Safer painkillers than morphine are on the market and licensed by NW Pharmaceuticals.

The new drug, Oliceridine (the product is called Olinvo®), was developed by Trevena and approved by the FDA on August 7, 2020 for the treatment of moderate and severe acute pain.
the drug was awarded fast-track treatment for moderate to severe acute pain by the FDA in 2015 and a breakthrough therapy for controlling moderate to severe acute pain in 2016.
May 2018, Trevena authorized the development and sale of Olceridine in China by Jiangsu Enhua Pharmaceutical Co., Ltd.
April 1, 2020, the drug IND was approved by the National Drug Administration (NMPA) for the chemical category, and in June 2020 obtained clinically implied permission to treat moderate to severe acute pain.
Figure 1. Oliceridine structural Oliceridine injections are selective opioid-subject agonists that activate only the G-path without affecting the beta-arrestin path.
the role of the beta-arrestin pathrapy is thought to be associated with adverse opioid-related reactions such as constipation, respiratory failure and tolerance.
opioids are the main drugs used to treat moderate and severe pain, and are also the gold standard for postoperative analgesms.
opioids have three subsumes, gene knock-out shows that the opioids are responsible for pain relief, but it is also the cause of respiratory suppression, gastrointestinal function, addiction and other adverse reactions.
studies have shown that there is a stimulating signaling path, in which pain is called by activating the G path, while constipation, respiratory suppression, and addiction are more regulated by the downstream beta-arrestin path.
key clinical studies The drug's approval is based on two Phase III clinical trials and a real-world study.
1. Phase III clinical trial APOLLO-1 APOLLO-1 (NCT02815709) in acute pain in hard tissue (cystic excision) was a Phase III, double-blind, randomized controlled trial for patients with moderate and severe pain after cystic excision, with a total of 389 patients receiving medication.
all olicridine dose groups (0.1 mg, 0.35 mg and 0.5 mg) were rapidly relieved of moderate to severe acute postoperative pain, with analgesic rates of 50%, 62% and 65.8%, respectively, and analgesic rates of 0.35 mg and 0.5 mg dose groups comparable to those in the morphine group (4 mg).
compared to morphine, it has good safety and tolerance for respiratory and gastrointestinal adverse reactions.
2. Phase III key clinical trial APOLLO-2 APOLLO-2 (NCT02820324) in acute pain in soft tissue (abdominal wall forming) was a randomized, controlled Phase III trial of acute pain after abdominal forming, in which 401 patients were treated with medication.
effective analgesic effects were observed in all three dose options (0.1 mg, 0.35 mg and 0.5 mg), with analgesic rates of 61.0%, 76.3% and 70.0%, respectively, of which 0.35 mg and 0.5 mg doses of olicridine showed the same effect as morphine.
treatment response rate of 0.35 mg and 0.5 mg was significantly higher in 10-15 minutes than in the morphine group.
3. Phase III Real-World Safety Study ATHENA ATHENA study is a Phase III, multi-center, open study that assessed the safety of olicridine in 768 patients with severe acute pain.
was conducted at 41 research centers in the United States.
patients with acute pain after surgery accounted for the majority (94%) of the study population, the most common types of surgery were orthopaedics (30%), colorectal (15%) and gynecology (15%).
results showed that adverse events were mostly mild or moderate.
most common adverse reactions are nausea, vomiting and constipation.
results show that the treatment of acute pain in oliceridine is generally safe and well-to-bear under a variety of surgical and medical conditions.
, oliceridine's performance was consistent among the group of patients studied, including older and obese patients, who were more likely to develop opioid-related adverse reactions.
Black Box Warning: Olinvo® has serious adverse reactions such as addiction, abuse, respiratory suppression, neonatal opioid withdrawal syndrome, and the risk of being associated with benzodiazepines or other central nervous system inhibitors.
