Hereditary angioedema (HAE) is a rare and potentially life-threatening condition that causes unpredictable swelling in the skin, gastrointestinal tract, and airways. For years, on-demand HAE treatments were limited to injectable options — delaying symptom relief for many patients.

In July 2025, the U.S. FDA approved EKTERLY (sebetralstat), the first oral plasma kallikrein inhibitor specifically developed to treat acute HAE attacks in patients aged 12 and above.

This blog post provides a clinician-focused overview of EKTERLY’s mechanism of action, dosing, clinical trial data, safety profile, and regulatory status in the U.S. and India.

What is EKTERLY (Sebetralstat)?

EKTERLY is a novel oral treatment for managing acute attacks of hereditary angioedema (HAE). Unlike conventional injectable therapies, EKTERLY enables patients to initiate treatment immediately at symptom onset, helping reduce swelling more rapidly.

Key Highlights:

• First oral on-demand therapy for HAE
• Targets the plasma kallikrein pathway, a central trigger of HAE attacks
• Developed by KalVista Pharmaceuticals

Also Read: ANDEMBRY (Garadacimab-gxii): A New Dawn in Preventing Hereditary Angioedema Attacks

Indications & Patient Eligibility

FDA-Approved Indication:

• Treatment of acute HAE attacks in adults and adolescents aged 12 years and older

Population Studied:

Age Group	Status
≥12 years	Approved; included in clinical trials (12–68 yrs)
<12 years	Not studied; safety and efficacy not established
≥65 years	Limited data; use clinical discretion

Contraindications:

• None currently listed according to the FDA-approved label

How EKTERLY Works: Mechanism of Action

Sebetralstat is a reversible inhibitor of plasma kallikrein — a key enzyme in the cascade that leads to bradykinin release. Bradykinin is responsible for increased vascular permeability, which causes the painful swelling episodes seen in HAE.

By blocking kallikrein, sebetralstat:

• Stops the overproduction of bradykinin
• Rapidly reduces tissue swelling
• Interrupts the positive feedback loop of kallikrein activation

Dosing and Administration

Standard Regimen:

• 600 mg orally at first sign of an HAE attack (2 x 300 mg tablets)
• A second dose may be repeated after 3 hours, if needed
• Maximum: 1,200 mg/day

Administration Notes:

• Take orally with or without food
• High-fat meals do not affect absorption
• Swallow tablets whole (do not crush or chew)

Dose Adjustments in Special Populations

Condition	Dosing Recommendation
Strong CYP3A4 inhibitors	Avoid use
Moderate CYP3A4 inhibitors	300 mg dose; may repeat after 3 hours
Moderate hepatic impairment (Child-Pugh B)	Reduce dose to 300 mg
Severe hepatic impairment (Child-Pugh C)	Contraindicated
Mild renal or hepatic impairment	No adjustment needed

Clinical Trial Evidence: KONFIDENT Phase 3 Study

EKTERLY’s approval is based on data from the KONFIDENT trial, a multicenter, placebo-controlled, double-blind study assessing sebetralstat’s effectiveness in treating acute HAE attacks.

Study Details:

• 110 patients (12–68 years)
• 264 attacks treated with:
  • EKTERLY 600 mg
  • EKTERLY 300 mg
  • Placebo

Primary Endpoint:

Time to start of symptom relief (patient-reported as “a little better” on two consecutive assessments)

Group	Median Time to Relief	% Achieving Endpoint in 12 Hours
EKTERLY 600 mg	2.0 hours	76%
Placebo	Not reached	49%

Other Findings:

• Symptom reduction started at about 9.1 hrs (600 mg)
• Full resolution within 24 hrs in 49% of patients vs. 27% (placebo)
• “Much better” on PGI-C achieved faster: 4.6 hrs vs. 9.5 hrs

Pediatric & Geriatric Use

• Adolescents (12–17 years): Comparable efficacy and safety to adults
• Older Adults (≥65 years): Limited trial data; use clinical judgment

Safety & Adverse Events

Most Common Side Effects (≥2%):

Adverse Reaction	EKTERLY 600 mg	Placebo
Headache	3.2%	1.2%

No other events occurred more frequently than placebo.

Warnings and Precautions

• QT Interval Prolongation: Observed at high doses (up to 10.4 ms increase)
• Drug Interactions:
  • Strong CYP3A4 inhibitors (↑ drug levels): Avoid
  • CYP3A4 inducers (↓ efficacy): Avoid
  • Acid-reducing agents: May lower absorption
• Hepatic Impairment:
  • Moderate (Child-Pugh B): Dose reduction needed
  • Severe (Child-Pugh C): Contraindicated

Pharmacokinetics Snapshot

Parameter	Value
Tmax	~1 hour post-dose
Half-life	5.3 – 8.9 hours
Metabolism	CYP3A4 (major), CYP2C8 (minor)
Protein Binding	~77%
Excretion	63% feces, 32% urine

Regulatory Status

United States

• FDA Approved: July 2025 (NDA 219301)
• Indication: Acute HAE attacks in patients ≥12 years

India

• Not yet approved (as of August 2025)
• No CDSCO registration or DCGI notification
• HAE drugs may enter India via Form 44 or import registration pathways

Manufacturer & Product Info

• Company: KalVista Pharmaceuticals, Cambridge, MA, USA
• Product: EKTERLY 300 mg oral tablets
• Packaging: 4 blister cards (child-resistant)
• Storage: 20–25°C; excursions 15–30°C permitted

Comparison: EKTERLY vs Other HAE Therapies

Feature	EKTERLY (Sebetralstat)	Berinert / Cinryze	Firazyr (Icatibant)	Ruconest
Route	Oral	IV	Subcutaneous	IV
Use	Acute	Acute/Prophylaxis	Acute	Acute
Age Approved	≥12 yrs	Varies	≥18 yrs	≥13 yrs
Administration	Self-administered at home	Home/Clinic IV	Self-injection	Clinic/Home
Common AE	Headache	Varies	Injection site pain	Varies

Frequently Asked Questions (FAQs)

Clinical Insight

“Oral therapies like EKTERLY offer practical advantages for patients who can’t access injectables in time. As the treatment landscape shifts, especially in India, accessibility and affordability will remain key factors.”
— Dr. R. Mehta, Clinical Immunologist, Mumbai

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Conclusion

EKTERLY (sebetralstat) brings a significant shift in how acute hereditary angioedema is managed — offering a rapid, oral alternative to injections. For healthcare professionals in India and the U.S., this represents not just a new treatment option, but a broader opportunity to improve patient access and adherence.

Stay updated on regional approvals, and always consult full prescribing info before recommending EKTERLY.

An Interactive infographic on the Ekterly Drug

References

1. US FDA Prescribing Information: EKTERLY (sebetralstat), July 2025. NDA 219301.
2. Longhurst, H.J., et al. “Hereditary angioedema: modern approaches to management.” National Library of Medicine, 2019;381:1136-1148.
3. Craig, T., et al. “Acute and prophylactic management of hereditary angioedema: a 2020 practice parameter update.” Ann Allergy Asthma Immunol. 2020;124(6):600-622.
4. KalVista Pharmaceuticals. “EKTERLY Product Website.” Accessed August 2025.
5. US National Library of Medicine: DailyMed. “Sebetralstat (EKTERLY) Label.” Accessed 2025.