Chinese-developed Long-acting Growth Hormone Eftansomatropin Alfa Achieves Annual Height Gain of 10.76 cm in Phase III Trial; BLA Accepted by NMPA

On December 9, Tianjing Biotechnology and Jumpcan jointly announced that the National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for Itan Long-Acting Recombinant Human Growth Hormone Injection (hereinafter referred to as “Itan Long-Acting Growth Hormone”) for the treatment of Pediatric Growth Hormone Deficiency (PGHD).

"As the first and only long-acting fusion protein growth hormone in both the domestic application stage and among marketed products, this innovative therapy is expected to provide a safe, effective, and convenient once-weekly dosing treatment option for children with growth hormone deficiency."

Etan Growth Hormone is a long-acting growth hormone developed by Genexine. Its mechanism of action involves replacing endogenous human growth hormone, stimulating hepatocytes to promote the synthesis of insulin-like growth factor 1 (IGF-1) in the liver, thereby increasing serum IGF-1 levels. Through IGF-1, it activates osteoblasts and chondrocytes in various tissues, further promoting skeletal growth and development.

In October 2015, Tasgen, a subsidiary of Tasly (later acquired by Tianjing Biotechnology), entered into an agreement with Genexine to obtain the Chinese rights to itan pegylated recombinant human growth hormone. On November 10, 2021, Tianjing Biotechnology and Jumpcan held a strategic cooperation signing ceremony, reaching a strategic partnership for the development, production, and commercialization of Tianjing Biotechnology’s itan pegylated recombinant human growth hormone. Reportedly, the total value of this cooperation reached RMB 2.016 billion, setting a new high in recent years for similar transactions in China’s biopharmaceutical market and the global pediatric pharmaceutical sector.

In China, one of the greatest challenges facing approximately 3.4 million children with growth hormone deficiency is the treatment burden associated with existing short-acting formulations requiring daily injections. Multiple studies have shown that over 30% of patients using these daily injection regimens miss doses on a weekly basis, which significantly compromises patient adherence and therapeutic efficacy.

Yitan long-acting growth hormone utilizes innovative hyFc@ fusion protein technology, which significantly enhances the drug's stability and half-life by combining human growth hormone with a specially designed human immunoglobulin.This patented technology achieves long-acting pharmacological effects of growth hormone in vivo while ensuring its biological activity., thereby making ItanThe First Once-Weekly Fusion Protein Long-Acting Growth Hormone, providing patients with safer, more effective, and more convenient treatment options.

In the completed Phase III registrational clinical study (CTR20202305),Itan Long-Acting Growth Hormone Demonstrates Superior Efficacy and Safety:

• Eftansomatropin long-acting growth hormone achieved the primary endpoint after 52 weeks of treatment, demonstrating non-inferiority compared with the positive control drug (Norditropin®, a daily-administered growth hormone formulation).

  
  

• Eutane long-acting growth hormone is administered once weekly, with an annualized height velocity (AHV) of 10.76 cm/year in pediatric patients, versus Norditropin®, which is administered once daily with an AHV of 10.28 cm/year; the between-group difference was 0.47 (95% confidence interval: -0.06, 1.00; p<0.0001).

  
  

• Safety results showed that Yitan long-acting growth hormone was well tolerated, with no discontinuations due to treatment-related adverse events; its safety profile was comparable to that of the comparator drug, Norditropin®.

It is reported that Itran, a long-acting growth hormone, is the most advanced drug candidate in Tianjing Biotechnology’s pipeline. According to current estimates, following its marketing application submission and with the support of Jumpcan in the pediatric channel, the drug’s peak annual sales are projected to reach between RMB 3 billion and RMB 5 billion.

Pediatric Growth Hormone Deficiency (PGHD) is an endocrine disorder that severely impairs children's growth and development, primarily caused by insufficient secretion of growth hormone from the pituitary gland. Clinical manifestations in affected children include short stature and metabolic abnormalities, and may even lead to psychosocial disorders, cognitive deficits, and poor quality of life.

Since its initial application in 1958, growth hormone has undergone five generations of development. Currently, the market offers three types of growth hormone products: short-acting growth hormone (lyophilized powder for injection), short-acting growth hormone (aqueous solution for injection), and long-acting growth hormone (aqueous solution for injection). Among these, the treatment of children with growth hormone deficiency primarily relies on daily injections of short-acting formulations. Approximately 22% of pediatric patients miss at least four doses per month, which significantly compromises therapeutic efficacy.

The vast Chinese human growth hormone market remains largely untapped, offering substantial growth potential.According to a report by Frost & Sullivan, there are currently an estimated 3.4 million pediatric patients with growth hormone deficiency in China, yet less than 5% receive standardized treatment, highlighting a substantial disease burden and treatment gap.

Currently, the treatment of pediatric growth hormone deficiency primarily relies on daily injections of short-acting formulations. Approximately 22% of patients miss at least four doses per month, which significantly compromises therapeutic efficacy. The development of more convenient dosing regimens is of great significance for improving treatment adherence and enhancing patients’ quality of life.

The Chinese growth hormone market has experienced rapid development in recent years, with its market size growing from $600 million in 2018 to $1.7 billion in 2022, representing a compound annual growth rate (CAGR) of 29.3%. By 2022, China’s share of the global market had reached 34%, surpassing the United States to become the world’s largest market. Driven by increased treatment rates, earlier intervention, and the transition to weekly injection regimens, the Chinese growth hormone market is projected to continue its growth trajectory, reaching an estimated $4.8 billion by 2030.

Furthermore, according to a Frost & Sullivan report, patients in developed countries not only initiate treatment earlier than those in China, but also have an average treatment duration of over 3.5 years, compared to approximately 1.7 years for Chinese patients. Clinical guidelines and consensus recommendations suggest that growth hormone therapy should be initiated as early as possible for children with growth hormone deficiency. However, among children actually receiving treatment in China, 70% are aged 10–13 years. Considering both treatment costs and the efficacy of growth promotion, the optimal window for treating short stature is generally between 3 and 12 years of age. This indicates that a significant number of Chinese patients are either not being treated during the optimal therapeutic window or are experiencing delays in treatment initiation.

Currently, multiple growth hormone products have been approved for marketing in China, including Eutropin (LG Chem), Ansomone (Anke Biotechnology), Norditropin (Novo Nordisk), and GenSci Pro (GeneScience Pharmaceuticals).

Among them, Jinsei Pharmaceutical’s polyethylene glycol recombinant human growth hormone injection (brand name: Jinsai Zeng) is the world’s first PEGylated long-acting growth hormone formulation and the only long-acting growth hormone product marketed in China. The product was approved for marketing in China in January 2014, with an indication for slow growth in children caused by endogenous growth hormone deficiency, and a dosing frequency of once weekly. In August 2024, the indications for Jinsai Zeng were expanded to include slow growth in children caused by endogenous growth hormone deficiency and growth disorders in children due to congenital ovarian dysgenesis syndrome (Turner syndrome).

Currently, GenSci’s Jinseizeng is the only long-acting formulation approved for marketing in China. This high-potential blue-ocean market is ripe for competition. Among competitors, Anke Biotechnology has submitted its production application, Tianjing Biotechnology has filed for marketing approval, and Ascendis Pharma and Amoytop Biotech, among others, have all entered Phase III clinical trials. A new round of market competition is imminent.

After decades of exploration, the development of long-acting growth hormone has gradually broken through technical bottlenecks and entered a harvest period. This vast blue-ocean market with huge potential is being gradually unlocked. The story of growth hormone will continue.

References:

The Growth Hormone Battle: Product Superiority vs. Channel Dominance – VCBeat