, unlike other opioids used for intravenous administration, the maximum recommended daily dose ® 27 milligrams for Olinvo.
treatment of postoperative pain Intravenous opioids is an important treatment option for millions of hospital patients, with an estimated 45 million patients receiving them each year.
opioids are considered an important part of a patient's pain management program for operations that are expected to cause severe, long-term, or deep/visceral pain.
more and more complex and painful operations, which are increasingly burdening the hospital system.
, however, intravenous morphine and other drugs have limitations, including adverse reactions such as nausea, vomiting and respiratory suppression, which have a negative impact on the patient's recovery.
are still clinically necessary for an effective and well-mmune intravenous analgesic, especially for those who are more susceptible to these dose-limiting adverse reactions, such as the elderly, obese or impaired kidney function.
current hospital trends suggest that the number of these high-risk patients is growing.
clinical studies have shown that Oliceridine peaks in pain faster than morphine, and that Olicridine causes less risk of gastrointestinal dysfunction and respiratory suppression at the equivalent analgesic dose than morphine.
According to the Pharmacy Database, as of the time of release, there are 96 drugs for postoperative pain worldwide, of which 33 have been approved for sale, 27 are under development, and 28 have been withdrawn and terminated.
target competition pattern According to the Drug Crossing database, a search of target MOR1 showed 97 data results, with these drugs mainly focused on the treatment of pain and divine diseases.
Figure 2 Global MOR1 Targeted Drug Adaptation Distribution, Pictured from The Drug Crossing Database, as of August 2020 Figure 3 Global MOR1 Targeted Drug Research and Development Progress, Picture from the Drug Crossing Database, As of August 2020 Figure 4 Global MOR1 Targeted Drug Type Distribution, Picture from the Drug Crossing Database, as of August 2020 Figure 5 Global MOR1 Targeted Drugs Distribution of research and development companies, pictured from the Pharmaceutical Database, as of August 2020, there are 10 MOR1 targeted drugs for postoperative pain treatment, Morphine-6-glucuronide (morphine-6-glucosideide) is in the first echelon of research and development, is china's only MOR1 targeted drugs in the study, belongs to China's class 1 new drugs.
arginine ibuprofen/hydrochloric acid quemado is a compound consisting of cyclooxidase inhibitors (arginine ibuprofen) and opiate-subjected astrogens (hydrochloric acid curmador) for the treatment of tooth and postoperative pain.
developed by Farmalider and is currently in Clinical Phase III.
also used in postoperative analgesics are morphine-6-glucosides, an active metabolite of morphine in the body, belonging to opioid analgesics, targeting MOR1.
compared with morphine preparations, morphine-6-glucosides injection analgesic activity is stronger, longer maintenance time, better tolerance, can effectively improve nausea, vomiting, respiratory suppression and other adverse reactions.
the compound was originally developed by CeNeS Pharmaceuticals (development code CEE-04410), which was acquired by PAION in 2008.
2014, the drug's research and development rights in China were granted to Yichang People's Fu Pharmaceuticals.
, however, in China, Jiangsu Hengrui Pharmaceuticals (research and development code M6G) is also undergoing clinical Phase I trials.
, China's current systemic and local narcotic drug market size of about 5 billion yuan, narcotic drug market size of about 2 billion yuan.
china's per capita consumption of narcotic drugs is 1/10 of that of developed countries, medical morphine consumption accounted for 2% of the world, compared with other countries compared to the level of that drug disparity.
the past five years, the compound growth rate of hemp essence drugs in China is 28.5%, higher than the average growth rate of the pharmaceutical industry, highlighting that there is a huge clinical demand has not been met.
but the market for addictive and adverse reactions, such as morphine, fentany and duodenine, has shrunk year by year.
Therefore, the development of single-targeted, high safety, treatment window wider anaesthetic analgesic varieties in line with domestic and foreign research and development and clinical application trends, for the increasing number of surgical patients to provide better compliance drugs, to provide doctors with more choices.
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