LUYE PHARMA GROUP LTD.
November 29, 2022, Shanghai - Luye Pharma Group announced today that the first patient has been dosed in a Phase II clinical study for its investigational drug LY03014, designated as a "New Class 1 Drug" in China. LY03014 is a small-molecule Gi protein-biased agonist of the mu-opioid receptor (MOR), which is intended to be used for the treatment of moderate-to-severe acute postoperative pain and breakthrough cancer pain. The Phase II clinical trial was a multicenter, randomized, double-blind, placebo-controlled, and parallel-group study. It was designed to evaluate the preliminary efficacy and safety of LY03014 as an analgesic in patients with moderate-to-severe pain after an abdominal surgery.
Opioids are the most commonly used medications for moderate-to-severe acute postoperative pain and breakthrough cancer pain. On the one hand, opioids can significantly improve the quality of life for patients with moderate-to-severe pain, and they are administered for no more than 72 hours after an operation, so there's no addiction concern. On the other hand, opioid-induced respiratory depression (OIRD) is a major cause of death. Therefore, all opioids available in the market have a black box warning. Furthermore, fatal respiratory depression is also the principal risk factor in using opioids currently available to manage postoperative pain and breakthrough cancer pain.
As a novel analgesic, LY03014 can separate respiratory depression and analgesia, and is expected to meet the unmet clinical needs above. The results of its Phase I clinical trials show that a single intravenous infusion of LY03014 significantly improved the pain tolerance of the subjects with an overall good safety profile. Non-clinical studies show that LY03014 has good blood-brain barrier permeability and a good pharmacokinetic profile. A proof-of-concept (POC) study shows that, in comparison with conventional MOR agonists, LY03014 can completely separate the Gi pathway and the β-arrestin-2 pathway, which mainly mediates adverse effects associated with MOR activation, such as respiratory depression, constipation, and opioid tolerance. The POC study also shows that, at equianalgesic doses, LY03014 was less likely to cause respiratory depression, gastrointestinal dysfunction or opioid tolerance in comparison with morphine. Another promising property of LY03014 observed in those studies is that, unlike other MOR agonists, it did not cause QTc prolongation, which can cause potentially fatal arrhythmias and liver toxicity. The research results were published in the European Journal of Medicinal Chemistry.
Globally, there are approximately more than 300 million patients receiving surgeries each year. More than 80% of them suffer from postoperative pain, of which about 75% is acute postoperative pain1. In China, approximately 4.57 million new cancer cases were reported in 20202. For cancer patients, pain is one of the most common and most unbearable symptoms. The incidence of pain is about 25% in newly diagnosed cancer patients and 60-80% in patients with advanced cancer, of which 1/3 have severe pain3.
According to data from IQVIA CHPA, the sales of anesthetics and analgesics in China were RMB 38.8 billion in 2021, with a compound annual growth rate (CAGR) of 13.6% from 2017 to 2021. Specifically, the sales of opioids in 2021 were RMB 18.1 billion, with a CAGR of 16.6% from 2017 to 2021. The sales growth of opioids outpaced that of the entire market for anesthetics and analgesics.
LY03014 is an innovative analgesic developed by Luye Pharma on its New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform. Ruoxinlin® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets), China's first Class 1 innovative drug for the treatment of Major Depression Disorder, was recently approved for marketing on this innovative platform, which is built with many years of dedicated efforts. The development of other investigational drugs is also taking place at an accelerated pace on this platform, including LY03015, a VMAT2 inhibitor for treating central nervous system diseases, and LY03012, an investigational analgesic. These products will enrich the company's portfolio and demonstrate the company's strength in this field, providing new options of high-quality treatments for patients.
References：
Opioids are the most commonly used medications for moderate-to-severe acute postoperative pain and breakthrough cancer pain. On the one hand, opioids can significantly improve the quality of life for patients with moderate-to-severe pain, and they are administered for no more than 72 hours after an operation, so there's no addiction concern. On the other hand, opioid-induced respiratory depression (OIRD) is a major cause of death. Therefore, all opioids available in the market have a black box warning. Furthermore, fatal respiratory depression is also the principal risk factor in using opioids currently available to manage postoperative pain and breakthrough cancer pain.
As a novel analgesic, LY03014 can separate respiratory depression and analgesia, and is expected to meet the unmet clinical needs above. The results of its Phase I clinical trials show that a single intravenous infusion of LY03014 significantly improved the pain tolerance of the subjects with an overall good safety profile. Non-clinical studies show that LY03014 has good blood-brain barrier permeability and a good pharmacokinetic profile. A proof-of-concept (POC) study shows that, in comparison with conventional MOR agonists, LY03014 can completely separate the Gi pathway and the β-arrestin-2 pathway, which mainly mediates adverse effects associated with MOR activation, such as respiratory depression, constipation, and opioid tolerance. The POC study also shows that, at equianalgesic doses, LY03014 was less likely to cause respiratory depression, gastrointestinal dysfunction or opioid tolerance in comparison with morphine. Another promising property of LY03014 observed in those studies is that, unlike other MOR agonists, it did not cause QTc prolongation, which can cause potentially fatal arrhythmias and liver toxicity. The research results were published in the European Journal of Medicinal Chemistry.
Globally, there are approximately more than 300 million patients receiving surgeries each year. More than 80% of them suffer from postoperative pain, of which about 75% is acute postoperative pain1. In China, approximately 4.57 million new cancer cases were reported in 20202. For cancer patients, pain is one of the most common and most unbearable symptoms. The incidence of pain is about 25% in newly diagnosed cancer patients and 60-80% in patients with advanced cancer, of which 1/3 have severe pain3.
According to data from IQVIA CHPA, the sales of anesthetics and analgesics in China were RMB 38.8 billion in 2021, with a compound annual growth rate (CAGR) of 13.6% from 2017 to 2021. Specifically, the sales of opioids in 2021 were RMB 18.1 billion, with a CAGR of 16.6% from 2017 to 2021. The sales growth of opioids outpaced that of the entire market for anesthetics and analgesics.
LY03014 is an innovative analgesic developed by Luye Pharma on its New Chemical Entity/New Therapeutic Entity (NCE/NTE) platform. Ruoxinlin® (Toludesvenlafaxine Hydrochloride Extended-Release Tablets), China's first Class 1 innovative drug for the treatment of Major Depression Disorder, was recently approved for marketing on this innovative platform, which is built with many years of dedicated efforts. The development of other investigational drugs is also taking place at an accelerated pace on this platform, including LY03015, a VMAT2 inhibitor for treating central nervous system diseases, and LY03012, an investigational analgesic. These products will enrich the company's portfolio and demonstrate the company's strength in this field, providing new options of high-quality treatments for patients.
References：
- Jeffrey L Apfelbaum1, Connie Chen etal. Postoperative Pain Experience: Results from a National Survey Suggest Postoperative Pain Continues to Be Undermanaged[J]. Anesth Analg, 2003(97):534 -40.
- International Agency for Research on Cancer - Cancer Fact Sheets - China. Available at https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf Accessed in November 2022.
- Diagnosis and Treatment Standards for Cancer Pain (2018 ed.):1
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Luye Pharma Group Ltd. published this content on 29 November 2022 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 30 November 2022 09:23:26 UTC.
