13-year-old Choi was diagnosed at age 2 with the hard-to-treat epilepsy Lennox-Gastaut syndrome. After that, the medical cannabis-derived treatment Epidiolex from U.K.-based GW Pharmaceuticals was introduced in Korea. Although national health insurance coverage was possible, Choi's mother gave up. To receive reimbursed prescriptions, she would have to prove that at least five existing epilepsy drugs were ineffective. But the more drugs they tried, the more lethargic the child became, and side effects such as liver toxicity emerged. Choi's mother skipped the procedure to verify the effects of other drugs and, even though it costs a lot, continues to use Epidiolex privately without insurance because the child's seizures have clearly decreased after taking it.
38-year-old Kwon was diagnosed five years ago with tuberous sclerosis, a hereditary disorder that causes epilepsy symptoms. Seizures made daily life difficult, so Kwon could not even consider regular employment with the four major insurance protections and is getting by on minimal income. Hearing that Epidiolex could be imported into Korea raised hope, but because it is not covered by insurance, Kwon does not even dare seek a prescription. Kwon said they check clinical trial listings online every day hoping to participate in new drug trials, but finding patient recruitment is very difficult.
The Ministry of Food and Drug Safety approved Epidiolex in 2019 after the U.S. Food and Drug Administration's approval. Importation became possible only for treating patients with rare, hard-to-treat epilepsies such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis. But not many patients currently benefit from the drug because it is difficult to receive national health insurance benefits. Experts suggested loosening insurance and clinical trial regulations so more patients can benefit and to promote new drug development.
◇a monthly drug bill of 30 million won to pass the reimbursement threshold
Epidiolex costs more than 1.2 million won per bottle per dose, reaching 30 million won a month. To reduce patient burden, from 2021 national health insurance coverage cut the per-bottle cost to about 200,000 won, greatly reducing the burden.
But only a very small number of patients receive insurance benefits. The National Health Insurance Service designated only Dravet syndrome and Lennox-Gastaut syndrome among the three diseases for which Epidiolex was approved as reimbursable. Those two disorders account for less than 10% of all epilepsy patients. Many more tuberous sclerosis patients must still be treated without insurance coverage.
The process to receive reimbursed prescriptions is not simple. Patients must submit an application for patient import approval to the Ministry of Food and Drug Safety, along with a detailed medical certificate stating dosage and administration, medical records, and a physician's medical opinion that no alternative treatment exists. Only after approval can the drug be obtained through the Korea Center for Rare and Essential Drugs. It often takes months to get approval.
In particular, to qualify for reimbursement, patients must prove that despite using at least five of 11 existing epilepsy treatments, seizure frequency did not decrease by 50% or more. Patients and caregivers say it can take years just to try five strong drugs, and many children cannot endure the side effects during that process.
◇clinical research '0'…a blind spot in cannabis treatment development
That is not the only problem. Currently in Korea there are virtually no clinical trials of Epidiolex or similar treatments. Related studies are under way in the Gyeongbuk regulatory free zone, the Korea Institute of Science and Technology (KIST) and some university hospitals, but domestic narcotics control law blocks any clinical trials in which actual patients can participate. It is hard to find international joint clinical trials, let alone animal experiments.
By contrast, Japan conducted a phase 3 trial in 2019, the year after FDA approval, targeting Japanese patients. The clinical trials conducted earlier for FDA approval were limited to the United States, Canada, the United Kingdom, France, Australia and Israel, and Japan was the first in Asia to participate.
Like Korea, Japan allows the import of the drug only for some epilepsy patients. But once formal approval is obtained after clinical trials, most of the drug cost is covered by health insurance, greatly lowering costs and expanding the range of treatable conditions. Distribution procedures are also simplified, making it relatively easy for general hospitals to prescribe it. Given these circumstances, domestic patients and families say they would rather go abroad than wait in pain for the drug.
Kim Gwang-gi, professor of neurology at Dongguk University Ilsan Hospital and planning director of the Korean Epilepsy Society, said, "About 50,000 epilepsy patients in Korea live with the fear that they could suddenly collapse from a seizure anywhere and at any time," and added, "Current reimbursement standards are excessively narrow. It is urgent to expand indications and improve real accessibility to reduce the suffering of patients and families."
Eun Baek-rin, professor at Woori Children's Hospital pediatric neurodevelopment clinic and former director of Korea University Guro Hospital, also said, "Although Epidiolex has some side effects, it has proven to be quite effective for current hard-to-treat epilepsy patients in Korea," and advised, "Considering the state of national health insurance finances, a compromise is needed to expand benefits for patients who urgently need the drug."
Research has increasingly shown that medical cannabis may be effective for other brain disorders as well. Clinical studies to verify this are also under way. King's College London (KCL) has been conducting a clinical trial since 2020 to determine whether the cannabis component cannabidiol (CBD) is effective and safe at reducing hallucinations and delusions in Parkinson's disease patients.
Thailand is conducting a clinical trial evaluating the effects of CBD drugs in Parkinson's patients. The University of British Columbia (UBC) in Canada is running a clinical trial assessing CBD's effectiveness for depressive symptoms in bipolar disorder. Domestic researchers hope regulations will be relaxed so they can participate in joint clinical trials with foreign institutions.