Janssen's Rybrevant makes 3rd attempt for reimbursement. Will it succeed?

Janssen's Rybrevant (amivantamab), a treatment for EGFR exon20 insertion non-small cell lung cancer (NSCLC), a rare form of lung cancer with a poor prognosis, is making its third attempt to get reimbursement in Korea.

The drug’s third challenge for insurance coverage comes when the “nominality” of the government’s fast-track approval system comes under scrutiny once again, as many rare lung cancers targeted therapies that won regulatory approval based on only phase 2 clinical trial results have failed to receive insurance coverage for over two years.

According to industry insiders, Rybrevant will likely be tabled on the Health Insurance Review and Assessment Service (HIRA)’s third Cancer Disease Review Committee (CDRC) this year, which is scheduled for next Wednesday for its third review.

The Yoon Suk Yeol administration has advocated improved access to treatment by strengthening the coverage of drugs that treat severe diseases as a national priority. However, no rare lung cancer drugs that were quickly approved in recognition of clinical demand have been listed on the reimbursement list so far.

For instance, RET-targeting anticancer drugs Gavreto (pralsetinib) and Retevmo (selpercatinib), which were approved in March 2022, remain non-reimbursed, as do the MET exon 14 deletion mutation-targeting drugs Tabrecta (capmatinib) and Tepmetko (tepotinib), which were approved in November 2021.

All have knocked on the reimbursement door at least once, but none have reached the coverage sphere more than two years after approval.

Rybrevant, which won approval from the Ministry of Food and Drug Safety (MFDS) in February 2022, has attempted to enter the reimbursement bracket twice, but neither has made it past the first hurdle of CDRC.

Rybrevant is the first bispecific antibody therapy approved for the treatment of EGFR exon20 insertion NSCLC. It ushered in the era of targeted therapies by demonstrating a high overall response rate (ORR) of 40 percent in this disease, which has a poor prognosis due to the lack of effective treatment options.

In addition, Exkivity (mobocertinib), which was approved for the same cancer type as Rybrevant, voluntarily withdrew its marketing authorization in the U.S. last year due to the failure of a confirmatory clinical trial, and its approval and reimbursement status in Korea have become unclear.

For these reasons, Rybrevant is recommended for the second-line treatment of EGFR exon20 insertion NSCLC in leading domestic and international guidelines, such as the U.S. National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and American Society of Clinical Oncology (ASCO), in addition to the Korean Association for Lung Cancer (KALC)’s guidelines, which were revised for the first time in 12 years last year.

Janssen Korea has reportedly submitted additional evidence, including Korean single-center real-world data, for a third reimbursement challenge for Rybrevant.

The real-world study, which included 42 patients treated with Rybrevant at Samsung Medical Center from January 2018 to June 2022, confirmed similar or higher efficacy to the licensed CHRYSALIS study (objective response rate of 33 percent, disease control rate of 76 percent, median progression-free survival of 11.8 months, and median overall survival of 27.2 months).

"Considering the low survival rate of rare lung cancer patients, there is an urgent need to address the issue of access to therapeutics that have demonstrated clinical utility through phase 2 trials or real-world studies," said Professor Ahn Jin-seok of the Department of Hematology-Oncology at Samsung Medical Center. "It is difficult to conduct phase 3 trials with a control group because the number of rare lung cancer patients is significantly small and the expected survival time is less than one year."

Professor Ahn noted that most patients with rare lung cancers would like to be treated with targeted anticancer drugs that have QOL (quality of life) and efficacy advantages over conventional chemotherapy if not for the high price barrier.

"In particular, access to rare lung cancers, such as EGFR exon 20 insertion mutations that are refractory to conventional therapies, should be improved,” Ahn said. “I hope that Rybrevant will be evaluated and introduced in Korea under a compassionate use program to bring hope and help to more patients."

Rybrevant is also covered by public benefits in three of the eight A8 countries that Korea uses for new drug reimbursement—the United States, Switzerland, and Italy—and has met the requirements for exemption from economic viability assessment.

Amid mounting calls from patients and medical professionals for reimbursing Rybrevant, all parties involved are watching whether the drug can facilitate the receipt of insurance benefits for rare lung cancer treatments.