Tyvalzi (sovateltide) / Pharmazz, Sun Pharma, Assertio - LARVOL DELTA

Pharmazz, Inc. Receives U.S. FDA Orphan Drug Designation for Sovateltide for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy (NHIE) (GlobeNewswire)

Orphan drug • Ischemic stroke

Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke (clinicaltrials.gov) - P3 | N=514 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Nov 2026 ➔ Dec 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Sun Pharma Laboratories Limited has received a recommendation from the Subject Expert Committee (SEC) under the Central Drugs Standard Control Organisation (CDSCO) to conduct a Phase IV clinical trial of Sovateltide for Injection 30 µg (Medical Dialogues) - "This came after firm presented Phase-IV Clinical Trial protocol of the drug Sovateltide for Injection 30 μg, (Protocol No. SP/Neurology/Sovateltide/PIV-01-2025, Version No. 1.0; Dated 03 Nov 2025) before the committee. Sovateltide is an endothelin-B receptor agonist used in India for cerebral ischaemic stroke. It has been studied as a treatment alongside standard care for patients with acute cerebral ischaemic stroke....The committee, however, asked the company to remove the control arm and include all patients in the drug arm....Finally, the committee recommended a grant of permission to conduct Phase IV clinical trial as the protocol presented by the firm. In line with the above, the expert panel asked the firm to submit Phase IV clinical trial report to CDSCO for further review by the committee."

New P4 trial • Ischemic stroke

Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke (clinicaltrials.gov) - P4 | N=160 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Mar 2026 ➔ Dec 2026 | Trial primary completion date: Feb 2026 ➔ Sep 2026

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system. (PubMed, Can J Physiol Pharmacol) - "Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation...Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials...This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney..."

Journal • Review • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Ischemic stroke • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • EDN1

Sovateltide at the heart-brain axis crosstalk in Alzheimer's disease: a promising multi-target and cutting-edge therapeutic approach. (PubMed, Inflammopharmacology) - No abstract available

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Real-world functional outcomes of sovateltide as an adjunct to standard therapy in acute ischemic stroke: A prospective observational study. (PubMed, Medicine (Baltimore)) - "These findings represent associations only and do not establish causality. The results offer preliminary real-world insights into the use of sovateltide in AIS, and larger randomized controlled trials are required to determine its independent therapeutic role and to confirm these observations."

Journal • Observational data • Real-world evidence • Cardiovascular • Ischemic stroke

Results from an interim analysis of the multicentric, randomized study of sovateltide (Tycamzzi®) in acute cerebral ischemic stroke patients (ISC 2026) - P3, P4 | "Sovateltide produced a significant improvement in neurological outcomes at 90 days, further confirming results from previous efficacy trials in cerebral ischemic stroke patients. A global Phase III randomized, double-blind, placebo-controlled trial (RESPECT-ETB) (NCT 05691244) is ongoing."

Clinical • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Diabetes • Hematological Disorders • Hypertension • Ischemic stroke • Metabolic Disorders

RESPECT-ETB Phase III Trial to Evaluate Safety and Effectiveness of Sovateltide (Tycamzzi) in Patients with Acute Ischemic Stroke (ISC 2026) - P3 | "The primary endpoint is the proportion of patients achieving mRS 0–2 at day90; secondary endpoints include NIHSS <6, Barthel Index ≥90, with more details at NCT05691244. The trial aims to enroll 514 patients, and the 1 st patient was successfullydosed in July 2025."

Clinical • P3 data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke • DCX • NEUROD1

Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke (clinicaltrials.gov) - P4 | N=160 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Dec 2025 ➔ Mar 2026 | Trial primary completion date: Nov 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Assess Safety and Efficacy of Sovateltide in Hypoxic-ischemic Encephalopathy (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • CNS Disorders

Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke (clinicaltrials.gov) - P3 | N=514 | Recruiting | Sponsor: Pharmazz, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

PMZ-1620 (Sovateltide) in Patients of Acute Spinal Cord Injury (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Jul 2024 ➔ Jul 2026 | Trial primary completion date: Jun 2024 ➔ Jun 2026

Trial completion date • Trial primary completion date • CNS Disorders • Orthopedics

An update of results from the multicentric, randomized study of sovateltide (Tycamzzi®) to treat acute cerebral ischemic stroke patients (ESOC 2025) - P3 | "The patient demographics, NIHSS, ASPECTS, interval between stroke onset and the first treatment dose were similar between the control and the sovateltide groups. More (P=0.0195) patients received thrombolytics in the control group than in the sovateltide group. The co-morbid conditions was similar in the sovateltide and control groups."

