Takeda's Eligard® (Leuprorelin Acetate Microspheres for Injection) 3-Month Formulation Approved in China for Central Precocious Puberty

Shanghai, August 11, 2020 /PRNewswire/ --Takeda China AnnouncesEnantone under its portfolio^®(Leuprorelin Acetate for Injection, Microspheres) 3-month formulation (strength: 11.25 mg) has been officially approved by the China National Medical Products Administration for the treatment of Central Precocious Puberty (CPP). This is Enantone.^®(Leuprorelin Acetate for Injection Microspheres) The third indication approved in China for the 3-month dosage form, and the first 3-month sustained-release long-acting formulation officially approved nationwide for the treatment of CPP. Enantone^®(Leuprolide Acetate Microspheres for Injection) The frequency of clinical visits required for the 3-month formulation is consistent with the monitoring frequency for gonadotropin-releasing hormone agonist (GnRHa) therapy stipulated in the Chinese "Consensus on Diagnosis and Treatment of Central Precocious Puberty (2015)." Meanwhile, it reduces the number of injections from 12 times per year for the 1-month formulation to 4 times per year. Its approval will provide a more convenient option for standardized continuous treatment of central precocious puberty (CPP), helping to further improve treatment adherence and satisfaction among pediatric patients, as well as enhance the quality of life for their families.

Central Precocious Puberty (CPP) is a common pediatric endocrine disorder characterized by the premature activation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to rapid development of internal and external genitalia and the emergence of secondary sexual characteristics before the age of 8 in girls and 9 in boys.^[1]. Epidemiological surveys indicate that the prevalence of central precocious puberty (CPP) among children in China has been on the rise in recent years.^[2], with its incidence rising year by year, it has become a focus of social concern. Currently, the prevalence of central precocious puberty (CPP) among children in China is approximately 0.43%, with about 350,000 affected children nationwide.^[3]. The effects of CPP on the body are mainly manifested as follows: premature sexual development leads to early menarche in girls; accelerated skeletal maturation results in bone age exceeding chronological age and premature epiphyseal closure, thereby affecting the child's final adult height; premature development of secondary sexual characteristics and sexual maturity may lead to corresponding psychological issues or abnormal social behaviors, severely impacting the physical and mental health of children.^[4]。

Takeda ChinaApplied to the China National Medical Products Administration in 2020 to add Enantone.^®(Leuprorelin Acetate for Injection, Microspheres) The 3-month formulation is indicated for the treatment of Central Precocious Puberty (CPP). The recent application for this new indication was approved within just three months from submission, fully demonstrating the National Medical Products Administration of China’s attention to and support for pediatric medications.

This approval is based on four clinical studies evaluating the efficacy and safety of the 3-month formulation of leuprorelin acetate microspheres for injection in the treatment of central precocious puberty (CPP): LEUb/CPP3M14/TIF; TAP/III/96/023; L-CP07-167; and L-CP07-177. The clinical study results demonstrated that the 3-month formulation of leuprorelin acetate microspheres for injection (strength: 11.25 mg) effectively suppresses the hypothalamic-pituitary-gonadal axis and exhibits a favorable safety profile.

Professor Luo Xiaoping, Vice Chairman of the Pediatric Branch of the Chinese Medical Association, Project Leader for Quality Control of Child Growth and Development in China, and Director of the Department of Pediatrics at Tongji Hospital affiliated with Tongji Medical College of Huazhong University of Science and Technology, stated: “The treatment of central precocious puberty (CPP) generally requires a duration of 2–3 years. The 3-month formulation of leuprorelin acetate microspheres for injection will provide a more convenient treatment option for children with CPP requiring long-term therapy, thereby helping to promote standardized long-term management of CPP. Meanwhile, the 3-month formulation can effectively reduce injection-related fear and injection-site reactions associated with short-acting formulations used in CPP treatment. It also mitigates the adverse impacts on disease management caused by factors such as regular monthly school absences by patients and work absences by parents for hospital visits, thus improving the quality of life for both patients and their families.”

Professor Fu Junfen, Executive Deputy Director of the National Clinical Research Center for Children’s Health and Diseases, Head of the Endocrinology, Genetics and Metabolism Group of the Pediatric Branch of the Chinese Medical Association, and Executive Deputy President of the Children’s Hospital Affiliated to Zhejiang University School of Medicine, pointed out: “In the face of health management challenges in the post-pandemic era, multiple stakeholders should jointly explore new models for the development of pediatric diagnosis and treatment, and flexibly ensure that affected children receive scientific, continuous, and standardized effective therapy through long-acting and convenient treatment regimens. The approval of the three-month formulation of leuprorelin acetate microspheres for injection for the treatment of central precocious puberty (CPP) will provide a new direction for safe and effective continuous treatment.”

Leuprorelin Acetate Microspheres for Injection are GnRH agonists that exert therapeutic effects on sex hormone-dependent diseases by suppressing the hypothalamic-pituitary-gonadal axis.^[5]. Clinical studies have shown that leuprolide acetate microspheres can stably and continuously reduce sex hormone levels.^[6]Previously, Takeda’s leuprorelin acetate for injection (microspheres), one-month formulation (strengths: 1.88 mg and 3.75 mg), had been approved in China for nearly 22 years for the treatment of central precocious puberty (CPP), providing therapy to more than 100,000 Chinese pediatric patients.

^[1]Subspecialty Group of Endocrinology, Hereditary and Metabolic Diseases, the Society of Pediatrics, Chinese Medical Association. Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2015).
^[2]Writing Group for the Puberty Development Survey and Research of the Endocrinology, Genetics, and Metabolism Subgroup, Pediatric Branch, Chinese Medical Association. Chinese Journal of Endocrinology and Metabolism. 2010;26.
^[3]"China Statistical Yearbook 2016."
^[4]Ke Jiangwei (review), Duan Rong (proofreader). "Research Progress on Precocious Puberty and Its Risk Factors." Experimental and Laboratory Medicine, June 2016, Vol. 30, No. 3.
^[5]See the package insert.
^[6] J Clin Endocrinol Metab, May 2012, 97(5):1572–1580. Efficacy and safety of Leuprolide Acetate 3-Month Depot 11.25 Milligrams for the Treatment of Central Precocious Puberty