIDENT POST HOC ANALYSIS
Design criteria
Time to end of progression was defined as the time at
which the worst attack severity was recorded using the
5-point PGI-S scale (none to severe) within
12
hours.1,4
- PGI-S was assessed every 30 minutes (with early entries permitted) for the first 4 hours, then hourly for hours 5 to 12 after administration2
- Conventional medication use within 12 hours was
censored at the time of use. Attacks with no
postbaseline assessment and no conventional
medication use were excluded. If the worst symptom
was achieved after
12 hours, then end of progression analysis was censored at 12 hours4
Median time to end of progression
(n=88
attacks)4
-
-
Ekterly
19.8
minutes
LIMITATIONS
This was a post hoc analysis, and, therefore, the results should be interpreted with caution. The analysis was conducted retrospectively and cannot be used to demonstrate statistically significant differences between treatment groups.
KONFIDENT SAFETY
Safety events with EKTERLY were similar to placebo1
Adverse Events Observed in ≥2% of Patients and More Common Than Placebo1
| Adverse Events | EKTERLY (n=93) | PLACEBO (n=83) |
|---|---|---|
| Headache | 3 (3.2%) |
1 (1.2%) |
• 0 discontinuations due to adverse events2
HAE=hereditary angioedema; PGI-C=Patient Global Impression of Change scale; PGI-S=Patient Global Impression of Severity; TEAE=treatment-emergent adverse event.
KONFIDENT-S 2-YEAR,
OPEN-LABEL
EXTENSION6
Safety events in the KONFIDENT-S trial were consistent with those in KONFIDENT1,6
Adverse Events Observed in ≥2% of the Overall Population in KONFIDENT-S7
| Treatment-Related TEAEs | |
|---|---|
| Any treatment-related TEAE | 12 (9.0%) |
| Headache | 5 (3.7%) |
| Vomiting | 3 (2.2%) |
1700+ attacks of all severities
and in
all locations were
treated with
EKTERLY7-9,*
| Primary attack locations | EKTERLY-treated attacks |
|---|---|
| Abdomen | 645 (37.8%) |
| Arms/hands | 490 (28.7%) |
| Legs/feet | 403 (23.6%) |
| Head/face/neck | 129 (7.6%) |
| Torso | 99 (5.8%) |
| Genitals | 84 (4.9%) |
| Larynx/throat† | 32 (1.9%) |
| Baseline PGI-S category | EKTERLY-treated attacks |
|---|---|
| Mild | 618 (36.2%) |
| Moderate | 685 (40.2%) |
| Severe/very severe | 330 (19.3%) |
*KONFIDENT-S is a multicenter, open-label extension trial of adult and adolescent patients (≥12 years of age; N=134). Study participants had a confirmed diagnosis of HAE and ≥2 attacks within 3 months and were enrolled after completing the KONFIDENT phase 3 trial or de novo.6
†Patients with laryngeal attacks were instructed to treat immediately with conventional on-demand treatment if laryngeal attack symptoms worsened after initial treatment with EKTERLY.10
‡n=32 laryngeal attacks and 533 abdominal attacks. Analysis allowed missing values between consecutive timepoints.6
§Data cutoff September 14, 2024.6
PATIENT SATISFACTION
Patient-reported satisfaction with EKTERLY: an interim analysis from KONFIDENT-S11,*
- In an interim analysis from the KONFIDENT-S 2-year, open-label extension trial, treatment satisfaction was evaluated in patients who switched to EKTERLY from parenteral on-demand therapies
- 61% of attacks were classified as moderate (44%) or worse (17%)
- For each attack, satisfaction with treatment was assessed 24 hours after the first dose of EKTERLY
- Using the 7-point Likert scale ranging from -3 (extremely dissatisfied) to 3 (extremely satisfied), patients responded to the question “overall, how satisfied were you with sebetralstat therapy for this HAE attack?”
84% of patients
reported
being satisfied with EKTERLY
(n=1089 attacks)§
LIMITATIONS
This was an interim analysis, and, therefore, the results should be interpreted with caution. The analysis was conducted retrospectively and cannot be used to demonstrate statistically significant differences between treatment groups.
*KONFIDENT-S is a multicenter, open-label extension trial of adult and adolescent patients (≥12 years of age; N=134). Study participants had a confirmed diagnosis of HAE and ≥2 attacks within 3 months and were enrolled after completing the KONFIDENT phase 3 trial or de novo.6
§Data cutoff September 14, 2024.6
EXPERT INSIGHTS
Hear about the clinical trial design and data for EKTERLY from an industry expert.
“As the first and only oral on-demand treatment, EKTERLY could create a meaningful shift in the way that patients manage their HAE attacks.”
References:
1. EKTERLY. Package insert. KalVista Pharmaceuticals, Inc.; 2025.
2. Riedl MA, Farkas H, Aygören-Pürsün E, et al. Oral sebetralstat for on-demand treatment of
hereditary angioedema attacks. N Engl J Med. 2024;391(1):32-43. doi:10.1056/NEJMoa2314192
3. Riedl MA, Farkas H, Aygören-Pürsün E, et al. Oral sebetralstat for on-demand treatment of
hereditary angioedema attacks. N Engl J Med. 2024;391(1)(suppl 1):1-33.
doi:10.1056/NEJMoa2314192
4. Data on File. KalVista Pharmaceuticals, Inc. 2024.
5. Data on File. KalVista Pharmaceuticals, Inc. 2024.
6. Farkas H, Anderson J, Bouillet L, et al. Long-term safety and effectiveness of
sebetralstat: interim analysis of KONFIDENT-S open-label extension. J Allergy Clin Immunol
Pract. 2025;13(11):3094-3103.e5. doi:10.1016/j.jaip.2025.08.020
7. Bernstein JA, Aygören-Pürsün E, Cancian M, et al. Sebetralstat for on-demand treatment of
mucosal hereditary angioedema attacks in KONFIDENT-S. Clin Transl Allergy.
2025;15(11):e70118. doi:10.1002/clt2.70118
8. Data on File. KalVista Pharmaceuticals, Inc. 2024.
9. Data on File. KalVista Pharmaceuticals, Inc. 2024.
10. Data on File. KalVista Pharmaceuticals, Inc. 2024.
11. Data on File. KalVista Pharmaceuticals, Inc. 2024.