Korea's first-line treatment market for biliary tract cancer has shifted. AstraZeneca's immunotherapy Imfinzi (ingredient durvalumab) has entered national health insurance coverage. It was listed one step ahead of the competing drug from Merck (MSD), Keytruda (ingredient pembrolizumab). As attention focuses on the first-mover advantage, analysts say the impact on the insurance fund will likely be significant.
The Ministry of Health and Welfare convened the Health Insurance Policy Deliberation Committee on the 25th and approved a new reimbursement standard for the Imfinzi combination therapy (Imfinzi + gemcitabine + cisplatin) as first-line treatment for unresectable locally advanced or metastatic biliary tract cancer. The effective date is Mar. 1.
Coverage applies only to histologically confirmed adenocarcinoma and excludes ampulla of Vater cancer. It specifies stopping gemcitabine and cisplatin after the initial eight cycles of combination therapy. The reimbursement period is one year. However, if no additional clinical results on the optimal dosing period within one year are presented, it will be automatically extended and recognized for up to two years.
◇ "Early prescribing will decide the market's winner"…nonreimbursed patients seen switching
Biliary tract cancer is a representative low-survival cancer. According to the National Cancer Registry statistics, the 5-year relative survival rate for gallbladder and other biliary tract cancers from 2019 to 2023 is 29.0%. That is less than half the overall cancer average (73.7%). Among major cancers, it is the second lowest after pancreatic cancer (17.0%). It is also lower than lung cancer (42.5%) and liver cancer (40.4%).
By stage, the 5-year relative survival rate at the distant metastasis stage is only 4.1%. The proportion of patients eligible for curative resection is not high, and with chemotherapy having long been effectively established as the first-line standard of care, treatment options have been limited.
In this context, the Imfinzi combination therapy received approval from the Ministery of Food and Drug Safety in 2022 as a first-line treatment and entered the market. According to IQVIA, Imfinzi's domestic sales in 2023 were 82.7 billion won, up 58% from the previous year (52.4 billion won). This indicates a certain level of accumulated prescribing experience in the nonreimbursed market.
MSD also obtained approval in 2024 for the Keytruda combination therapy as a first-line treatment and has pursued listing for reimbursement. A Korea MSD official said, "Last month we completed reimbursement listing for second- and third-line treatments," adding, "The first-line reimbursement strategy is just getting underway."
The industry is focusing on the first-mover advantage. With immunotherapies, the more early prescribing experience accumulates, the more clinicians' choices tend to become fixed. An industry source said, "If long-term survival data are secured, there is a high possibility that treatment strategies in clinical practice will form around the drug that is reimbursed first."
Imfinzi has presented long-term follow-up data from a global phase 3 trial showing that the 3-year overall survival (OS) was more than twice that of the chemotherapy control group. After reimbursement takes effect in March, not only new patients but also existing nonreimbursed patients are expected to switch to reimbursed treatment.
◇ The two sides of innovation…if the "reimbursement-passing price" ceiling rises, the burden on the insurance fund increases
The listing also has policy significance. Imfinzi's first-line biliary tract cancer combination therapy is the third case after Enhertu and Trodelvy to be subject to "flexible application of the incremental cost-effectiveness ratio (ICER) threshold."
ICER is an index that quantifies the health improvement gained per additional expense compared with a comparator treatment. Cost-effectiveness is recognized when it is below a certain threshold. It is typically based on per capita gross domestic product (GDP), and in Korea, about 50 million won has effectively been used as a reference line. For anticancer drugs or treatments for rare diseases, flexible application up to about twice that level has been used.
The ministry last year outlined directions for overhauling the drug pricing system, saying it would raise the ICER threshold to an "appropriate level" and introduce a weight-based flexible application model that reflects disease severity, therapeutic benefit, and fiscal impact. In the long term, it plans to build a post-assessment system after expedited listing to improve access to innovative new drugs.
However, some warn that as ICER flexible application cases accumulate, the government's bargaining power on drug prices could be structurally weakened. The concern is that as precedents of "this drug also passed" pile up, the average price level of new innovative drugs could face upward pressure.
While expanding patient access is meaningful, as the share of drug expenditure grows, pressure to raise premiums and debates over fiscal sustainability are expected to be unavoidable. Health insurance drug spending in 2024 was close to 27 trillion won, and recently the growth rate of drug spending has outpaced the growth rate of total medical expenses. In particular, spending on high-priced anticancer drugs increased at an average annual rate of 12.9% between 2020 and 2023.
Previously, 13 academic experts issued a joint opinion analyzing the government's reform plan, saying it "could pose a serious risk to the sustainability of the health insurance fund," and noted that a more systematic and proactive price management plan for high-priced medicines should be established first.
They said, "There has not been sufficient scientific evidence presented that the current ICER threshold is excessively low," and pointed out that "flexible application by disease severity and raising the threshold should be conceptually distinguished."
The opinion was signed by Professors Kwon Hye-young (Mokwon University), Kim Yun-hee (Inha University), Kim Jin-hyun (Seoul National University), Bae Seung-jin (Ewha Womans University), Bae Eun-young (Gyeongsang National University), Yang Bong-min (Seoul National University), Yoo Soo-yeon (Kangwon National University), Lee Sang-il (University of Ulsan), Lee Tae-jin (Seoul National University), Lee Hye-jae (Korea National Open University), Cho Eun (Sookmyung Women's University), Heo Sun-im (University of Seoul), and Hong Ji-hyung (Gachon University).
Civic groups also express concern that the government's easing stance on the drug pricing system could worsen the health insurance fund. The Citizens' Coalition for Economic Justice, the Korean Pharmacists for a Healthy Society, and the Korea Severe Disease Association held a press conference early this month and demanded, "When listing drugs quickly, the government must disclose the transparent scale of the expected fiscal needs and specific funding plans."
◇ Opening access while binding the budget…the government "will actively use risk-sharing agreements"
Kim Yeon-suk, director of the Pharmaceutical Benefits Division at the Ministry of Health and Welfare, said regarding the reset of the ICER threshold, "We do not yet have specific standards or a framework," adding, "We plan to promote a research project through the Health Insurance Review & Assessment Service." Kim added, "As high-priced new drugs increase, there is a need to use the risk-sharing agreement (RSA), which shares risks with pharmaceutical companies, more actively than now."
On concerns surrounding expedited listing, Kim said, "The aim is to streamline procedures to bring in clinically meaningful drugs quickly," adding, "We take it as a call to design the system more tightly, and we will continue communicating with the field as we make improvements."
RSAs are divided into three types: refund, expenditure cap, and performance-based refund. AstraZeneca signed refund and expenditure cap RSAs this time. Under the refund type, the pharmaceutical company refunds to the insurance corporation a certain percentage of the drug's billed amount. Under the expenditure cap type, if the annual billed amount exceeds the predetermined annual expenditure, the company refunds to the corporation a certain percentage of the excess.
According to the National Health Insurance Service, about 1,805 patients are expected to newly benefit from expanded reimbursement for Imfinzi as first-line treatment for biliary tract cancer. The additional annual fiscal need is expected to be 119.8 billion won (126.1 billion won including patient copayments). However, considering the RSA, the actual burden on the insurance fund could be lower than this.
An NHIS official said, "While expanding Imfinzi reimbursement has the effect of improving patient access, the fiscal impact is also expected to be considerable," adding, "We plan to manage the price and the total amount through RSAs." The official added, "If drug spending increases beyond a certain level, we will pursue post-control through volume–price linkage negotiations."