Cancer experts propose ‘integrated review system' for IHC-based companion diagnosis

The Korean Society of Pathologists has taken issue with the “diagnostic gaps” that inevitably occur in clinical practice due to the procedural limitation of “technical evaluation” in the reimbursement evaluation process at the Health Insurance Review and Assessment Service (HIRA) after the Ministry of Food and Drug Safety (MFDS) approved in vitro companion diagnostic devices.

One way to solve this problem is for the society to propose an “integrated review” system in which the MFDS, the National Evidence-based Healthcare Collaborating Agency (NECA), and HIRA conduct simultaneous approval and technical evaluation.

At a debate to improve the companion diagnosis system to strengthen cancer treatment outcomes held at the National Assembly on Thursday, members of the executive board of the Korean Society of Pathology emphasized the need for an “integrated review” system and pointed out the limitations of the current system.

At the debate, Professor Lee Hye-seung of the Department of Pathology at Seoul National University Hospital, who is the society’s general affairs director, and Professor Won Jae-kyung of the Department of Pathology at Seoul National University Hospital, the society’s insurance director, gave their presentations on “Changes in the paradigm of cancer treatment and the importance of companion diagnosis.”

“Companion diagnostics is a key technology that enables customized treatment tailored to the characteristics of patients in cancer treatment,” Professor Lee said. “By analyzing specific genes or proteins in cancer cells to select patients who will respond to targeted therapies, we can avoid unnecessary treatment and maximize the effectiveness of treatment.”

Lee continued, “Companion diagnostics also contribute to the efficient use of healthcare resources and the financial health of health plans. By targeting targeted therapies to the right patients, we can reduce unnecessary side effects and healthcare costs.”

Professor Lee noted that companion diagnostics play an essential role in evaluating the efficacy and safety of targeted therapies.

“Targeted therapeutics target specific genes or proteins and cannot be screened without companion diagnostics. Companion diagnostics and therapeutics are interdependent, and delays in the approval or introduction can significantly disrupt patient care,” Lee added, emphasizing the need for simultaneous access to companion diagnostics and medicines.

Professor Won criticized the limitations of the current companion diagnostic system related to immunohistochemistry (IHC), one of the representative companion diagnostic technologies, pointing out that simultaneous access to companion diagnostics and medicines is seriously compromised.

“IHC companion diagnostic technology has been standardized globally for decades, and its safety and efficacy have already been established,” Won said. ‘Notably, it is highly reproducible using automated instruments and validated reagents, and is used for various cancer types, including HER2, PD-L1, and ALK.”

“HIRA requires new medical technology evaluation for IHC tests for new biomarkers. As a result, it takes up to 15 months for a companion diagnostic device (CDx) to be introduced into the clinical field even after approval by the KFDA due to the new medical technology evaluation process.” Professor Won said. “Evaluating the already established IHC companion diagnostic as a new medical technology is inefficient, which prevents patients from receiving timely treatment.”

The Korean Society of Pathologists proposes to improve the IHC companion diagnostic system for the implementation of precision medicine,” Won said. The professor added that for proven IHC companion diagnostic technologies, a quick “existing technology classification plan” should be established, and the technology should be designated as a target for “integrated review”' from the approval stage of the MFDS to strengthen simultaneous access to therapeutics after approval.

“Rapid and accurate IHC companion diagnostics can enable customized patient treatment, minimizing unnecessary side effects and medical costs. This can improve the treatment outcomes and quality of life of cancer patients and contribute to the efficiency of health insurance finances by reducing the burden of costly cancer treatment,” Won said. “Improved diagnostic accuracy and rapidity can also significantly improve the efficiency of medical staff.”

Professor Won continued, “The rapid adoption of companion diagnostics promotes the development of precision medicine technology and expands opportunities for domestic companies developing anticancer drugs and in vitro diagnostic devices to enter the global precision medicine market, which benefits the government, patients, medical staff, and industry, and can contribute to strengthening national competitiveness and improving the health level of the population in the long term.”

Professor Rha Sun-young of the Department of Oncology at Severance Hospital, who is also the president of the Korean Cancer Association, cited the companion diagnostic devices Vyloy (zolbetuximab) and Claudin18.2, which recently received simultaneous approval from the MFDS, as a clinical example of the blind spots in the current IHC companion diagnostic system.

Professor Rha emphasized the pathophysiology of gastric cancer, which makes it difficult to develop targeted therapies compared to other cancers, especially lung cancer, noting that the difference in treatment outcomes between the two cancers over the past few decades demonstrates the effectiveness of targeted therapy.

She explained the clinical value of Claudin 18.2, which has emerged as a therapeutic target for gastric cancer. She emphasized the need for rapid clinical introduction of the recently introduced Vyloy.

“After HER2, Claudin 18.2 has emerged as a new target for the treatment of gastric cancer and can significantly extend the survival of patients with gastric cancer,” Professor Rha said. “Notably, the recently approved zolbetuximab demonstrated a median overall survival of 30 months in Claudin 18.2-positive patients in a sub-analysis of Korean patients, more than double that of conventional therapy.”

“The companion diagnosis is delaying the adoption of these innovative treatments count review and new technology assessment,” Rha said. “Applying the new technology assessment to already established technologies is inefficient and takes away patient treatment opportunities.”

Another panelist, Lee Eun-young, director of the Korea Alliance of Patient Organizations, echoed the Korean Society of Pathologists' proposal for an “integrated review” system. She cited the government's recent approval-evaluation linkage system, established to speed up the introduction of life-saving drugs, as an example. She emphasized that it could be applied to companion diagnostics.

“Recently, the first drug in the pilot project of the approval-evaluation linkage system was approved for reimbursement in 5.5 months, significantly shortening the time from approval to reimbursement,” Lee said. “This expedited process provides an important opportunity for patients to receive timely treatment.”

“Even after the MFDS’ approval, companion diagnostics that are indispensable to targeted therapies can take upwards of 15 months for technical evaluation. Delays in diagnosis mean delays in treatment, which can be life-threatening for patients with cancer and rare diseases who need treatment urgently,” Lee said. “As with drugs, companion diagnostics are also important for approval. If we can create a system where companion diagnostics can be reviewed for authorization and reimbursement in parallel, just like medicines, patients can get diagnosed and start treatment faster.”