Shanghai, November 11, 2024 - Luye Pharma Group today announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved its Investigational New Drug (IND) application for LY03021 for the treatment of Major Depressive Disorder (MDD). LY03021 is designated as a Class 1 innovative drug in China.
LY03021 is an inhibitor of the norepinephrine transporter (NET) and the dopamine transporter (DAT) as well as a gamma-aminobutyric acid type A receptor-positive allosteric modulator (GABAAR PAM). Developed on Luye Pharma’s New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform, this investigational antidepressant works on the three targets above, a novel mechanism of action (MoA) that no other investigational drugs currently under development have been publicly reported to employ, making LY03021 a potential first-in-class drug.
MDD is a mood disorder characterized by significant and persistent depressive symptoms impairing social functions. Epidemiological data shows a lifetime prevalence of 3.4% and a 12-month prevalence of 2.1% for MDD in China, which are also growing. This disorder has a high recurrence rate, a high suicide rate, and a high disability rate, putting a serious burden to patients and their family members. For existing antidepressants, their response and remission rates are not satisfactory, and it’s common to see a slow onset of action, residual symptoms, a high recurrence risk, and multiple adverse reactions in patients taking them. Therefore, how to quickly and effectively control the symptoms of MDD and further improve the efficacy of antidepressants and patient prognosis is a challenge in developing such drugs today.
LY03021 acts on three targets: NET, DAT, and GABAAR. By targeting synaptic GABAA receptor (subtype α1β2γ2) and extrasynaptic GABAA receptor (subtype α4β3δ), this drug helps GABA activate GABAA receptors, regulates the glutamate/GABA balance in the brain, inhibits the excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis, and rapidly relieves depressive symptoms. At the same time, it also increases norepinephrine (NE) and dopamine (DA) levels in the brain by inhibiting NET and DAT, significantly improving core symptoms, anhedonia, and sexual dysfunction in MDD patients. Through the wake-promoting effects of NE and DA, it also eliminates adverse reactions such as sedation, drowsiness, and loss of consciousness caused by GABA receptor activation.
Non-clinical studies showed that LY03021 significantly inhibited depressive symptoms in animal models 24 hours after administration, and continuous administration could maintain the efficacy until the end of the 21-day study. Apart from its rapid onset of action and sustained efficacy in long-term, continuous administration, this drug also has a good safety profile, for its NOAEL (no-observed-adverse-effect-level) is 50 times above its effective dose.
Dr. Tian Jingwei, Executive Vice President of Luye Institute for Innovative Research at Luye Pharma Group, said: "The complex pathogenesis of MDD involves the interaction among multiple neurotransmitters in the brain. Regulating multiple targets through neural circuits in the brain is a novel strategy for developing antidepressants. By acting on NET, DAT, and GABAAR at the same time, a drug will be able to relieve depressive symptoms quickly. Such an MoA will help to improve the efficacy of antidepressants and reduce their adverse reactions to better address clinical needs. Working in the CNS (Central Nervous System) therapeutic area for over a decade, we have developed and launched a number of innovative products. Guided by an understanding of patients’ unmet needs, we are leveraging our CNS expertise to develop the next-generation drugs with a novel MoA. By doing this, we are contributing to the improvement of public health."
There is a huge demand for CNS drugs, including those for treating MDD. However, new drug development in this area has been relatively slow. Luye Pharma has developed a range of internationally competitive innovative drugs and formulations, making it a leader among Chinese pharmaceutical companies in this therapeutic area. Here are some examples: Erzofri® (paliperidone palmitate) extended-release injectable suspension and Rykindo® (risperidone) for extended-release injectable suspension, both have been approved for marketing in the U.S.; and Ruoxinlin® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets) and Jinyouping® (Rotigotine Microspheres for Injection), both have been launched in China. In addition, the company is also conducting clinical studies for several drugs filed through China’s Class 1 pathway, such as LY03020, a dual agonist targeting TAAR1/5-HT2CR, and LY03015, which targets VMAT2 and Sigma1.
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About Luye Pharma Group
Luye Pharma Group is an international pharmaceutical company dedicated to the R&D, manufacturing, and sale of innovative medications. The company has established R&D centers in China, the U.S. and Europe, with a robust pipeline of over 30 drug candidates in China and more than 10 drug candidates in other international markets. Luye Pharma maintains high-level international standards in novel drug delivery technologies including microspheres, liposomes, and transdermal drug delivery systems. The company has achieved multiple innovations in new chemical entities and antibodies, and is also actively making strategic developments in the fields of cell therapies and gene therapies.
Luye Pharma is developing a global supply chain of 8 manufacturing sites built up around the world, with GMP quality management and control systems established in line with international standards. With more than 30 products covering oncology, the central nervous system, cardiovascular, gastroenterology, metabolism and other therapeutic areas, business is conducted in over 80 countries and regions around the world, including the largest pharmaceutical markets -- China, the U.S., Europe, and Japan, as well as in fast growing emerging markets.
