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Teprotumumab (Tepezza): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment

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Abstract

Teprotumumab (TPT) is a type I insulin-like growth factor receptor inhibitor, marketed as Tepezza; recently USFDA approved it for the treatment of thyroid eye disease (thyroid-associated ophthalmopathy (TAO), Graves ophthalmopathy/orbitopathy) in the USA. It is a monoclonal antibody although it was initially developed in collaboration with Genmab and Roche for the treatment of the tumour, but later it was investigated by River Vision Development Corporation and Horizon Therapeutics for its ophthalmic use. The drug has been designated as an orphan drug, breakthrough designation and fast-track designation. This review summarizes the milestones in the research and development including ongoing, clinical trial of TPT till now, foremost to this primary approval for thyroid-associated ophthalmopathy (TAO).

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Abbreviations

AUC:

Area under the curve

AUCSS :

Area under the curve at steady state

BLA:

Biologics license application

C max :

Maximum serum concentration of the drug

C min :

Minimum serum concentration of the drug

C Trough :

Trough concentration

CCL5:

Chemokine ligand 5

DLT:

Dose-limiting toxicities

DME:

Drug metabolizing enzymes

GLP:

Good laboratory practices

IGF-1:

Insulin-like growth factor 1

IL-6/8:

Interleukin

MTD:

Maximum tolerated dose

OFs:

Orbital fibroblasts

RES:

Reticuloendothelial system

RVDC:

River Vision Development Corporation

t 1/2 :

Half-life of the drug

T max :

Time at which maximum serum concentration of the drug observed

TED:

Thyroid eye disease

TNF-α:

Tumour necrosis factor-α

TSH:

Thyroid-stimulating hormone

USFDA:

Food and Drug Administration

V D :

Volume of distribution

V SS :

Volume of distribution at steady state

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Acknowledgements

The authors wish to express their gratitude to Botswana Medicines Regulatory Authority, Gaborone, Botswana.

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Authors and Affiliations

  1. Laboratory Services, Botswana Medicines Regulatory Authority (BoMRA), Plot 112, International Finance Park, Gaborone, Botswana

    Faraat Ali

  2. School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Sector 3, Pushp Vihar, New Delhi, 110017, India

    Anushma Chorsiya

  3. Department of Pharmaceutical Sciences, Lingayas Vidyapeeth, Nachouli, Faridabad, Haryana, India

    Varisha Anjum

  4. Department of Chemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India

    Asad Ali

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FA and VA contributed to the conception and design. The first draft of the manuscript was written by AC, and all authors commented on previous versions of the manuscript. All authors read, approved and permitted the final manuscript.

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Correspondence to Faraat Ali.

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Ali, F., Chorsiya, A., Anjum, V. et al. Teprotumumab (Tepezza): from the discovery and development of medicines to USFDA approval for active thyroid eye disease (TED) treatment. Int Ophthalmol 41, 1549–1561 (2021). https://doi.org/10.1007/s10792-021-01706-3

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