Shanghai, November 3, 2022 – Luye Pharma Group today announced that Ruoxinlin^® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets), its innovative drug for treating Major Depressive Disorder (MDD), has been approved for launch in China by the National Medical Products Administration (NMPA). Ruoxinlin^® is China’s first class 1 innovative chemical drug independently developed locally for the treatment of MDD and protected by intellectual property rights. The launch of the product represents a major breakthrough for innovative drugs developed in China in this field.

 

 

Clinical studies show that Ruoxinlin^® is able to comprehensively and stably improve depressive symptoms, including significantly reducing anxiety and retardation/fatigue, relieving anhedonia, improving cognition, and facilitating faster social recovery of patients. In addition, the drug does not cause somnolence and has no significant impacts on sexual functioning, bodyweight, and lipid metabolism, demonstrating a favorable safety profile and good tolerability. 

Professor Zhang Hongyan from Peking University Sixth Hospital, principal investigator of Ruoxinlin^®, said: “The approval of Ruoxinlin^® marks a solid step forward for Chinese pharmaceutical companies in developing new antidepressant drugs and represents a milestone in the history of psychiatric drug development in China. Ruoxinlin^® demonstrates clinical pharmacodynamic features that can comprehensively alleviate multiple symptoms of MDD, especially in terms of improving anxiety, anhedonia, fatigue, and cognition. It provides a new option for clinicians in treating MDD.”

A long-awaited breakthrough in treating MDD

MDD has a high incidence rate, a high recurrence rate, and a high disability rate. Data from the World Health Organization shows that globally about 3.8% of the people suffer from MDD¹, and China’s latest epidemiological survey indicates that 3.4% of the people in the country are living with MDD, which means that China has around 50 million MDD patients who need to treat with standard medications². The relapse rate of MDD is as high as 50%-85%, and 50% of the relapses would happen within 2 years after the onset of the disease³. Consequently, MDD has become a significant burden on the family life of the patients and their social productivity.

Patients can generally benefit from existing antidepressants, but they still have major unmet needs such as low remission rates and residual symptoms, which mainly include anxiety, cognitive impairment, fatigue, and anhedonia. Those symptoms severely impair their social functioning and precipitate relapses^4-7. In addition, current treatments often cause adverse reactions, such as sexual dysfunction, weight gain, emotional retardation, and somnolence, resulting in poor medication compliance, an important reason for poor prognosis^{8, 9}.

Authoritative MDD treatment guidelines both in China and abroad define the goal of treatment as “achieving full remission, reducing risk of relapse, alleviating functional impairment, and enhancing quality of life”. In other words, patients need to be treated for all symptoms, including emotional, somatic and cognitive symptoms. Developed to fulfill that goal, Ruoxinlin^® is expected to become a better therapy for MDD patients and facilitate their social recovery. 

Comprehensively improving MDD symptoms through a multiple reuptake inhibiting mechanism 

The results of the mechanism of action (MOA) for Ruoxinlin^® were published in Frontiers in Pharmacology^10,11. The Phase II clinical trial results were published in International Journal of Neuropsychopharmacology¹² and presented at the 19th National Psychiatry Conference of the Chinese Medical Association. And the Phase III clinical trial results were presented at the 2022 Annual Meeting of the American Psychiatric Association. The preclinical MOA studies on Ruoxinlin^® show that it is a serotonin (5-HT)-norepinephrine (NE)-dopamine (DA) reuptake inhibitor (SNDRI). Neurotransmitters 5-HT, NE, and DA are closely associated with MDD¹³. Compared with existing selective 5-HT reuptake inhibitors and 5-HT/NE reuptake inhibitors, SNDRI increases the intervention of DA, which promises a greater synergy between the therapeutic agents and a more comprehensive improvement of MDD symptoms; and the additional benefit of elevating DA also helps alleviate the adverse reactions caused by the decrease in DA as a result of increased 5-HT levels14.

The approval of Ruoxinlin^® is based on six completed clinical studies in China. Among them, the multicenter, randomized, double-blind, placebo-controlled Phase III study designed to evaluate the efficacy and safety of the drug shows that, after eight weeks of treatment, Ruoxinlin^® was markedly superior to the placebo in terms of the change of the mean Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the baseline, the change of the mean 17-item Hamilton Depression Scale (HAM-D17) total score from the baseline, the MADRS response rate, the MADRS remission rate, the HAM-D17 response rate, the HAM-D17 remission rate and the change of the mean Hamilton Anxiety Rating Scale total score from the baseline. Furthermore, compared with the placebo, better results with statistical significance for the drug were also observed in improving anhedonia, retardation, cognitive impairment, and fatigue. These features give Ruoxinlin^® an edge over  traditional antidepressant drugs. In addition, Ruoxinlin^® also demonstrated a favorable safety profile and good tolerability: it did not cause somnolence, nor did it impact sexual functioning, body weight, or lipid metabolism. 

Dr. Tian Jingwei, R&D Project Leader of Ruoxinlin^®, Vice President of Non-Clinical Research and Head of New Drug Discovery at Luye Pharma Group, said: “MDD has complex and multifaceted symptoms, and a multi-targeted approach can make antidepressants more effective and safer. Ruoxinlin^® is an SNDRI-based antidepressant, which has been validated by both lab research and confirmatory clinical studies. It can comprehensively improve patients' symptoms, facilitate their social recovery, and facilitate their early return to family and work.”

Leveraging CNS expertise to address the unmet needs

Yang Rongbing, President of Luye Pharma Group, said: “MDD has become one of the most prevalent mental disorders in China, causing a heavy burden on patients, their families, and the entire society. The approval of Ruoxinlin^® is very exciting to us. Our company is already well prepared for its commercialization. We will leverage our expertise in the central nervous system(CNS) therapeutic area to bring this new treatment option to patients as soon as possible.”

CNS diseases, MDD included, are one of the strategic focuses for Luye Pharma. In this therapeutic area, over the years, the company has been trying to build a portfolio of innovative products, to develop its in-house sales & marketing team, and to expand its market share including penetrating into lower-tier markets. Its CNS products now are sold to nearly 3,000 hospitals in China. The approval of Ruoxinlin^® further expands its CNS portfolio, and helps to generate a bigger synergy between the company's existing resources and strengths and improve its commercial operations.

###

About Ruoxinlin^®

Ruoxinlin^® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets) is a “Class 1 innovative drug” developed by Luye Pharma Group on its New Therapeutic Entity/New Chemical Entity platform. Preclinical studies show that Ruoxinlin^® works as an Serotonin-Norepinephrine-Dopamine Reuptake Inhibitor (SNDRI) for the treatment of Major Depressive Disorder. Clinical studies show that the efficacy of Ruoxinlin^® may be attributed to its inhibition of the reuptake of multiple monoamine neurotransmitters. In addition, the Phase III clinical trials for the drug for the treatment of Generalized Anxiety Disorder are under way. 

References: