From India to the World: The Rise of Sovateltide in Stroke Recovery

Shahid Akhter, Consulting Editor, FEHealthcare,  spoke to Prof. Anil Gulati, Founder Director & Chairman, Pharmazz and also Emeritus Professor at Midwestern University and the University of Illinois, Chicago, to know more about Sovateltide’s clinical success in India and its promising Phase 3 U.S. and global trial progress.

What are the key challenges and emerging opportunities in stroke care today? 

Acute cerebral ischemic stroke causes damage to brain tissues, which may lead to disabilities or death. The incidence of brain stroke is increasing, particularly in the younger population. In 2021 alone, 93.8 million people were living with stroke, and 11.9 million new cases occurred worldwide. 

Clot-breaking medications such as tissue plasminogen activator (tPA) and surgical procedures such as stentrievers can restore blood flow to the brain, minimizing the impact of a stroke but with limited success. There has not been a new FDA-approved non-thrombolytic therapy for stroke in over 30 years. Therefore, continuous efforts are underway to develop better therapies. However, due to the complex pathophysiology of stroke, the development of a new promising drug is challenging, as evident by the failure of several agents in late-stage clinical trials. 

We have shown promising results in our previous Phase 3 study, which showed that sovateltide (brand name Tyvalzi) could be a meaningful advance over the standard of care to promote a fast recovery and improve neurological outcomes in cerebral ischemic stroke patients. 

 

Sovateltide was introduced in India in 2023. What has the clinical response been so far? Can you also update us on the progress and expectations around the pending Phase 3 trial in the U.S.?

In a Phase 3 study of 158 patients in India, Sovateltide showed statistically significant and clinically meaningful results demonstrating improvements in key neurological outcomes.

Sovateltide was approved in India in May 2023 for cerebral ischemic stroke, and an exclusive sales, marketing, and distribution agreement for India was executed with Sun Pharmaceuticals, who launched sovateltide in India under its brand name Tyvalzi on September 14, 2023. Over 60,000 patients have been treated to date since the commercial launch in India.

The US Food and Drug Administration (FDA) has given the go-ahead to initiate the Phase 3 study. In addition, a Special Protocol Assessment agreement was reached with the FDA for the Phase 3 trial of sovateltide to treat cerebral ischemic stroke. The Phase 3 clinical trial is designed for a total of 514 stroke patients at 65 sites in the US, Germany, Spain, Australia, and the UK. The primary endpoint is the proportion of patients demonstrating functional independence post-stroke, defined as a modified Rankin Scale (mRS) score of 0–2 at 90 days after stroke onset. Pharmazz has now enrolled and treated its first patient in the Phase 3 RESPECT-ETB (ClinicalTrials.gov ID: NCT05691244). 

 

Could you elaborate on Sun Pharma’s investment in Pharmazz? How does this strategic partnership impact the roadmap for Sovateltide and other pipeline candidates?

The potential for new indications of sovateltide is being constantly explored by Pharmazz. A trial for hypoxic-ischemic encephalopathy is under way to determine the efficacy of sovateltide in this disease condition, which has no treatment except for hypothermia. Another indication of where Pharmazz is conducting clinical research is the treatment of Alzheimer’s disease using sovateltide.

Another drug, Centhaquine, is a frontline therapy used along with the standard of care and is well-positioned to meet a critical unmet need as a pharmacologically active resuscitative agent. A decrease in the volume of blood circulation from blood or fluid loss due to trauma, gastrointestinal bleeding, major surgery, postpartum hemorrhage, diarrhea, or vomiting can cause hypovolemic shock. About 1.9 million people worldwide die because of hemorrhagic shock every year, most dying within the first 6 hours. Centhaquine activates venous alpha2B adrenergic receptors to increase cardiac preload and activates central alpha2A adrenergic receptors to decrease cardiac afterload. Thereby, Centhaquine converts the venous unstressed blood volume to stressed blood volume and improves cardiac output and blood circulation, making it an ideal candidate for the resuscitation of patients with hypovolemic shock. 

 

How does Pharmazz plan to navigate regulatory and market challenges in expanding into international territories, particularly the U.S. and Europe?

Pharmazz, Inc., has made significant steps in its clinical programs for Sovateltide across the U.S., Europe, the UK, and Australia. A leading CRO has been engaged to manage the multicenter, randomized, double-blind, placebo-controlled trial involving 514 patients. Regulatory approvals have been received from the EMA, and IRB approvals are underway. Clinical sites in the U.S., EU, UK, and Australia are preparing for patient enrollment. Pharmazz has now enrolled and treated its first patient in the Phase 3 RESPECT-ETB (ClinicalTrials.gov ID: NCT05691244). 

 

With rising interest in neuroprotective agents, how do you envision Sovateltide’ s positioning in a competitive and evolving global stroke care landscape?

There remains a tremendous medical burden of ischemic stroke, with only a minority of patients who obtain functional independence and very few novel interventions in development. The new mechanism of action of sovateltide (Tyvalzi) is likely to prove greatly beneficial to the patients. The feedback from numerous neurologists and stroke specialists is that patients with cerebral ischemic stroke are responding much better and are showing quicker recovery. This feedback corroborates with the finding of the clinical trials we have conducted.

Building a team with a lack of financial resources was a difficult task, and a small group of persons had to work extremely hard. Now that Sun Pharma has provided significant investment in Pharmazz, we are in a position to attract talented persons. However, a challenge that we are likely to face is the lack of talent to deal with different regulatory agencies across the world.