Utilization of Inj. Sovateltide: A novel injectable formulation

Dhivya Selvaraj¹, Bini Susan Isaac²

¹Consultant – Neurology, Kauvery Hospital, Salem

²Senior Clinical Pharmacologist, Kauvery Hospital, Salem

Abstract

Sovateltide, a highly selective endothelin-B receptor agonist and synthetic analog of endothelin-1, is a neural progenitor cell therapeutic agent for the treatment of acute cerebral ischemic stroke (ACIS), hypoxic-ischemic encephalopathy (HIE), spinal cord injuries and Alzheimer’s disease. In May 2023, sovateltide was approved in India for the treatment of cerebral ischemic stroke within 24 hr of stroke onset. This study explores the pharmacokinetics, efficiency, and safety profile of injection in managing Cerebral Ischemic Stroke.

Methods: Observational Retrospective study in a Tertiary Care Hospital.

Conclusion: The drug demonstrates significant therapeutic potential for managing Cerebral Ischemic Stroke, with a favourable safety profile. The result suggests that it may offer an effective and well tolerated option for patients with inadequate responses. Further studies are recommended to explore long term efficiency and safety.

Inj. Sovateltide – Drug Profile

Sovateltide, a novel injectable formulation, is a highly selective endothelin-B receptor agonist and synthetic analog of endothelin-1, is a neural progenitor cell therapeutic agent for the treatment of acute cerebral ischemic stroke (ACIS), hypoxic-ischemic encephalopathy (HIE), spinal cord injuries and Alzheimer’s disease. In May 2023, sovateltide was approved in India for the treatment of cerebral ischemic stroke within 24 h of stroke onset

Brand Name	Inj. Tyvalzi
Dose	30 Mcg
Manufacture	Sun Pharma
Cost	Rs.1300
Approved by FDA	2/10/2023
Indication	Cerebral Ischemic stroke
Contraindication	Hypersensitivity
Drug Interactions	No drug interactions observed in Clinical Phase I,II,III studies
Pregnancy	No maternal or fetal toxicity
Lactation	Caution should be exercised when drug is administrated to nursing mother
Geriatrics	No drug related adverse event reported
Undesirable Effects	Uneasiness, sweating, abdominal discomfort and vomiting at a dose of 0.9 mcg/kg body weight
Overdose	All these symptoms are short lasting (approx 10 min) and resolve without medical intervention.

Mechanism of Action

Stimulates neural progenitor cells
Produces neurovascular remodelling by forming new neurons and blood vessels following cerebral ischemic stroke
It also increases blood flow, It has apoptotic activity, It protects neural mitochondria and enhances their biogenesis.

Pharmacokinetics

Absorption – IV (Intravenous)

Distribution – Tissues

Metabolism – In Vitro metabolism, 83–85% of protein bind in the protein binding assay

Excretion – Urine

Storage and handling instruction – 2 to 8° C, protect from light.

Highlights of Dose and Administration

Dose	3 Mcg/kg of body weight /dose
Reconstitution solution	Sodium Chloride Injection IP (0.9 %w/v)
Dosing Interval	3 hr ± 1 hr
Total doses in a day	3 doses
Total doses	9 (3 doses on each day- Day 1, 3, 6)
First Dose	Within 24 hr of the onset of the stroke

Side effects

Fatigue
Headache
Nausea
Dizziness

Quick Tips

The formulation is a first in class drug to treat acute cerebral ischemic stroke.
It can be given upto 24 hr after the onset of symptoms.

