Luye Pharma Releases Top-Line Results from a Phase II Clinical Trial of Its New Antidepressant Ansofaxine Hydrochloride Extended-Release Tablets

CHONGQING,China,Dec. 23,2021 --Luye Pharma Group today released the encouraging top-line results from a Phase II clinical trial of its new antidepressant,Ansofaxine Hydrochloride Extended-Release Tablets (LY03005),at the 19thNational Psychiatry Conference of the Chinese Medical Association.

In general,LY03005 demonstrated a comprehensive antidepressant efficacy as well as a good safety profile and tolerance based on the initial results of the Phase II clinical trial. In particular,no significant adverse events were found related to sexual function or weight change,and no significant increase of somnolence was observed.

LY03005 is a New Chemical Entity (NCE) with a novel acting mechanism. It is a potential Serotonin-Norepinephrine-Dopamine Reuptake Inhibitor (SNDRI/TRI). The drug has completed Phase I to Phase III clinical trials and is currently in the New Drug Application (NDA) phase in China.

The top-line results released this time are from a multicenter,randomized,double-blind,placebo-controlled Phase II study designed to preliminarily evaluate the efficacy and safety of LY03005 in treating Major Depressive Disorder (MDD) and explore the optimal dosing. 260 MDD patients were enrolled in the study and randomly assigned to receive the treatment with LY03005 (at doses of 40 mg,80 mg,120 mg,and 160 mg) or a placebo for 6 weeks. The main findings are as follows:

LY03005 reached the primary endpoint,showing a good response rate and remission rate.

Primary endpoint results show that the change of the 17-item Hamilton Depression Rating Scale (HAM-D17) total score from the baseline displayed a difference of statistical significance (P<0.05) for all dosing groups of LY03005 compared with the placebo after the 6-week treatment.

For the secondary endpoints,LY03005 was superior to the placebo for all dosing groups in terms of both the changeof thetotal score onthe Montgomery–Åsberg Depression Rating Scale (MADRS) from the baseline and the changeofthe CGI-I score after the 6-week treatment,displayinga difference of statistical significance (P<0.05 and P<0.1 respectively); LY03005 was superior to the placebo for the dosing groups of 40 mg,and 160 mg in terms of the change of the CGI-S score,displaying a difference ofstatistical significance(P<0.05); in addition,the response rate (the reduction of MADRS total score from the baseline≥50%)of LY03005 based on MADRS for the 80 mg and 160 mg dosing groups was 68% and 71% respectively,and the remission rate (MADRS total score ≤12) of these two dosing groups based on MADRS was 60% and 56% respectively,also displaying a difference of statistical significance (P<0.1).

LY03005 showed potential for improving symptoms such as anxiety and cognitive disorders

For the secondary endpoints,LY03005 was superior to the placebo for the dosing groups of 40 mg,and 160 mg in terms of the total HAM-A score,the HAM-A Somatic Anxiety Factor score,and the HAM-D17 Anxiety/Somatization Factor score,displaying a difference of statistical significance (P<0.1). In addition,the HAM-A Psychic Anxiety Factor score and the HAM-D17 Cognitive Dysfunction Factor score demonstrated a trend of declining from the baseline for all dosing groups.

LY03005 showed a good safety profile and tolerance,with no significant adverse effects on sexual functioning,weight,or sleep

The safety data shows: 1) LY03005 demonstrated a good safety profile and tolerance,and most of the adverse events were mild or moderate with a short duration,seldom resulting in the termination of treatment; 2) there was no significant difference between LY03005 and the placebo in terms of the Arizona Sexual Experiences Scale (ASEX) score,and no sexual dysfunction as an adverse event was found in the study; 3) only three cases of weight change were determined to be related to or possibly related to the drug used in the study,and all of the three cases were mild or moderate,showing recovery at the end of treatment; 4) LY03005 was similar to the placebo in terms of the incidence of somnolence.

