With the misuse and abuse of narcotic painkillers emerging as a social problem in Korea, there is a lot of attention on whether non-narcotic painkillers can be a solution.

Narcotic analgesics suppress pain transmission to the central nervous system for patients who see little efficacy when taking acetaminophen-type antipyretic analgesics or non-steroidal anti-inflammatory drugs (NSAIDs).

In Korea, various opioid drugs, such as morphine, fentanyl, codeine, oxycodone, and tramadol, are mainly used as narcotic analgesics.

While opioid analgesics are effective in reducing pain, they could cause constipation and vomiting and increase drug dependence, which can lead to addiction.

Notably, the use of fentanyl, which is made by refining and processing opium, is rapidly increasing.

According to the Ministry of Food and Drug Safety's data on the prescription status of narcotic analgesics used in the medical field for the past five years, fentanyl use increased from 891,434 cases in 2018 to 1,488,325 cases in 2020, a 67 percent jump over three years.

Fentanyl use in teenagers and young adults is also picking up as fentanyl-based pain relievers are easy to receive a prescription for and are also available in the form of patches. 

While there were only 44,105 cases in 2019, the number shot up to 61,087 in 2021.

This means that Korea is no longer safe from narcotic misuse, and the need for non-narcotic painkillers is emerging.

Korean pharmaceutical active in developing non-narcotic painkillers

Expectations are growing for Korean pharmaceutical companies to develop a non-narcotic painkiller with positive results in clinical trials.

Korean companies working on non-narcotic painkillers include Vivozon Pharmaceutical, Olipass, Mediforum, and iN Therapeutics.

Vivozon Pharmaceutical, which is ahead of the development process, recently confirmed the safety and efficacy of its non-narcotic painkiller, Unafra (ingredient: opiranserine), in phase 3 clinical trials in Korea.

Opiranserine is an investigational non-narcotic injection-type painkiller that effectively relieves moderate or severe pain. It is intended to be used as a first-line therapy for postoperative pain.

By simultaneously suppressing the serotonin receptor type 2A and glycine transporter type 2, which transmit pain signals, the multi-target inhibition of these signals in the central and peripheral nervous systems has increased analgesic efficacy and safety, Vivozon said.

In phase 3 clinical trials, the time-weighted summed pain intensity difference to baseline over 12 hours (SPID 12) was the primary endpoint to evaluate the analgesic effect of the VVZ-149 injection. Accordingly, the VVZ-149 group showed an average 35 percent higher pain reduction compared to the placebo group, and a statistically significant difference was confirmed with a p-value of 0.0047.

Based on the results of phase 3 clinical trial, the company plans to submit a new drug application (NDA) in Korea within the first half of this year.

Olipass recently disclosed the interim evaluation of a phase 2a clinical trial for OLP-1002, a new non-narcotic analgesic drug.

The interim results included data on 30 patients who completed the phase 2a study evaluation.

As a result of clinical trials, the OLP-1002 2μg administration group failed to secure statistical significance compared to the placebo group due to a slight difference in the key pain evaluation index.

However, in the 2 μg dose group, the analgesic efficacy reached its maximum in the fifth and sixth weeks of administration, and the analgesic effect was superior to that of the 1 μg dose group and the placebo group.

Mediforum is developing a natural product-based non-narcotic pain treatment.

Last year, the company signed a memorandum of understanding (MOU) with LSK Global PS for the phase 2 clinical trial and joint research and development of MF018, a non-narcotic candidate using natural products.

While the company had received approval for a phase 2 clinical trial from the Ministry of Food and Drug Safety in January 2020, it had been postponing the trial due to the spread of Covid-19.

iN Therapeutics, a subsidiary of Daewoong Pharmaceutical, announced the interim results of phase 1 clinical trials in Australia of iN1011-N17, a new drug candidate for non-narcotic osteoarthritis pain treatment, at the International Osteoarthritis Society (OARSI) held in Berlin, Germany in March last year.

According to the company, in preclinical trials, iN1011-N17 has proven efficacy superior to Nsaids-type pain relievers or tramadol, a narcotic pain reliever.

By conducting a phase 1 clinical trial, iN Therapeutics plans to secure important drug exposure data that can determine usage in future clinical trials, and confirm the safety, tolerability, and pharmacokinetic excellence of iN1011-N17.

Lawmakers raise concerns about poor fentanyl management 

During the 2022 parliamentary audit, the ruling and opposition parties brought up the issue of poor narcotic drug management.

With the problem of poor narcotic painkiller management reported to be serious, some lawmakers argued that punishment and regulation on medical institutions should be strengthened as a solution to the problem.

Notably, lawmakers suggested regulations that make it mandatory for medical institutions to review other medical institutions' prescription records during treatment, or to make it mandatory to install CCTVs or unmanned security devices to prevent theft or loss of narcotic drugs.

Such suggestions have already led to Rep. Kang Sun-woo of the Democratic Party and 10 other lawmakers proposing a revision bill to obligate physicians to check the patient's history of receiving narcotics for medical uses.

The bill aims to impose penalties on doctors who fail to comply with a revised Narcotics Control Act.

Regarding such talks and bills, the medical community stated that it clearly agrees that prescriptions and management must be done more carefully to prevent misuse and abuse of drugs.

However, a group of doctors working in Seoul said preparing a new basis for punishment was inappropriate, such as installing CCTVs to check the medication history and strengthening regulations. 

"Punishment provisions for misuse and abuse of narcotics already exist through numerous related laws, such as the Medical Act, the Pharmaceutical Affairs Act, and the Narcotics Control Act," Seoul Medical Association Policy Director Ja Hoon-jung was quoted by Doc News, a Korean medical news outlet, as saying. "Reinforcement of punishment or regulation is excessive and redundant legislation, and it will be difficult to expect actual improvement through such revisions."