Milestone Achieved: Pitolisant Phase III Clinical Trial for Excessive Daytime Sleepiness in Chinese OSA Patients Completes Full Patient Enrollment
On April 17, 2023, Langhua Group announced in Shenzhen that its subsidiary, Langhua Pharmaceuticals, had conducted in ChinaTivoliGen Successfully Completes Full Patient Enrollment in Phase III Clinical Study on Obstructive Sleep Apnea. This is a large-scale, randomized, double-blind, placebo-controlled, multicenter Phase III clinical study evaluating the efficacy and safety of TivoliGen Hydrochloride Film-Coated Tablets in treating excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA)., With this, the enrollment of all 240 target patients in the study has been completed, marking a significant milestone in the development of tiptolixant in China. It is poised to become the first non-controlled substance approved in China for improving excessive daytime sleepiness associated with obstructive sleep apnea (OSA).
Obstructive sleep apnea (OSA) is a disease characterized by recurrent episodes of apnea and hypopnea during sleep due to partial or complete obstruction of the upper airway, leading to frequent hypoxemia and arousals, which in turn trigger a series of clinical pathophysiological complications. Common symptoms include snoring, apnea, and excessive daytime sleepiness (EDS). Pitolisant is a novel, highly selective, potent, orally active histamine H3 receptor antagonist/inverse agonist that has been approved and widely used in Europe and the United States due to its excellent safety and efficacy. Pitolisant enhances histaminergic transmission in the brain, demonstrating a strong wake-promoting effect. It also modulates various other neurotransmitter systems, including increasing the release of acetylcholine, norepinephrine, and dopamine, which further enhances its efficacy in improving excessive daytime sleepiness. In September 2021, the European Medicines Agency (EMA) approved pitolisant for the treatment of excessive daytime sleepiness caused by OSA.Pitolisant is also currently the only non-controlled substance approved worldwide for this indication.
This study was initiated by Langhua Pharma, with clinical endpoints designed in accordance with international standards. A total of 25 clinical research centers were established across 16 provinces, municipalities, and autonomous regions in China. The clinical dosing regimen involved pitolisant versus placebo. The primary objective of the study was to evaluate the efficacy of pitolisant hydrochloride film-coated tablets in treating excessive daytime sleepiness in subjects with obstructive sleep apnea, while the secondary objectives were to assess the improvement in quality of life and the safety profile of this product in subjects with obstructive sleep apnea.
Ye Jingying
Lead Investigator, Chairman of the Sleep Medicine Professional Committee of the Chinese Medical Doctor Association, Professor at Beijing Tsinghua Changgung Hospital, Tsinghua University
“Although nasal continuous positive airway pressure (nCPAP) is the first-line treatment for obstructive sleep apnea (OSA), there remains a significant unmet therapeutic need for patients who are intolerant of or refuse CPAP therapy, or who continue to experience excessive daytime sleepiness (EDS) despite CPAP treatment. As clinicians, we share our patients’ hope for more effective treatment options to help alleviate symptoms, reduce the risks associated with EDS, and improve quality of life. We are encouraged by the completion of enrollment in the Phase III clinical trial of pitolisant. We will continue our efforts to conduct subsequent treatment and follow-up in accordance with the study protocol, striving to bring new treatment options to patients as soon as possible.”
He Ruyi
Advisor to Langyu Group; Former Chief Scientist at the Center for Drug Evaluation, National Medical Products Administration
“The completion of patient enrollment in the clinical trial for OSA-related excessive daytime sleepiness marks a breakthrough in the development of tiptofant in China and a significant milestone in the field of pharmacological treatment for excessive daytime sleepiness in the country. With patient recruitment now successfully concluded, we eagerly anticipate favorable outcomes from the clinical trial and hope that the Langyu team will continue to accelerate both clinical development and commercialization efforts.”To ensure that China’s first non-psychotropic controlled new drug for treating OSA-related excessive daytime sleepiness benefits patients as soon as possible.”
Xiang Yu
Chief Executive Officer of Langyu Group
“Excessive daytime sleepiness (EDS) is a primary symptom of obstructive sleep apnea (OSA), affecting more than half of OSA patients. EDS significantly increases the risk of hospitalization due to motor vehicle accidents, severely impairs patients’ quality of life, and adds to the socioeconomic burden. The harms associated with excessive daytime sleepiness urgently require greater public awareness. Through this clinical trial, Langyu Group has fully appreciated Shenzhen’s support and encouragement for innovation in biopharmaceutical R&D. We are pleased to have leveraged Shenzhen’s first-class resources in clinical trial services to accelerate patient recruitment. As the final hospital for patient recruitment in this trial, Shenzhen People’s Hospital served as the second-largest patient enrollment site nationwide, fully demonstrating “Shenzhen Speed” and “Shenzhen Efficiency.” In the future, our group will further increase investment and resource allocation in Shenzhen, accelerating new drug development. By fully leveraging Shenzhen’s favorable policies and clinical advantages, we strive to achieve regulatory approval and market launch of drugs developed locally in Shenzhen at an early date.”
