Sovateltide in Stroke Management
Sovateltide is not currently recommended for routine clinical use in stroke management as it lacks sufficient evidence and is not included in current stroke treatment guidelines. 1
Current Status of Sovateltide
- Sovateltide (also known as IRL-1620 or PMZ-1620) is an endothelin-B receptor agonist that has been investigated as a potential neuroprotective agent for acute ischemic stroke 2
- While recent Phase III clinical trial data from India shows some promising results, sovateltide is not yet approved by major regulatory bodies worldwide except in India (where it received approval under the brand name Tycamzzi™) 3
- Current American Heart Association/American Stroke Association (AHA/ASA) guidelines do not include sovateltide among recommended treatments for acute ischemic stroke 1
Proposed Mechanism of Action
- Sovateltide acts as an agonist at endothelin-B receptors and is proposed to work through several mechanisms 4:
Clinical Evidence for Sovateltide
A Phase III randomized, double-blind, placebo-controlled trial in India (2024) reported that sovateltide when added to standard care showed 3:
- 22.67% higher proportion of patients with favorable modified Rankin Scale (mRS) scores (0-2) at 90 days compared to control group
- 17.05% more patients achieved National Institutes of Health Stroke Scale (NIHSS) scores of 0-5 at 90 days
- No significant difference in adverse events between sovateltide and control groups
An earlier Phase II trial (2021) showed 2:
- Improvement of ≥2 points on mRS in 60% of sovateltide patients vs. 40% in control group
- Improvement of ≥40 points on Barthel Index in 64% of sovateltide patients vs. 36% in control group
- No drug-related adverse events were reported
Current Guideline Recommendations for Stroke Management
- AHA/ASA guidelines emphasize the following approaches for acute ischemic stroke 1:
- Reperfusion therapies (IV thrombolysis and/or endovascular thrombectomy) remain the mainstay of acute treatment
- Neuroprotective agents have shown disappointing results in clinical trials despite promising preclinical data 1
- The administration of vasodilatory agents is not recommended for treatment of patients with acute ischemic stroke (Class III; Level of Evidence A) 1
Limitations and Considerations
- Current evidence for sovateltide comes primarily from studies conducted in India with relatively small sample sizes 2, 3
- A multinational trial (RESPECT-ETB) is planned for potential US approval 3
- Most neuroprotective agents have failed to translate preclinical success to clinical benefit in stroke patients 1
- The AHA/ASA guidelines note that "newer agents and innovative clinical trial designs that adhere to the STAIR (Stroke Therapy Academic Industry Roundtable) criteria are needed to demonstrate that neuroprotective strategies could be helpful in treatment of stroke" 1
Clinical Implications
- Sovateltide should not be used as a substitute for established acute interventions such as IV thrombolysis or endovascular thrombectomy 1
- Until further definitive evidence is available from large multinational trials, sovateltide should be considered experimental 1, 3
- Clinicians should continue to follow established guidelines for stroke management, which focus on rapid reperfusion therapies and supportive care 1
Future Directions
- The planned RESPECT-ETB multinational trial may provide more definitive evidence regarding sovateltide's efficacy and safety 3
- If proven effective in larger trials, sovateltide could potentially address an important unmet need for neuroprotective therapies in stroke 6
- Research is also investigating sovateltide's potential applications in other neurological conditions including Alzheimer's disease, spinal cord injury, and neonatal hypoxic-ischemic encephalopathy 6