Darzalex’s reimbursement has been in limbo for 3 years. Will it be different this time?

Attention is drawn to whether the reimbursement criteria for the multiple myeloma drug Darzalex (daratumumab), unchanged since May 2021, will be expanded for the first time in three years.

Proposals to expand the reimbursement standard for the DVd (daratumumab/bortezomib/dexamethasone) and DKd (daratumumab/carfilzomib/dexamethasone) three-drug regimens used to treat relapsed or refractory multiple myeloma passed the first and third meeting of the Cancer Disease Review Committee (CDRC) held by the Health Insurance Review and Assessment Service (HIRA) in February and April, respectively.

The DVd therapy won insurance benefits on the condition that Vd (bortezomib/dexamethasone) was fully reimbursed (5 percent out of 100), and Darzalex was fully paid (100 percent) by the patient in May 2021. The proposal to switch the entire DVd regimen to full reimbursement (5 percent out of 100) was passed at the first meeting this year.

The DKd regimen, which was tabled at the third meeting, has a more complicated background. That’s because the indication for the second-generation proteasome inhibitor (PI) Kyprolis (carfilzomib), which is included in the DKd regimen, is not included in Darzalex's domestic approval.

While the combination with bortezomib (DVd), a first-generation PI, is included in Darzalex's indication based on clinical studies led by Janssen, the later combination with Kyprolis (DKd) was led by Amgen and is only registered in the Kyprolis’ approval.

As a result, reimbursement for the DKd regimen has been through a rough patch. It was a combination of the two original drugs, which still are not off-patent, and the different manufacturers of the two drugs have made it virtually impossible to get together to discuss reimbursement.

Amgen filed a reimbursement application after the DKd's approval in May 2021, which was discussed in November 2022 but was rejected, and the application was also rejected in March 2023.

Notably, the March 2023 application was led by the Korean Society of Hematology, not the pharmaceutical company.

At the time, Janssen was applying for full reimbursement of the DVd regimen, and the society, which was aware of such an application, requested that the reimbursement of DKd and DRd (daratumumab/lenalidomide/dexamethasone) be reviewed at the same time as DVd.

The society's position was that these three three-drug regimens, which are used at the same level to treat relapsed or refractory multiple myeloma, have different patient populations with different needs and that separate reimbursement could lead to confusion at the point of care. However, CDRC did not accept the proposal.

Finally, Janssen and Amgen applied for reimbursement under their respective indications, and DVd and DKd therapies have passed through the first reimbursement gate.

The DKd regimen was approved by adding Darzalex to the previously covered Kd regimen (5/100) on the condition of full patient co-payment (100/100).

However, it is unclear whether the drug price negotiation with the Pharmaceutical Reimbursement Evaluation Committee (PREC) and the National Health Insurance Service (NHIS) will go smoothly in the case of DKd therapy.

The addition of Darzalex to the existing Kd regimen would significantly increase the duration of use of Kyprolis and Darzalex, necessitating a price adjustment. This would require both Amgen and Janssen to negotiate the price of the DKd regimen.

According to the Phase 3 CANDOR study, the approved trial of the DKd regimen, the median progression-free survival (mPFS) of patients treated with DKd was 28.4 months, compared to 15.2 months in the control Kd regimen. Thus, the addition of Darzalex to the Kd regimen extended the duration of treatment by more than a year.

The good news is that Janssen is negotiating with the government for the same period with the DVd regimen, so there is an opportunity to discuss the impact of Darzalex’s drug price resulting from DKd’s reimbursement.

Against this backdrop, patients and medical professionals are paying keen attention to whether the reimbursement expansion of Darzalex will become a reality, as they have aspired to over the past three years.