Yu Jing
Deputy Director of the Shenzhen Municipal Development and Reform Commission
“The Shenzhen Municipal Committee of the Communist Party of China and the Shenzhen Municipal People’s Government attach great importance to the development of the biopharmaceutical industry. To address the pain points of ‘insufficient R&D capabilities and a scarcity of innovative drugs,’ we encourage the provision of drug clinical trial services. It is gratifying that the last patient has been enrolled in the clinical trial for OSA-related excessive daytime sleepiness in Shenzhen. Shenzhen will implement the decisions and deployments aimed at achieving high-quality development of the biopharmaceutical industry, continue to foster an innovation ecosystem for biopharmaceuticals, accelerate the cultivation of biopharmaceutical industry clusters, provide stronger support for innovative enterprises, and promote the high-quality development of the industry.”
About Pitolisant
Tirzepatide is a selective histamine H3 receptor inverse agonist that has received orphan drug designation from both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), and has been designated as a breakthrough therapy by the FDA. Tirzepatide was approved by the EMA in 2016 and by the FDA in 2019 for the treatment of narcolepsy in adults, with or without cataplexy. In September 2021, the EMA approved tirzepatide for the treatment of excessive daytime sleepiness caused by obstructive sleep apnea (OSA). In January 2023, the EMA approved tirzepatide for the treatment of narcolepsy with or without cataplexy in children and adolescents aged 6 years and older. Tirzepatide submitted a New Drug Application (NDA) to the China National Medical Products Administration in September 2021 for the treatment of narcolepsy.
Over the years since its market launch, pitolisant has gained widespread clinical recognition for its excellent safety and efficacy. Pitolisant is the only non-controlled substance approved globally for the indication of narcolepsy and is concurrently recommended by guidelines in the United States, Europe, and China. In the Chinese Guidelines for the Diagnosis and Treatment of Narcolepsy (2022 Edition), pitolisant is recommended as a first-line treatment for narcolepsy and is considered capable of simultaneously improving excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and nighttime sleep disturbances. Furthermore, pitolisant is recommended as the preferred therapeutic agent for excessive daytime sleepiness in a broad sense in the Expert Consensus on Clinical Diagnosis and Treatment of Excessive Daytime Sleepiness, published by the Chinese Medical Journal.
Langyu GroupCommitted to becoming China’s most leading rare disease company, we aim to provide comprehensive and sustainable support to patients and families affected by rare diseases by building China’s first rare disease ecosystem. Langyu Group currently has two subsidiaries: “Langhua Pharmaceuticals,” which focuses on the research, development, and commercialization of rare disease drugs, and “Zi’ang Health,” which provides medical solutions for a wide range of rare disease patients and their families. Langyu Group was jointly founded by globally leading healthcare funds F-Prime Capital, Vivo Capital, and STIC Investments, and completed an $80 million Series A financing round in July 2020.
Langhua PharmaceuticalsIt is a company dedicated to the research, development, and commercialization of drugs for rare diseases. It aims to establish a comprehensive rare disease product platform by developing and introducing effective and affordable therapies, thereby supporting and accelerating scalable commercialization efforts. Langhua Pharmaceuticals currently focuses on neurological, endocrine, and metabolic disorders. Its pipeline includes eight rare disease drug candidates: four are at the stage of having submitted or preparing to submit New Drug Applications (NDAs), while four independently developed rare disease drugs are currently in the preclinical stage.
Zi'ang HealthIt is a health technology company dedicated to leveraging cutting-edge technologies to build China’s and the world’s largest patient-centric open ecosystem service platform. Zi’ang Health utilizes internet-based digital tools, big data, and artificial intelligence technologies to enhance awareness of rare diseases, promote disease screening and diagnosis, implement full-cycle disease management, and explore various payment innovations, thereby providing comprehensive, end-to-end, one-stop healthcare solutions for rare disease patients and their families in China. Zi’ang Health’s current business scope includes: Rare Disease Think Tank, Rare Disease Internet Hospital, AI-enabled patient identification, AI Cloud Classroom, patient empowerment, and innovative payment solutions.