Will Trodelvy get innovative new drug status backed by 100,000 petitions?

As the government will likely reflect innovative new drug values on its reimbursement criteria this year, expectations are rising for the coverage of triple-negative breast cancer drug Troldelvy (acituzumab govitecan), which has garnered 100,000 petitions.

In April, the Ministry of Health and Welfare announced its policy to flexibly apply cost-effectiveness evaluation acceptance to drugs that meet the criteria for innovation under the Second Comprehensive National Health Insurance Plan’s 2024 Implementation Program. To this end, the ministry plans to finalize the new drug’s innovativeness criteria and revise related regulations in the first half of this year.

Korea uses the incremental cost-effectiveness ratio (ICER) to evaluate the appropriateness of new drugs for health insurance coverage. The ICER is a value calculated by comparing the cost of a new drug to the cost of an existing treatment for a patient to live a healthy life for one year. If the ICER is higher than a certain threshold, it is considered unaffordable by health plans.

However, with the recent advancement of new drug technologies, the cost of drugs is increasing, with many experts pointing out that the threshold should be more flexible depending on the innovation of the new drug.

For example, according to a study titled "Survey on Unmet Needs of the New Drug Listing System," published in the online edition of Springer in 2023, the satisfaction level of the Korean pharmaceutical companies' drug pricing managers with the recognition of the value of new drug innovations was only 1.6 out of 5, with 92.9 percent citing the improvement of the ICER threshold as subject to improvement in economic evaluation.

Accordingly, the government announced its intention to flexibly apply the ICER threshold to ensure innovation value for new drugs that meet the following criteria; there is no substitute or therapeutically equivalent product or treatment; clinically meaningful improvement, such as significant prolongation of survival, is demonstrated; and the drug is approved as a new drug through the Global Innovative product for Fast Track (GIFT), U.S. Food and Drug Administration (FDA)’s Breakthrough Therapy Designation (BTD), or European Medicine Agency (EMA)’s PRIority MEdicines (PRIME) system.

With the prospect of preferential economic evaluation for innovative new drugs on the horizon, attention has turned to one drug that meets all of these definitions -- Trodelvy.

Troldelvy is the only drug that has been shown to prolong overall survival in large-scale clinical trials in the second-line treatment of metastatic triple-negative breast cancer for which there are no treatment options other than chemotherapy.

The U.S. National Comprehensive Cancer Network (NCCN) guidelines recommend Troldelvy as a Category 1, the highest level of recommendation, and the European Society for Medical Oncology (ESMO) awarded Troldelvy a maximum score of 5 in the ESMO-MCBS, a rare achievement for a treatment for late-stage cancer. In 2016, the drug was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration, fulfilling the last requirement.

Troldelvy has also received benefits since July 2022 in the United Kingdom, one of the most conservative countries in reimbursement.

In the U.K., the range of ICER thresholds is flexible, depending on the severity of the disease, unmet need, and the innovation of the drug. The typical threshold is £20,000 to £30,000, but the threshold is increased to £50,000 for treatments that demonstrate a survival benefit of three months or more in a small patient population with a life expectancy of less than 24 months. In addition, a weighted threshold will be applied for high-severity diseases.

Trodelvy has been recognized as a life-prolonging treatment for the terminally ill patient population and has been granted an increase from the previous threshold. Results from the phase 3 study showed that overall survival in the Trodelvy arm was 11.8 months, about five months longer than chemotherapy (6.9 months). In addition, the estimated number of patients eligible for Trodelvy was 391, less than those with a rare disease, defined as less than one per 50,000 population.

As a result, the U.K.'s National Institute for Health and Care Excellence (NICE) deemed Trodelvy cost-effective, even though its ICER was measured at around £47,000.

NICE deemed Troldelvy to be an efficient use of the National Health Service (NHS) finance because it met the criteria for treating a terminally ill patient population and significantly improved response rates compared to the standard of care in metastatic triple-negative breast cancer, a disease with high unmet need for effective treatment options.

In particular, NICE highlighted the burden faced by patients with metastatic triple-negative breast cancer due to the lack of effective new drugs. It noted that the nature of triple-negative breast cancer, which requires the use of chemotherapy as standard treatment, causes considerable anxiety and fear for patients and their caregivers. The agency also cited that experts have noted that even when chemotherapy is tried, the disease tends to recur quickly, leaving few treatment options for patients with recurrent metastatic triple-negative breast cancer.

In this situation, Trodelvy demonstrated statistically significant improvements in overall survival, progression-free survival, and objective response rate compared to the standard of care in a phase 3 trial, which led the NICE committee to assess Trodelvy as a highly effective treatment for patients with metastatic triple-negative breast cancer.

Meanwhile, patient demand for Troldelvy to be covered by health insurance in Korea has reached a boiling point.

Two petitions calling for reimbursement have been posted this year, with more than 100,000 signatures, demonstrating the public's interest in Troldelvy.

Last November, Trodelvy passed the Cancer Disease Review Committee and is nearing the deadline for the Pharmaceutical Reimbursement Evaluation Committee's review, drawing attention from patients and caregivers to see if the government's plan to recognize the value of innovative new drugs will fulfill their wishes.