Pro-heal Pharmaceuticals Completes First-in-China Dosing in Phase I Clinical Trial of PHP1003, the Nation's First Homegrown IGF1R Antibody for Thyroid Eye Disease

On October 26, 2022, the first subject was enrolled and dosed in a clinical trial of an IGF-1R antibody drug for the treatment of thyroid-associated ophthalmopathy (TAO), conducted by Suzhou Pulukang Pharmaceutical at Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. This clinical study is a randomized, double-blind, placebo-controlled Phase I trial evaluating the safety, tolerability, pharmacokinetics, and immunogenicity of PHP1003 in healthy adult subjects in China, involving both single and multiple ascending doses. On June 30, 2022, the Investigational New Drug (IND) application for PHP1003 injection officially received implicit approval from the National Medical Products Administration (NMPA). PHP1003 is the first domestically developed Class 1 innovative IGF-1R antibody drug to enter clinical trials in China. The PHP1003 injection features an innovative subcutaneous administration route, which mitigates certain adverse effects associated with drugs targeting this pathway, thereby providing patients with more convenient medication management and a safer treatment option.

Thyroid-associated ophthalmopathy (TAO), also known as thyroid eye disease (TED), is a common extra-thyroidal clinical manifestation of Graves' disease. It is a specific autoimmune disorder triggered by autoantigens expressed by thyroid epithelial cells, orbital adipocytes, and fibroblasts. The condition primarily presents with symptoms such as proptosis, diplopia, strabismus, orbital pain, eyelid swelling, eyelid retraction, and lagophthalmos, which can severely affect facial appearance and lead to visual impairment. This disease can also occur in patients with hypothyroidism and those with normal thyroid function. The prevalence of TAO is approximately 0.1%–0.3%, with a significantly higher incidence in women than in men. The disease is classified into an active phase and a quiescent phase based on its progression. For many years, there has been a lack of safe and effective pharmacological treatments. Currently, the mainstay of treatment for the active phase in China includes high-dose corticosteroids and immunosuppressants, which can alleviate inflammation during the active phase to some extent but are associated with significant adverse effects and low patient acceptance. In the quiescent phase, orbital adipose connective tissue has undergone fibrotic changes and becomes insensitive to medical therapy; therefore, patients primarily rely on surgical intervention in the later stages. However, the disease is prone to recurrence after surgery, potentially necessitating multiple procedures.

Teprotumumab, marketed by Horizon Therapeutics under the brand name TEPEZZA, is the first monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) for the treatment of thyroid-associated ophthalmopathy (TAO). It is also the first marketed drug targeting the insulin-like growth factor-1 receptor (IGF-1R). Its development path was highly convoluted. Initially developed as an anticancer agent, it failed to demonstrate significant clinical efficacy in oncology but confirmed its safety profile. Researchers at the University of Michigan discovered that fibroblasts around the orbits of TAO patients exhibited high expression of IGF-1R. In 2012, teprotumumab entered clinical trials for the treatment of thyroid-associated ophthalmopathy. The program subsequently progressed smoothly: it received FDA Fast Track designation in 2015, Breakthrough Therapy designation in 2016, and Orphan Drug designation in 2019, culminating in accelerated FDA approval for marketing in the United States in January 2020. Unlike other biologics used in TAO management, such as anti-CD20 antibodies, which primarily alleviate inflammation, TEPEZZA not only reduces inflammation but also effectively decreases proptosis.

Thyroid eye disease is classified as a rare disease in the United States, with an estimated patient population of approximately 200,000. At launch, Horizon Therapeutics projected first-year sales of only $40 million; however, actual sales exceeded $800 million within less than a year of its market debut. In 2021, despite having no production capacity in the first quarter due to the pandemic, annual sales still reached $1.6 billion. With peak sales projected at $3.5 billion, this fully demonstrates the market potential of this antibody drug for treating thyroid eye disease, establishing it as one of the most successfully developed rare-disease drugs in history.

Suzhou Pro-heal Pharmaceuticals Co., Ltd. (Pro-heal Pharmaceuticals), registered in 2019 and located in the BioBAY biomedical industrial park within Suzhou Industrial Park, is committed to becoming a leading innovator in ophthalmic pharmaceuticals. The founder studied under Academician Wu Zuoze and U.S. National Academy of Sciences member Eric Goaux, and previously worked at renowned pharmaceutical companies such as Allergan and Johnson & Johnson, contributing to the market launch or late-stage clinical development of multiple new drugs. The co-founder studied under U.S. National Academy of Sciences member Richard Goodman and held positions at Merck, Quest, and Pfizer, accumulating extensive experience in R&D and clinical trial management. Pro-heal develops novel drugs closely aligned with clinical needs and insights into ocular immune mechanisms. Several candidate drugs with innovative mechanisms for treating ophthalmic diseases are sequentially entering clinical trials, providing patients with additional therapeutic options for unmet medical needs.