Rybrevant reimb delayed in Korea…treatment gap persists

Non-reimbursement burden persists amid delayed listing discussions

Targeted therapy development challenges… Limited treatment options due to

NSCLC drug ‘Rybrevant’

The gap in treatment access continues as discussions on health insurance reimbursement for ‘Rybrevant,’ a treatment for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, have been postponed again.

This mutation is known for its low response rate to conventional EGFR-targeted therapies and for the limited treatment options available. With virtually no alternatives to Rybrevant currently available, reimbursement delays continue to place a financial burden on patients.

According to industry sources on the 11th, the Drug Reimbursement Evaluation Committee of the Health Insurance Review and Assessment Service (HIRA) recently issued a redeliberation decision regarding the adequacy of reimbursement for Janssen’s NSCLC treatment, Rybrevant (amivantamab).

The DREC evaluated its use as monotherapy for patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease has progressed during or after platinum-based chemotherapy.

Although Rybrevant received regulatory approval in Korea in December 2022, it has yet to obtain reimbursement coverage.

In addition, the Cancer Drug Deliberation Committee meetings held in September last year and January this year failed to establish reimbursement criteria for several regimens, including ▲ first-line carboplatin + pemetrexed combination therapy for EGFR exon 20 insertion patients; ▲ first-line lazertinib combination therapy for EGFR exon 19 deletion or L858R mutation patients; and ▲ carboplatin + pemetrexed combination therapy following EGFR TKI treatment.

Setbacks in development of exon 20 insertion targeted therapies… Rybrevant remains the only option

EGFR exon 20 insertion mutations are structurally complex and heterogeneous compared to exon 19 deletions or L858R mutations, making drug development particularly challenging.

In fact, cases of failed drug development have continued in the global market as well.

Takeda’s oral targeted therapy Exkivity (mobocertinib) initially received conditional approval based on an objective response rate (ORR) of 28% in early trials, but was withdrawn after failing to demonstrate improvement in progression-free survival (PFS) in the confirmatory Phase III EXCLAIM-2 study.

Development of poziotinib was also halted due to efficacy falling short of expectations and toxicity issues.

Amid these challenges, Rybrevant has effectively become the only approved treatment option in this setting.

Rybrevant is a bispecific antibody targeting both EGFR and MET. It is designed to inhibit not only EGFR mutations but also MET-driven resistance pathways.

In clinical practice, MET-based resistance mechanisms are observed in approximately 10–15% of all patients. This patient group has a relatively poor prognosis, and Rybrevant is therefore considered to offer meaningful potential in terms of long-term survival.

Rybrevant shows efficacy as first-line combination therapy… patient burden remains

While reimbursement discussions for Rybrevant are delayed, clinical practice is increasingly focusing on the value of first-line combination therapy rather than monotherapy.

In the Phase III PAPILLON study, Rybrevant in combination with pemetrexed and carboplatin improved both PFS and ORR compared to chemotherapy. The trial included 308 previously untreated patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 mutations.

In this study, median PFS was approximately 11.4 months in the combination group versus 6.7 months in the chemotherapy group.

However, since current reimbursement discussions are focused on its use as second-line monotherapy, some observers note a gap between the pace of accumulating clinical evidence and policy application.

The continued lack of reimbursement imposes a significant financial burden on patients. Annual treatment costs for Rybrevant without reimbursement are estimated at around KRW 150 million.

In particular, since the drug is administered once a week during the first four weeks, the financial burden is concentrated in the early treatment phase. After this initial phase, the dosing schedule switches to every two weeks. However, it is reported that the pharmaceutical company is currently operating a partial cost-support program for the initial treatment phase, thereby reducing the actual financial burden on patients. Under this program, a portion of the drug cost is covered during the first four weeks, and a certain percentage of the cost is also covered during the subsequent maintenance therapy phase.

Industry observers suggest that Janssen is placing greater strategic emphasis on its use as a combination therapy, which is gaining traction in clinical practice, rather than focusing solely on its monotherapy reimbursement.

Rybrevant is currently being developed in combination with Leclaza to expand into first-line treatment of EGFR-mutant NSCLC, while also broadening the potential for its use in the early treatment stages for Exon 20 insertion mutations.

However, while treatment strategies in clinical settings are shifting toward first-line combination therapy, reimbursement discussions remain stuck at second-line monotherapy, highlighting an ongoing disconnect between policy and clinical practice.