Ekterly: A New Hope for Hereditary Angioedema (HAE) Management

• Brand Name : Ekterly
• Generic Name: Sebetralstat
• Drug Class: Plasma Kallikrein Inhibitor
• Form: Oral tablet (300 mg)

Introduction :

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic condition characterized by sudden swelling in various parts of the body. Managing acute attacks has long been a challenge, but a new FDA-approved oral treatment is offering hope. Acterly, the first-of-its-kind oral plasma kallikrein inhibitor, is revolutionizing the way patients are treated for acute HAE attacks. Approval FDA Approves Ekterly (sebetralstat) the First and Only Oral On-demand Treatment for Hereditary Angioedema (HAE) on 8July 2025.

Ekterly(sebetralstat) 300 mg tablets are approved for use in patients 12 years of age and older, providing rapid relief from the swelling, pain, and discomfort associated with HAE.

What Is Ekterly?

Ekterly is the brand name for the active ingredient sebetralstat, which was developed specifically to treat acute HAE attacks. It belongs to a new class of plasma kallikrein inhibitors, which are important in controlling the overproduction of bradykinin, a major cause of inflammation in HAE.

What is Hereditary Angioedema (HAE) ?

Hereditary angioedema (HAE) is a rare, genetic disorder that causes recurrent swelling (angioedema) in various parts of the body, including the skin, gastrointestinal tract, and respiratory tract. It is usually caused by a deficiency or malfunction of the protein C1 esterase inhibitor (C1-INH), which helps control inflammation. HAE is inherited in an autosomal dominant pattern and usually appears in childhood or adolescence. Symptoms include painful swelling, abdominal cramps, and potentially life-threatening airway obstruction. Diagnosis involves blood tests for C1-INH levels and function, along with C4 levels. Treatment options include preventive treatments such as sebetralstat , C1-INH concentrates, and lanadelumab. Management focuses on early diagnosis, avoiding known triggers, and always having emergency treatment available.

Mechanism of Action :

The active ingredient in Acterly, cebetralstat, works by selectively inhibiting the enzyme plasma kallikrein, which is involved in the kallikrein-kinin system (KKS). This system regulates the release of bradykinin, a peptide that increases the permeability of blood vessels and causes tissue swelling.

In patients with HAE, mutations lead to overactivation of plasma kallikrein, which increases bradykinin levels and subsequently causes swelling. Ekterlyhelps to reduce the production of bradykinin, which can:

• Prevent further swelling
• Reduce pain and discomfort
• Reduce the duration of attacks

Indications and Usage :

Ekterly is FDA-approved for the treatment of acute attacks of hereditary angioedema in adults and adolescents 12 years and older.

Not for preventive use:

Ekterly is not designed to prevent future HAE attacks. It is intended only for treating acute symptoms.

Dosage and Administration :

Recommended Dose:

• 300 mg tablet, taken orally at the onset of an HAE attack

Important Considerations:

• Take as soon as symptoms begin
• Swallow tablet whole with water
• Can be taken with or without food

Repeat Dose:

• Only one dose should be taken per attack
• Do not take more than one dose per 24 hours

Clinical Trials and Efficacy :

Clinical Trials and Efficacy

The approval of Ekterly was based on clinical studies that demonstrated:

• Faster symptom relief compared to placebo
• Significant reduction in attack severity
• Improved quality of life in patients using oral therapy vs. injectable options

Key Findings:

• Most patients experienced symptom relief within 1 to 2 hours
• Well-tolerated with minimal side effects
• Oral formulation significantly improved patient adherence and convenience

Benefits of Ekterly :

It stands out in the market for several reasons:

✅ Oral Tablet – No Injection Required

Unlike other HAE treatments that require intravenous or subcutaneous administration, Ekterly is taken orally, making it non-invasive and patient-friendly.

✅ Rapid Onset of Action

Sebetralstat quickly binds to plasma kallikrein, helping to reduce swelling promptly.