Shanghai, November 11, 2024 - Luye Pharma Group today announced that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has approved its Investigational New Drug (IND) application for LY03021 for the treatment of Major Depressive Disorder (MDD). LY03021 is designated as a Class 1 innovative drug in China.
LY03021 is an inhibitor of the norepinephrine transporter (NET) and the dopamine transporter (DAT) as well as a gamma-aminobutyric acid type A receptor-positive allosteric modulator (GABAAR PAM). Developed on Luye Pharma’s New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform, this investigational antidepressant works on the three targets above, a novel mechanism of action (MoA) that no other investigational drugs currently under development have been publicly reported to employ, making LY03021 a potential first-in-class drug.
MDD is a mood disorder characterized by significant and persistent depressive symptoms impairing social functions. Epidemiological data shows a lifetime prevalence of 3.4% and a 12-month prevalence of 2.1% for MDD in China, which are also growing. This disorder has a high recurrence rate, a high suicide rate, and a high disability rate, putting a serious burden to patients and their family members. For existing antidepressants, their response and remission rates are not satisfactory, and it’s common to see a slow onset of action, residual symptoms, a high recurrence risk, and multiple adverse reactions in patients taking them. Therefore, how to quickly and effectively control the symptoms of MDD and further improve the efficacy of antidepressants and patient prognosis is a challenge in developing such drugs today.
LY03021 acts on three targets: NET, DAT, and GABAAR. By targeting synaptic GABAA receptor (subtype α1β2γ2) and extrasynaptic GABAA receptor (subtype α4β3δ), this drug helps GABA activate GABAA receptors, regulates the glutamate/GABA balance in the brain, inhibits the excessive activation of the hypothalamic-pituitary-adrenal (HPA) axis, and rapidly relieves depressive symptoms. At the same time, it also increases norepinephrine (NE) and dopamine (DA) levels in the brain by inhibiting NET and DAT, significantly improving core symptoms, anhedonia, and sexual dysfunction in MDD patients. Through the wake-promoting effects of NE and DA, it also eliminates adverse reactions such as sedation, drowsiness, and loss of consciousness caused by GABA receptor activation.
Non-clinical studies showed that LY03021 significantly inhibited depressive symptoms in animal models 24 hours after administration, and continuous administration could maintain the efficacy until the end of the 21-day study. Apart from its rapid onset of action and sustained efficacy in long-term, continuous administration, this drug also has a good safety profile, for its NOAEL (no-observed-adverse-effect-level) is 50 times above its effective dose.
Dr. Tian Jingwei, Executive Vice President of Luye Institute for Innovative Research at Luye Pharma Group, said: "The complex pathogenesis of MDD involves the interaction among multiple neurotransmitters in the brain. Regulating multiple targets through neural circuits in the brain is a novel strategy for developing antidepressants. By acting on NET, DAT, and GABAAR at the same time, a drug will be able to relieve depressive symptoms quickly. Such an MoA will help to improve the efficacy of antidepressants and reduce their adverse reactions to better address clinical needs. Working in the CNS (Central Nervous System) therapeutic area for over a decade, we have developed and launched a number of innovative products. Guided by an understanding of patients’ unmet needs, we are leveraging our CNS expertise to develop the next-generation drugs with a novel MoA. By doing this, we are contributing to the improvement of public health."
There is a huge demand for CNS drugs, including those for treating MDD. However, new drug development in this area has been relatively slow. Luye Pharma has developed a range of internationally competitive innovative drugs and formulations, making it a leader among Chinese pharmaceutical companies in this therapeutic area. Here are some examples: Erzofri® (paliperidone palmitate) extended-release injectable suspension and Rykindo® (risperidone) for extended-release injectable suspension, both have been approved for marketing in the U.S.; and Ruoxinlin® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets) and Jinyouping® (Rotigotine Microspheres for Injection), both have been launched in China. In addition, the company is also conducting clinical studies for several drugs filed through China’s Class 1 pathway, such as LY03020, a dual agonist targeting TAAR1/5-HT2CR, and LY03015, which targets VMAT2 and Sigma1.
###
About Luye Pharma Group
Luye Pharma Group is an international pharmaceutical company dedicated to the R&D, manufacturing, and sale of innovative medications. The company has established R&D centers in China, the U.S. and Europe, with a robust pipeline of over 30 drug candidates in China and more than 10 drug candidates in other international markets. Luye Pharma maintains high-level international standards in novel drug delivery technologies including microspheres, liposomes, and transdermal drug delivery systems. The company has achieved multiple innovations in new chemical entities and antibodies, and is also actively making strategic developments in the fields of cell therapies and gene therapies.
Luye Pharma is developing a global supply chain of 8 manufacturing sites built up around the world, with GMP quality management and control systems established in line with international standards. With more than 30 products covering oncology, the central nervous system, cardiovascular, gastroenterology, metabolism and other therapeutic areas, business is conducted in over 80 countries and regions around the world, including the largest pharmaceutical markets -- China, the U.S., Europe, and Japan, as well as in fast growing emerging markets.