Data collection

This is an observational retrospective study in a tertiary care hospital on the utilization of the injection

Time Period: Jan 2024–August 2024 (8 months) – 41 patients
Data Source: HMS and MRD

Results and discussion

1. Gender

Gender	No. of patients
Male > 60	14
Male < 60	13

Gender	No. of patients
Female >60	9
Female <60	5

2. Age group

Age Group	No. of Patients
Less than 60	20
Greater than 60	21

3. Risk factors

Risk Factors	No.of patients
ACS/CAD	1
OLD CVA	1
COPD/DM/POST CABG	1
DM	6
DM/HTN	1
DM/HTN/CAD POST-PTCA	1
DM/HTN/Hypothyroidism	1
DM/CKD	1
DM/HTN	4
DM/HTN/CAD/OLD CVA	1
DM/HTN/OLD CVA	1
HTN	7
HTN/CKD	1
HTN/DM	1
NIL	11
OLD CVA/HTN	1
DM/HTN/Hypothyroidism	1

S. No.	MRI
1	Acute infarct in left PCA territory
2	Left ACA territory infarct
3	Acute thick subdural hemorrhage
4	Brain with Angiogram done showed Acute infarcts in right corona radiata, fronto parietal and temporal regions /Mild diffuse cerebral atrophy with prominent sulci /Focal severe luminal narrowing in M1 segment of right middle cerebral artery /Reduced flow signal in rest of the right middle cerebral artery and its branches.
5	Acute -CVA (ischemic stroke), Left hemiplegia,Type II diabetes mellitus ,Systemic hypertension ,Hypothyroidism,Normal LV function ,Autoimmune cause ? vasculitis ,Anemia (corrected)
6	CVA (ischemic stroke),DM/HTN ,CAD / Post PTCA ,Splenic infarct
7	Acute CVA/Ischemic stroke
8	Acute CVA ; right hemipons infarct with left hemiplegia and speech disturbances , hyperhomocysteinemia/denovo detected hypertension
9	Acute CVA ; left ventral medulla infarct wigh right hemiparesis and speech disturbances,uncontrolled DM - II
10	Acute CVA ; left corona radiata infarct with right umn facial palsy and slurred speech,hyperhomocysteinemia
11	CVA/Ischemic stroke ,HTN
12	sHTN/TIA (recurrent)
13	Acute CVA; left ventromedial thalamic infarct with right hemiparesis & speech disturbances , denovo-detected hypertension
14	Type II diabetes mellitus ,Systemic hypertension ,Acute CVA
15	HTN / CVA ,Ischemic stroke
16	DM, Acute CVA, Right thalamic infarct fracture ,Thrombolysis done with Inj. Tenectase
17	Type II DM, Accelerated hypertension ,CVA left thalamic infarct ,Thrombolysed with Inj. Tenectase
18	DM / HTN,CVA/ Ischemic Stroke
19	Traumatic left side neck soft - tissue injury , acute CVA ; right cervical ICA free - floating thromus with right MCA / ACA territories patchy infarcts ; left hemiplegia, hyperhomocysteinemia / denovo DM - II
20	Acute CVA; left ICA / MCA large vessel occlusion with moderate -sized infarct ; global aphasia with right hemiplegia ,hyperhomocyteinemia
21	DM ,CVA ,Ischemic stroke ,Post thrombolysis
22	HT,CVA , Ischemic stroke , Right thalamic infarct ,Post thrombolysis
23	Systemic hypertension ,Obesity ,CVA ,Ischemic stroke Right MCA territory infarct
24	Acute CVA, Ischemic stroke, Right hemiparesis
25	Acute CVA ,Ischemic stroke