✅ Convenience and Portability

Easy to store and carry, Ekterly is ideal for on-the-go treatment, especially in emergency scenarios.

Side Effects of Ekterly :

Like all medications, Sebetralstat may cause some side effects, although not everyone experiences them.

Common Side Effects:

• Headache
• Fatigue
• Nausea
• Abdominal pain

Less Common Side Effects:

• Dizziness
• Skin rash
• Diarrhea

When to Seek Medical Attention:

Contact your healthcare provider immediately if you experience:

• Severe allergic reactions
• Difficulty breathing
• Chest pain
• Swelling in unusual locations

Contraindications and Precautions :

Avoid Sebetralstat if you:

• Have known hypersensitivity to sebetralstat or any ingredients
• Are using other plasma kallikrein inhibitors concurrently

Use with Caution in:

• Pregnant or breastfeeding women (consult physician)
• Patients with liver or kidney disorders

Drug Interactions :

Drug Interactions for Ekterly (Sebetralstat)

While Ekterly (sebetralstat) has a favorable safety profile and minimal known interactions, it’s essential to consider possible drug-drug interactions—especially due to its influence on enzyme systems and transport proteins.

Here are key drug interaction considerations:

1. CYP Enzyme Interactions –

Sebetralstat is not a significant inhibitor or inducer of major cytochrome P450 enzymes. However:

• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) may theoretically reduce sebetralstat levels, potentially lowering efficacy.
• CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase sebetralstat exposure, but clinical significance is likely minimal.

📌 Recommendation: Use caution and monitor clinical response if co-administered with strong CYP3A4 modulators.

2. P-glycoprotein (P-gp) Substrates –

Sebetralstat may inhibit P-gp, a transporter protein involved in drug absorption and excretion.

• Drugs affected: Digoxin, dabigatran, colchicine, and others.
• Effect: Potential increase in blood levels of P-gp substrates, increasing risk of toxicity.

📌 Recommendation: Monitor therapeutic levels and side effects when used with narrow therapeutic index drugs like digoxin.

3. Oral Contraceptives –

Current data does not show significant interaction with estrogen or progesterone-containing contraceptives.

📌 Recommendation: No adjustment required, but always consult a physician if changes in menstrual cycles occur.

4. Food & Supplements

• Food: Ekterly can be taken with or without food. No known interactions with meals.
• Herbal supplements: Avoid concurrent use of St. John’s Wort, as it can induce CYP3A4 and reduce effectiveness.

5. Other HAE Therapies

• Avoid combining Ekterly with other plasma kallikrein inhibitors (like berotralstat or lanadelumab) unless under direct medical supervision.
• C1-esterase inhibitors or bradykinin B2 receptor antagonists (like icatibant) may still be used as part of HAE management but should be spaced appropriately to avoid overlapping effects.

Storage and Handling :

• Store at room temperature (20°C to 25°C)
• Protect from moisture and direct sunlight
• Keep out of reach of children

Why Sebetralstat Matters in 2025 and Beyond :

As we move towards personalized and accessible healthcare, Ekterly is a milestone in the treatment of rare genetic diseases such as hereditary angioedema. Its oral formulation, rapid onset of action and user-friendliness have set a new standard in acute care for HAE.

With continued advancements and widespread availability, Ekterlyhas the potential to significantly improve the lives of thousands of HAE patients globally.

Conclusion :

Ekterly is not just a medicine – it is a lifesaver for patients suffering from unpredictable and painful attacks of hereditary angioedema. Its ease of use, rapid onset of action, and non-invasive formulation make it a game-changing therapy in the management of acute HAE.

If you or someone you know is living with hereditary angioedema, consult a healthcare provider to see if Ekterly might be an appropriate treatment during acute attacks.

Frequently Asked Questions (FAQs)

Disclaimer: This blog post is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making any medical decisions.