Clinical • Late-breaking abstract • Cardiovascular • Ischemic stroke

Targeted Bacteriophage Gene Delivery to Astrocytes Using Intelligent Phagemid-Assembled Gene Expression (iPhAGE) Technology for Neuronal Regeneration (ASGCT 2025) - "Targeting specificity can be enhanced through the incorporation of IRL1620 and EGF ligands into the M13 system...The iPhAGE system's versatility suggests potential applications in other neurological and regenerative medicine contexts, marking a significant advancement in gene therapy technology. Disease Focus of Abstract:Central Nervous System Disorders"

Cardiovascular • CNS Disorders • Gene Therapies • EGFR • NCAM1 • NEUROD1

Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke (clinicaltrials.gov) - P4 | N=160 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Jul 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Nov 2025

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Assess Safety and Efficacy of Sovateltide in Hypoxic-ischemic Encephalopathy (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Pharmazz, Inc. | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Nov 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • CNS Disorders

Intranasal treatment targeting the brain endothelin system attenuates cognitive decline in diabetic rats after ischemic injury (ISC 2025) - "and either a modified Bederson score 10% on Day 3) were randomized to ETA antagonist BQ-123 (3 µg/100 µl PBS), ETB agonist Sovateltide (5 µg/kg), or vehicle intranasal treatment for 3 days per week until 8 weeks post-stroke (n=6-8)... These results suggest that intranasal stimulation of brain ETB receptors or ETA receptor inhibition can prevent the development of progressive cognitive decline after stroke. While further studies are required to better understand how the brain ET system impacts stroke recovery in diabetes, our findings provide novel insights into potential neuroprotective therapies for VCID."

Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Diabetes • Ischemic stroke • Metabolic Disorders

Discovery and development of sovateltide, an endothelin-B receptor agonist to treat cerebral stroke patients (ISC 2025) - "The number of patients with NIHSS of 0-5 at 90 days was 67.95% in control and 85.00% in the sovateltide groups (p=0.0114). The ordinal shift in mRS from 0-1 showed an absolute increase of 8% in the favorable outcome of sovateltide compared to the control group, while a shift in mRS from 0-2 showed an absolute increase of 22% in the favorable outcome of sovateltide compared to the control group.Pharmacologically targeting ET-B receptors with sovateltide is safe and effective in improving neurological outcomes in cerebral ischemic stroke patients."

Clinical • Cardiovascular • Ischemic stroke

Updated results from the multicentric, randomized study of sovateltide (Tycamzzi™) in acute cerebral ischemic stroke patients (ISC 2025) - "Sovateltide produced significant improvement in neurological outcomes at 90 days post-treatment in acute cerebral ischemic stroke patients and suggests imminent efficacy trials."

Clinical • Late-breaking abstract • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Diabetes • Hematological Disorders • Hypertension • Ischemic stroke • Metabolic Disorders • EDN1

Developing Topics. (PubMed, Alzheimers Dement) - "These findings suggest that sovateltide treatment promotes regeneration while simultaneously decreasing the pathology associated with Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Metabolic Disorders • CASP3 • MFN2 • Napsin A • NEUROD1 • SYP

Microglial cell proliferation is regulated, in part, by reactive astrocyte ETBR signaling after ischemic stroke. (PubMed, Exp Neurol) - "In experiments with primary adult astrocytes stimulated by IRL1620, a specific ETBR agonist, we found that ERK1/2 and NFkB mediated the effects of ET on Ang-2 production...In transgenic GFAP-CreER™-EDNRB-fl/fl mice with stroke, conditional knockout of astroglial ETBR significantly decreased the number of proliferating cells in the peri-infarct area with a microglial phenotype (Ki67+/CD11b+). Our results indicate that Ang-2, and possibly other paracrine effectors functioning downstream of astroglial ETBR signaling, are important mediators of microglial cell dynamics after stroke."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology • CX3CR1 • EDNRB • GFAP • ITGAM

Efficacy and Safety of Sovateltide in Patients with Acute Cerebral Ischaemic Stroke: A Randomised, Double-Blind, Placebo-Controlled, Multicentre, Phase III Clinical Trial. (PubMed, Drugs) - P3 | "The sovateltide group had a greater number of cerebral ischaemic stroke patients with lower mRS and NIHSS scores at 90 days post-treatment than the control group. This trial supported the regulatory approval of sovateltide in India, but a multinational RESPECT-ETB trial will be conducted for US approval."

Journal • P3 data • Cardiovascular • Cerebral Hemorrhage • Ischemic stroke

Endothelin-1 potentiated constriction in preeclampsia placental veins: Role of ETAR/ETBR/CaV1.2/CALD1. (PubMed, Placenta) - "The present study firstly demonstrated ET-1 induced greater contraction in preeclampsia placental chorionic plate veins via ETAR/ETBR, instead of via weaker CaV1.2. In utero hypoxia promoted plasma ET-1 in fetal lambs and ewe, similar to that in preeclampsia. ET-1, binding with ETAR/ETBR increased CALD1, which was associated with stronger contraction in preeclampsia. The data provided important information in preeclampsia onset."

Journal • Gynecology • CALD • EDN1

SOVATELTIDE DID NOT INFLUENCE THE THROMBOLYTIC ACTIVITY OF T-PA WHEN USED TO TREAT ACUTE ISCHEMIC STROKE (WSC 2024) - "While t-PA by itself or in combination with sovateltide demonstrated 50% clot lysis within 1-2 hours of incubation, the maximum concentration of sovateltide demonstrated less than 5% clot lysis even after 5 hours of incubation. Conclusions The thrombolytic effect of t-PA is not affected by sovateltide, nor does it possess any thrombolytic activity."

Cardiovascular • Ischemic stroke