PR93850

CHONGQING, China, Dec. 23, 2021 /PRNewswire=KYODO JBN/ --

- Showing a comprehensive antidepressant efficacy and a good safety profile

without an impact on sexual function

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 19th National 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 change of the total score on the Montgomery–Åsberg

Depression Rating Scale (MADRS) from the baseline and the change of the CGI-I

score after the 6-week treatment, displaying a 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, 80 mg, and 160 mg in terms of the

change of the CGI-S score, displaying a difference of statistical significance

(P<0.05); in addition, the response rate (the reduction of MADRS total score

from the baseline greater than or equal to 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 fewer than or equal to 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, 80 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 under study in 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 making

strategic developments in the fields of biological antibodies, cell therapies

and gene therapies, among others.

Luye Pharma is 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

SOURCE  Luye Pharma Group