Multiple myeloma drug Darzalex (daratumumab) will enter the clinical field next month after successfully expanding its coverage.

As new drugs such as bispecific antibody-based therapies are becoming the last treatment option in Korea, Darzalex’s success in expanding coverage has raised the prospect that combination therapy could emerge as the standard of care.

# According to industry sources on the 18th, the National Health Insurance Service and Janssen Korea recently completed drug pricing negotiations on the multiple myeloma drug Darzalex for its reimbursement extension.

Multiple myeloma is highly resistant and refractory to existing therapies and relapses frequently. Patients who have experienced triple-refractory multiple myeloma - those who have experienced three or more relapses or three or more failures to prior therapies - represent approximately 15% of all multiple myeloma patients and have a median life expectancy of only 5.1 months.

Therefore, it is important to treat multiple myeloma with a combination of clinically proven agents from the earliest stage of diagnosis. In the global market, combination therapies that use Darzalex are regarded as the standard of care for the initial treatment of multiple myeloma.

“Darzalex is used as a first-line treatment worldwide and is the first monoclonal antibody drug approved for the treatment of multiple myeloma,” said Dr. Chang-Ki Min, Professor of Hematology at St. Mary's Hospital in Seoul. ”Patients who are candidates for newer therapies such as CAR-T cell therapy and bispecific antibody therapy are those who have failed therapies using monoclonal antibodies such as Darzalex, proteasome inhibitors, and immunotherapies.”

The DVTd regimen (Darzalex+Bortezomib+Thalidomide+Dexamethasone) is a 4-drug regimen that adds Darzalex to the VTd regimen (Bortezomib+Thalidomide+Dexamethasone).

However, in Korea, Darzalex has been used only as a fourth-line monotherapy since it was approved for the treatment of relapsed or refractory multiple myeloma) that has received three prior therapies (fourth or later line).

Among them, Janssen Korea has been actively promoting the reimbursement extension of Darzalex since last year and recently agreed to negotiate the drug price with the National Health Insurance Service, which is the final step.

Following the conclusion of the drug price negotiations, the Health Insurance Review and Assessment Service has also started revising the anticancer drug reimbursement standards.

In other words, HIRA has decided to establish reimbursement standards for DVTd therapy for multiple myeloma patients who have not previously received chemotherapy.

HIRA explained that DVTd therapy is “mentioned in many textbooks, and is recommended as category 2A in the NCCN guidelines and as the new standard induction therapy in the ESMO guidelines ([I, A]). However, the ESMO guidelines state that there is no established standard of care for consolidation therapy.”

It added, “This regimen consists of 4 cycles (induction) and 2 cycles (consolidation) before and after hematopoietic stem cell transplantation, however, the consolidation therapy is not yet a standard of care in this disease, so the reimbursement standard is set only for the 4 cycles of induction therapy, considering how maintenance therapy is also reimbursed after transplantation, reducing the medical need for consolidation therapy.”

With the drug price negotiations settled and the HIRA’s reimbursement notice, it is likely that the reimbursement extension will take effect next month.

In the clinic, when the Darzalex-containing DVTd therapy is reimbursed as a first-line therapy, subsequent treatment strategies will also likely be quickly revised.

Bispecific antibodies and the  CAR-T therapy Kymriah will likely become more prominent as fourth-line options for multiple myeloma.

Bispecific antibody-based drugs include Janssen's Tecvayli (teclistamab), Talvey (talquetamab), and Pfizer's Elrexfio (elranatamab). These drugs have been approved and used in the field as the fourth-line therapy option for multiple myeloma in recent years.

At the same time, Janssen also has a CAR-T treatment, Carvykti (ciltacabtagene autoleucel), approved in Korea.

“Without Darzalex, the application of the latest therapies, such as CAR-T therapies and bispecific antibody drugs, may be delayed,” said a professor of Hematology at a tertiary hospital who requested anonymity. ”According to current standards, patients must first use Darzalex before receiving CAR-T cell therapy. This delays access to effective treatments.”

“If Darzalex’s reimbursement is successfully extended, the reimbursement challenges of bispecific antibody drugs will rise as a hot topic this year.”