“The hospital was supposed to collect T cells on Wednesday, but my boy’s condition worsened in the early morning that day. After holding out for a day and a half next to mom and dad, he passed away on Thursday on June 10, 2:53 p.m. I’ll regret not being able to give CAR-T cell (chimeric antigen receptor T-cell) therapy for the rest of my life. Still, I comfort myself thinking he went to a place where he isn’t sick anymore. I hope CAR-T cell therapy could be accessible as soon as possible so there will be no child like mine who lost life waiting for it.”

So wrote the mother of a 13-year-old boy, who died just before T-cell collection for CAR-T cell therapy, on her blog on June 11.

The boy was diagnosed with acute lymphocytic leukemia in 2014 and had been fighting the disease for seven years. Kymriah, Novartis’ new CAR-T cell treatment, recently arrived in Korea, and he waited for an opportunity to benefit from its excellent effect on blood cancers.

However, the boy couldn’t get it in the end.

Not only the boy but many other Korean blood cancer patients have failed to get CAR-T cell therapy. Four years have passed since Kymriah won the FDA’s approval to treat acute lymphoblastic leukemia in August 2017, but the drug was administered to the first Korean patient in June this year.

The development of CAR-T cell therapy is considered the greatest achievement in blood cancer treatment. In addition, CAR-T cell therapy is called a “dream treatment” for patients who do not have any treatment options due to repeated relapses.

Health experts predict that CAR-T cell therapy will eventually become the standard treatment for blood cancer.

‘Late introduction of CAR-T cell therapy, Korea’s painful mistake’

Why did it take so long for Korea to introduce CAR-T cell therapy?

Lee Je-hwan, president of the Korean Society of Hematology, attributed the blunder to the exclusion of Korean patients from early clinical trials.

“As CAR-T cell therapy requires complicated manufacturing processes, strict regulation, and high costs, Korean patients could not participate in early clinical trials provided by multinational drugmakers,” Lee said. “That is why Korea was late to introduce the treatment.”

Lee Je-hwan, president of the Korean Society of Hematology, said Korean researchers should develop a homegrown CAR-T therapy to lower costs.
Lee Je-hwan, president of the Korean Society of Hematology, said Korean researchers should develop a homegrown CAR-T therapy to lower costs.

However, as regulations related to the Advanced Regenerative Medicine Act became clearer and Kymriah won the nod from the Ministry of Food and Drug Safety, local CAR-T cell therapy will gain momentum, Lee predicted.

“After the advanced medicine act was legislated, many research institutions received greenlight as regenerative medicine labs, and clinical trials of CAR-T cell therapy have begun in Korea,” he said. “Also, research funds will be generated to speed up the development of homegrown CAR-T cell therapy.”

Curocell, a local biotech firm, has begun a phase-1 study of CRC01, a CAR-T cell therapy candidate. On April 20, a local patient received the first CAR-T cell therapy candidate at Samsung Medical Center (SMC).

The investigational drug for the treatment of relapsed and refractory diffuse large B-cell lymphoma (DLBCL) will be tested on 100 patients through a phase-2 trial at SMC, the only medical institution in Korea that received the permit for “human cell management business.”

With domestic research getting more active, Korean patients will have better access to CAR-T cell therapy, Lee explained.

“The most difficult problem in getting CAR-T cell therapy is money,” he said. “Kymriah alone costs 400 million won ($353,874) to 500 million won, and if we consider the cost of pre-treatment and post-treatment, it costs well over 500 million won.”

For Korean patients to get CAR-T cell therapy, it has become reimbursable.

However, if the government has to cover 400 million won to 500 million won cost, it will find it hard to earn social consensus, Lee added.

Kymriah requires extra treatment, which raises the cost of the entire treatment, Lee went on to say. “For example, after CAR-T treatment, the patient needs drugs such as tocilizumab to manage cytokine release syndrome (CRS). But there is no preparation for reimbursement for this drug,” he said.

Therefore, Korean researchers should develop a homegrown CAR-T therapy, he emphasized. “China is developing its therapy. If Korea can manufacture a local CAR-T cell therapy, we could find a solution to the money problem,” he added.

CAR-T cell therapy delayed due to insufficient permissions for human cell management business

The loophole in the advanced medicine act is cited as part of the reasons for the delayed use of CAR-T cell therapy in Korea.

Not only Curocell but Janssen is conducting a phase-3 study of investigational CAR-T cell therapy in Korea. The study is testing the candidate JNJ-68284528 to treat multiple myeloma in 12 Korean patients at SMC, Seoul St. Mary’s Hospital, and the Seoul National University Hospital.

However, SMC is the only hospital that obtained the license for the human cell management business. So, patients at the other institutions should wait for the hospital to get the permit.

“To use CAR-T cell therapy, the hospital has to have the permit for human cell management business,” Lee said. In addition, as Kymriah requires the hospital’s collection and separation of T cells, the hospital has to have the license, he added.

The boy mentioned earlier had to move to SMC after finding out that the previous hospital he used to go to for seven years was waiting to get the human cell management business permit in August.

Although it was belated, CAR-T cell therapy is gradually becoming possible in Korea. As Kymriah became the first drug to receive approval based on the Advanced Regenerative Medicine Act, health officials have started to discuss granting insurance benefits to Kymriah.

However, several years have already passed since patients first heard that CAR-T cell therapy could be a cure.

Industry watchers are paying attention to whether the treatment could become accessible to Korean patients swiftly.

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