[Contribution] A physician's regret over delayed introduction of cenobamate in Korea

Cenobamate is an anti-seizure drug developed by SK biopharmaceuticals, a Korean company. It won marketing authorization in the U.S. in November 2019 and Europe in March 2021, following global phase 2 and 3 clinical trials in patients with drug-resistent epilepsy. The exact number of patients in these studies is unclear, but more than 150 Korean patients with epilepsy seemed to have participated.

Even though it targets drug-resistent epilepsy patients, the drug will likely be a game changer and a breakthrough in the treatment of epilepsy due to its significant seizure control effect and high seizure-free rate. I have heard from some U.S. and European doctors that they feel it is a must-try for confirming drug-refractory epilepsy.

Reflecting this effect, cenobamate's U.S. sales grew 60.1 percent on-year to 270.8 billion won ($194.8 million) in 2023. In two years, its sales have tripled the 78.2 billion won in 2021. This notwithstanding, the reality is that cenobamate is still unavailable in Korea, except for some patients who participated in clinical trials.

Let me introduce some anti-seizure drugs for domestic use. Lacosamide, developed in Germany, was approved in the United States and Europe in 2008 and licensed in Korea in 2010. However, it was used without reimbursement because the company did not agree on the drug price due to the low level of reimbursement. So, it was used only in a tiny number of epilepsy patients because of the high drug price. It was eventually withdrawn from Korea. A generic by a Korean company won approval in 2016.

Perampanel, developed in Japan, was approved in the U.S. and Europe in 2012, and in Korea in 2015, and is being used after a price negotiation with the Health Insurance Review and Assessment Service (HIRA). Brivaracetam, developed in Belgium, was approved in the U.S. and Europe in 2016 and Korea in 2019. Still, it remains unavailable in Korea because the price bargaining has not been settled with HIRA. It will likely be available only as a generic in 2026 when the patent expires.

Diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray, which are used as rescue drugs for repeated seizures, are very useful in other countries. However, I understand that foreign companies do not even think of entering Korea due to this country’s low drug price policy. Understandably, the government is pursuing a low-price policy, considering the increasing healthcare costs and the pursuit of sound healthcare finances in Korea.

However, lowering drug prices unconditionally will increase  the exclusion of Korea when drugmakers launch products globally. This is not the way to go when the government's role is to promote the health of its citizens through quality care. It is essential to make the health insurance finances sound to increase drug prices and reduce cases where Korea is excluded in drug launching, but this issue is beyond the scope of my expertise.

Aside from the actual availability of the drug, foreign drugmakers apply for approval in Korea two to three years after getting nods in the U.S. and Europe, as mentioned earlier. However, SK biopharmaceuticals has not even applied for a new drug license from the Ministry of Food and Drug Safety (MFDS), although it won approvals in the U.S. and Europe in 2019 and 2021. SK biopharmaceuticals explains the delay in introducing cenobamate by saying, "We do not have the workforce or organization to launch it in Korea, including licensing and marketing."

It would be more honest to say that it is not profitable for the company to create an organization because the number of patients with epilepsy in Korea is relatively small. After all, SK biopharmaceuticals did it directly in the U.S., a large market. Even if this issue is considered, It could have been easily solved had the company transferred its marketing rights to a Korean company in advance. In any case, it's hard to take the company's explanation at face value.

Dong-A ST, which acquired the domestic sales rights to cenobamate in January of this year, intends to apply for a new drug license from the Ministry of Food and Drug Safety by mid-2025. However, even under optimal conditions, factoring in the MFDS review period, negotiations on drug pricing with HIRA, and implementation across individual hospitals, it will likely be more than seven years after its U.S. launch and six years after its European launch before Korean doctors can prescribe cenobamate to patients with epilepsy in Korea.

"There was no consideration of the domestic drug pricing system or the number of patients," SK biopharmaceuticals says, commenting on its delayed introduction in Korea. In the U.S., cenobamate costs about 50,000 won or more per day. In Europe, where SK biopharmaceuticals has licensed the drug to another company, the price varies by country, but it is reportedly lower than the U.S. price. On the other hand, the most expensive anti-seizure drug is currently around 3,500 won per day for high doses used as a stand-alone drug in Korea.

From the standpoint of a company that has spent a lot of money to develop a drug, if it is sold at a low price in Korea, it will inevitably affect the prices of the drug in other countries that are already available or will be introduced in the future. It may be unreasonable to expect only "compassion," "humanity," or "consideration" from profit-seeking companies to solve this problem. Must I understand it with utilitarian thinking that delaying the introduction of the drug may be more beneficial to the national interest by expanding corporate profits instead of benefitting a few patients? How sad!

However, no matter what the reason, Korean patients with epilepsy participated in the approval process, and no one will ever understand emotionally if a drug developed by a leading Korean company cannot be used in Korea. I have communicated with SK biopharmaceuticals and the Ministry of Health and Welfare for a long time through the Korean Epilepsy Society and the Korea Bureau for Epilepsy. However, for one reason or another, I have not received a positive response to the company's measures to introduce cenobamate swiftly, nor have I seen any active governmental mediation efforts.

The company claims that they don't have the staff or organization to handle the new drug application and that it must complete additional clinical trials while the government says that it has no authority to intervene because it is a private company. However, we have never seen a case where a drug approved in the U.S. and Europe is not approved in Korea. Nor is the latter the attitude of a government responsible for the health of its citizens.

From the company's point of view, the real reason for the delay in the introduction of cenobamate is the damage caused by the low drug price and the lack of heart for epilepsy patients in its home country (which can be seen in that the company delayed the transfer of the license in Korea to January 2024 instead of transferring the license as soon as it was approved in Europe). From the government's viewpoint, it is presumed that the government does not want to be accused of putting pressure on private companies for one drug.

I urge SK biopharmaceuticals and Dong-A ST to take quick action for the swift introduction of cenobamate, and the government to intervene quickly.