A complete recovery for patients is only possible when the drug used for treating them is safe and tolerable with a comprehensive antidepressant efficacy

"The clinical performance demonstrated by LY03005 shows that it helps to improve patients' depressive symptoms and functional impairments,leading to a full recovery," said Professor Zhang Hongyan from the Peking University Sixth Hospital,who was the principal investigator during the Phase II clinical trial of LY03005. "The good safety profile of the drug makes it easier for patients to receive a standard treatment throughout the course,to help them get back to normal faster."

The main clinical manifestations of depression include core symptoms such as a depressive mood and lack of energy as well as concomitant symptoms such as cognitive and sexual impairments. Many patients would see improvements of their core symptoms after receiving a treatment with antidepressants,but their remaining concomitant symptoms may still impair their social functioning or even lead to the relapse of depression. "The treatment of depression should try to completely eliminate all the symptoms,including affective,somatic and cognitive symptoms,and address the improvement of patients' quality of life and the recovery of their social functioning,so as to achieve a stable and complete recovery in its real sense," added Professor Zhang.

In addition,poor patient compliance is another important factor affecting the prognosis of depression. The safety and tolerance of a drug have a considerable bearing on patients' willingness to receive treatment with the drug. Quite a few patients discontinued treatment due to intolerance,and some of them even refused to receive treatment from the very beginning,with the outcomes being significantly compromised. Addressing common adverse reactions to a drug,such as sexual dysfunction,weight increase,cognitive impairment,sedation or fatigue,is the key to increasing treatment compliance1.

"Developed as a 5-HT/NE/DA TRI,LY03005 is designed to address the unmet needs of patients,including the impairment of social functioning and drug intolerance in long-term use," said Dr. Tian Jingwei,Vice President of Non-Clinical Research at Luye Pharma Group,who is also head of the LY03005 project team. "Based on various studies that have been completed,we've validated many clinical benefits of the drug to patients. In the future,we'll conduct more clinical trials to further unleash its therapeutic potential and help depressive patients get back to normal as soon as possible."

In addition to China,LY03005 is also undergoing NDA phase in the U.S.,and has completed Phase I clinical trials in Japan.

About Ansofaxine Hydrochloride Extended-Release Tablets (LY03005)

LY03005 is a Class 1 New Chemical Drug in China developed by Luye Pharma Group on its New Therapeutic Entity (NTE)/New Chemical Entity (NCE) platform for the treatment of Major Depressive Disorder (MDD). In vitro and ex vivo studies as well as in vivo brain microdialysis have validated that LY03005 is a Serotonin-Norepinephrine-Dopamine Reuptake Inhibitor (SNDRI/TRI).

LY03005 inhibits the reuptake of serotonin (5-HT),norepinephrine (NE) and dopamine (DA) by binding to the serotonin transporter (SERT),the norepinephrine transporter (NET),and the dopamine transporter (DAT). After oral administration,the drug and its metabolite O-desmethylvenlafaxine (ODV) will be selectively distributed in the hypothalamus with a similar concentration,to exhibit the activity of a SNDRI. A study of the acting mechanism of LY03005 has been published in the global academic journal Frontiers in Pharmacology.

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. Along with a number of new drugs and new formulations in the central nervous system and oncology therapeutic areas understudyin the U.S. Europe and Japan,Luye Pharma has reached high-level international standards in novel drug delivery technologies including microspheres,liposomes,and transdermal drug delivery systems,as well as actively makingstrategic developments in the fields of biological antibodies,cell therapies and gene therapies,among others.

Luye Pharmais developing a global supply chain of 8 manufacturing sites with over 30 production lines in total,establishing GMP quality management and international standard control systems. With more than 30 products covering the central nervous system,oncology,cardiovascular,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.

Reference:

1. Li L,Ma X,et al.The guideline of depression prevention and treatment in China. 2. Beijing: Chinese Medical Multimedia Press; 2015. 106-107