Sovateltide Dosing for Acute Ischemic Stroke
The recommended dosing regimen of sovateltide (TYVALZI, IRL-1620) for adult patients with acute ischemic stroke is 0.3 µg/kg administered intravenously as a bolus over 1 minute, given in three doses at 3 ± 1 hour intervals on Days 1,3, and 6 (total daily dose of 0.9 µg/kg on each treatment day), initiated within 24 hours of stroke onset. 1, 2
Dosing Protocol
Administration Schedule:
- Dose: 0.3 µg/kg per administration 1, 2
- Route: Intravenous bolus over 1 minute 2
- Frequency: Three doses per treatment day, separated by 3 ± 1 hour intervals 1, 2
- Treatment Days: Day 1, Day 3, and Day 6 after randomization 1, 2
- Total Daily Dose: 0.9 µg/kg on each of the three treatment days 2
Timing of Initiation
- Treatment window: Must be initiated within 24 hours of stroke symptom onset 1, 2
- Median time to first dose: Approximately 18 hours after stroke onset in clinical trials 1
- Optimal timing: Earlier administration within the 24-hour window may be preferable, with 14-20 hours being typical in trial populations 2
Patient Selection Criteria
Inclusion parameters based on regulatory approval studies:
- Age 18-78 years 1
- Radiologically confirmed acute cerebral ischemic stroke 1, 2
- National Institutes of Health Stroke Scale (NIHSS) score ≥ 6 at presentation 1
- Presenting within 24 hours of symptom onset 1, 2
Exclusion criteria:
Integration with Standard of Care
Sovateltide is administered as an adjunct to standard stroke care, not as a replacement for established therapies. 3, 2 This means:
- Intravenous thrombolysis with alteplase should still be administered when indicated and not contraindicated 3
- Mechanical thrombectomy for large vessel occlusions remains the priority intervention when appropriate 3
- Standard supportive care including blood pressure management, glucose control, and antiplatelet therapy (aspirin 160-325 mg started 24-48 hours post-stroke if not receiving thrombolysis) should continue 4
Safety Profile
- Hemodynamic stability: Sovateltide does not affect blood pressure, heart rate, or other hemodynamic parameters at therapeutic doses 2
- Hemorrhage risk: Intracranial hemorrhage rates were similar between sovateltide (8.75%) and control groups (8.97%) in Phase III trials 1
- Tolerability: No drug-related adverse events were reported in clinical trials 2
- Laboratory parameters: No effects on biochemical or hematological parameters 2
Clinical Context and Evidence Quality
The dosing regimen is based on a Phase III randomized, double-blind, placebo-controlled trial that led to regulatory approval in India 1. This represents the highest quality evidence available for sovateltide dosing. The trial demonstrated:
- 22.67% absolute increase in patients achieving modified Rankin Scale (mRS) 0-2 at 90 days (OR 2.75) 1
- 17.05% absolute increase in patients achieving NIHSS 0-5 at 90 days (OR 2.67) 1
- 51.28% vs 72.50% of patients showing ≥2 point improvement on mRS (OR 2.50) 1
Important Caveats
Current guideline limitations: The American Heart Association/American Stroke Association guidelines do not specifically mention sovateltide, as they state that no neuroprotective agents have demonstrated efficacy in improving stroke outcomes (Class III: No Benefit; Level of Evidence A for neuroprotective agents in general) 3. However, this reflects the guideline publication date predating sovateltide's Phase III trial completion.
Geographic availability: Sovateltide has received regulatory approval in India but is not yet approved in the United States 1. A multinational RESPECT-ETB trial is planned for US FDA approval 1.
Mechanism distinction: Unlike traditional neuroprotective agents that have failed in stroke trials, sovateltide works through endothelin-B receptor agonism to increase cerebral blood flow, provide anti-apoptotic effects, and promote neurovascular remodeling 1, 2, 5, 6. This mechanistic difference may explain its clinical efficacy where other neuroprotective strategies have failed.