CT scan and Diagnosis

S. No.	CT Scan and Diagnosis
1	Acute CVA ; right thalamic infarct with left sided face & upper limb sensory disturbances ,- hyperhomocysteinemia
2	Recurrent CVA ; multiterritorial acute infarcts; right MCA & left PCA - territories ,- hyperhomocysteinemia / uncontrolled DM ,denovo detected CKD
3	Acute CVA ; left corona radiata infarct with right hemiplegia,- AKI/ Hyperhomocysteinemia
4	Acute CVA; left ICA / right ACA territory infarcts; ? hypoxia brain injury ,AF with CVR ; cardio-embolic stroke, uncontrolled DM II / accelerated HTN
5	Fracture left neck of femur ,CVA
6	Acute CVA ; left MCA M1/2 occlusion with right hemiplegia and global aphasia , hypercholesterolemia/hyperhomocysteinemia/accelerated HTN, stable CKD stage - IV
7	Acute CVA; right corona radiata / periventricular infarct with left hemiparesis , hyperhomocysteinemia
8	Diabetes Mellitus ,CVA - (Post Circulation Stroke ) - Left PCA Territory Infarct
9	Diabetes Mellitus ,CVA - (post circulation stroke ) - left PCA territory infarct
10	Acute CVA ; right thalamic infarct with left sided upper limb weakness & clumsiness ,denovo detected CKD / Hypercholesterolemia / Homocysteinemia ,Hypovitaminosis D
11	HTN, Acute CVA,? Reno- parenchymal HTN, Vitiligo vulgaris
12	HTN,CKD on HD,IE of MV - severe MR + vegetation + severe PAH - Need MVR, Left ACA territory infarct - (Thrombolysed with Tenectase) improved ,Pulmonary edema
13	Acute CVA ; left ventral pontine infarct with right hemiplegia and speech disturbances , hypercholesterolemia
14	Recurrent CVA ; left corona radiata sub acute infarct with right hemiparesis , dehydration with pre - renal AKI
15	Systemic hypertension ,CVA - Left hemiparesis,ACS - Unstable angina ,Normal LV function
16	Acute CVA ; right frontal acute infarcts with left lower limb > upper limb weakness ,dehydration with pre oxonal AKI ; UTI , hyperhomocysteinemia / hypercholesterolemia
17	Acute CVA ; left hemiplegia ,hypercholesterolemia
18	DM,CKD on HD, SDH, Multifocal acute infract, Right Hemiplegia
19	ACUTE CVA ; right fronto - temporo - parietal large infarct with left hemiplegia , post CABG status with moderate LV dysfunction, COPD lung with recurrent bronchospasm episodes
20	Acute infarct in right MCA territory
21	Multiple sub acute lacunar infarcts in left fronto parietal lobe at left MCA, ACA water shed territory
22	Multi focal acute lacunar infarcts in right fronto - perietal lobes ,Chronic lacunar infarcts in right corona radiata / central semi ovale
23	Focal acute infarct in right high fronto parietal lobe adjacent to central sulcus / peri rolandic region
24	Acute infarct in right basal ganglia
25	Small vessel ischemic changes
26	Patchy acute infarcts in watershed areas of left parieto occipital region ,Diffuse cerebral atrophy with small vessel ischemic changes
27	Focal area of acute infarct in left thalamocapsular region
28	Multiple acute lacunar infarcts in left superior and inferior cerebellum
29	Free floating thrombus at right ICA region ; right MCA / ACA territory multifocal acute patchy infarcts
30	Small area of mild diffusion restriction in right corona radiata and ganglio capsular region - Acute infarct
31	Right MCA tenitory infarct
32	Left MCA territory infarct
33	Multi focal patchy areas of acute infarcts in right fronto - parietal, centri semiovale, occipital and temporal lobes

4. Mortality status

Mortality Status	No. of patients
Alive	37
AMA	4

Conclusion

Our study, observed that in the Male age group greater than 60 (14), 34.1% received Inj. Sovalteltide, and Female age group greater than 60 (9), 21.95%.
Major modifiable risk factors were HTN, DM, HTN/DM and few patients developed stroke without any risk factor.
37 patients were symptomatically improved and discharged well.
No side effects were reported so far.

Limitations of the study

Other Risk factors like Smoking, alcohol not included in this study.

This study do not provide the evidence of a Case-Control study or Randomized Controlled Trials.

Dr. Dhivya Selvaraj
Consultant – Neurology

Dr. Bini Susan Isaac
Senior Clinical Pharmacist

Utilization of Inj. Sovateltide: A novel injectable formulation

Utilization of Inj. Sovateltide: A novel injectable formulation

Dhivya Selvaraj1, Bini Susan Isaac2

Journals

Dhivya Selvaraj¹, Bini Susan Isaac²