Sovateltide in Cerebrovascular Accident (CVA)
Sovateltide (Tycamzzi™) is an approved treatment for acute cerebral ischemic stroke in India that significantly improves functional outcomes when administered within 24 hours of stroke onset, with a 22.67% absolute increase in patients achieving functional independence (mRS 0-2) at 90 days compared to standard care alone. 1
Mechanism and Rationale
Sovateltide is a highly selective endothelin-B (ETB) receptor agonist that works through three key mechanisms:
- Increases cerebral blood flow to ischemic regions 2, 3
- Provides anti-apoptotic neuroprotection to salvage penumbral tissue 2, 3
- Promotes neurovascular remodeling and neural repair 2, 3
Evidence Base
The approval is supported by two major clinical trials demonstrating both safety and efficacy:
Phase III Trial (2024)
- Primary outcomes: 22.67% more patients achieved mRS 0-2 (OR 2.75,95% CI 1.37-5.57) and 17.05% more achieved NIHSS 0-5 (OR 2.67,95% CI 1.27-5.90) at 90 days in the sovateltide group 1
- Functional improvement: 72.50% of sovateltide patients versus 51.28% of controls showed ≥2-point improvement on mRS (OR 2.50,95% CI 1.29-4.81) 1
- Safety profile: Intracranial hemorrhage rates were identical between groups (8.75% sovateltide vs 8.97% control), with no drug-related adverse events 1
Phase II Trial (2021)
- Complete recovery: Significantly more patients achieved complete recovery (NIHSS 0 and Barthel Index 100) with sovateltide 2
- Quality of life: Improved EQ-5D and Stroke-Specific Quality of Life scores at 90 days 2
- Early functional gains: Improvement in mRS and Barthel Index by day 6 (p<0.0001), not seen in placebo group 2
Clinical Application
Patient Selection
Administer sovateltide to patients meeting these criteria:
- Age 18-78 years 1
- Radiologically confirmed acute ischemic stroke 1
- Presenting within 24 hours of symptom onset 1, 4
- NIHSS score ≥6 at presentation 1
Exclusions
Do not use sovateltide in:
- Recurrent stroke patients 1
- Patients receiving endovascular therapy 2, 1
- Intracranial hemorrhage on imaging 2, 1
Dosing Protocol
Administer sovateltide 0.3 µg/kg 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 0.9 µg/kg) 2, 1
Timing Considerations
- Optimal administration occurs around 18 hours post-stroke onset based on trial data 1
- The 24-hour window is the approved timeframe, though earlier treatment within 20 hours was common in trials 2
Integration with Standard Care
Sovateltide is administered in addition to standard stroke care, not as a replacement 2, 1. Standard care should include:
- Antiplatelet therapy: Aspirin (50-325 mg/day), aspirin plus extended-release dipyridamole, or clopidogrel 5
- Stroke unit care: Organized interdisciplinary care reduces mortality by 14% (OR 0.86,95% CI 0.76-0.98) 5
- Risk factor management: Aggressive control of hypertension, diabetes, and hypercholesterolemia 6
Safety Profile
Sovateltide demonstrates excellent tolerability:
- No drug-related adverse events in either trial 2, 1
- No effect on hemodynamic, biochemical, or hematological parameters 2
- Hemorrhagic transformation rates equivalent to placebo 1
Clinical Pitfalls and Caveats
Critical timing: While the approved window is 24 hours, trial data suggest most benefit when administered closer to 18 hours post-onset 1. Do not delay administration unnecessarily.
Imaging requirement: Radiologic confirmation of ischemic stroke is mandatory before administration to exclude hemorrhagic stroke 1, 4.
Endovascular therapy: Sovateltide trials specifically excluded patients receiving endovascular therapy 2, 1. The drug should not be used in this population until further data are available.
Geographic availability: Currently approved only in India 4. A multinational RESPECT-ETB trial is ongoing for US FDA approval 1.
Rehabilitation Integration
Following sovateltide treatment, implement evidence-based cognitive rehabilitation: