The OS barrier to CDDC review and reimbursement in Korea

Without OS data, passing the committee is exceptionally difficult…Gap between regulatory approval and reimbursement continues to widen

Two CDK4/6 inhibitors that were reviewed simultaneously produce contrasting outcomes

Beyond its roughly 50% approval rate, there is little dispute that the Cancer Disease Deliberation Committee (CDDC) has become the highest hurdle in Korea's oncology reimbursement process.

Originally established as a committee of prescribing physicians tasked with evaluating the clinical usefulness of cancer drugs seeking reimbursement, the CDDC became the center of controversy after 2020 when it began formally considering budget impact in addition to clinical value.

The fact that a committee that used to review a drug’s usefulness began reviewing fiscal impact became an issue, as budget considerations are already addressed later in the reimbursement process by bodies such as the Pharmacoeconomic Evaluation Subcommittee and the Drug Reimbursement Evaluation Committee (DREC). Criticism intensified when physician members of the CDDC began opposing reimbursement for certain therapies based not only on medical judgment but also on pharmacoeconomic considerations.

From a clinical perspective, it can appear counterintuitive for physicians who treat patients to oppose the reimbursement of new therapies. For physicians who prescribe the drugs, the more treatment options there are, the better. As a result, CDDC members have become a top priority for pharmaceutical companies seeking reimbursement approval.

Don't expect to pass CDDC review without OS data

Controversies surrounding the CDDC have included issues such as the composition of committee members, transparency, and fairness. Among them, one factor has increasingly been viewed as almost a guaranteed predictor of failure: the absence of overall survival (OS) data.

OS measures the time from the start of treatment until death from any cause. Because patient outcomes vary widely, OS is generally reported as a median rather than an average. Patients who remain alive at the time of analysis are censored at their longest observed follow-up. Naturally, demonstrating an OS benefit requires lengthy follow-up periods.

For this reason, oncology drugs are often approved initially based on progression-free survival (PFS) data, with OS evidence submitted later.

PFS measures the length of time during which a patient remains alive without disease progression. Historically, PFS was widely accepted as a meaningful clinical endpoint. Many physicians continue to argue that “neither OS nor PFS should be viewed as inherently superior to the other.” However, under the growing influence of CDDC, some believe PFS has effectively become insufficient on its own.

According to DailyPharm’s coverage, among solid-tumor therapies that underwent pharmacoeconomic evaluation and sought new reimbursement listings or reimbursement expansions over the past three and a half years, only a handful of products, including Lecluza, successfully passed the CDDC without OS data. While some hematologic malignancy treatments have obtained reimbursement without demonstrating OS benefits, in the field of solid tumors, the absence of OS data effectively leads to failure.

Even in the adjuvant treatment setting, which is often regarded as one of the most challenging areas for reimbursement approval, therapies that successfully secured reimbursement generally did so only after obtaining OS data.

However, officials from both the Ministry of Health and Welfare and the Health Insurance Review and Assessment Service (HIRA) emphasized, “We do not look solely at OS. The CDDC evaluates clinical usefulness, social need, budget impact, and other factors to make fair and balanced decisions."

Two drugs that were simultaneously reviewed at the CDDC level

A recent case illustrates the issue. At last month's CDDC meeting, two drugs with the same mechanism of action were reviewed simultaneously for similar reimbursement expansions, to meet contrasting results. The drugs were the CDK4/6 inhibitors ‘Verzenio’ and ‘Kisqali.’

Both sought reimbursement expansion for adjuvant treatment of early breast cancer, but only Verzenio passed review. The key difference was that Verzenio had generated OS data, while Kisqali had not yet done so.

The simultaneous review of the two drugs attracted significant attention. Verzenio itself had previously failed 3 separate CDDC reviews before obtaining OS data. First submitted in May 2023, the product remained more than 3 years without reimbursement coverage.

The fact that a drug repeatedly rejected due to lack of OS evidence was later reviewed alongside a same-class competitor that also lacked OS data sparked intense interest. Industry and academic observers argued over whether the committee would apply a class effect approach or continue to place primary emphasis on demonstrated OS benefits.

One medical oncology professor who previously served on the CDDC said, “It is very difficult for a solid tumor drug to pass CDDC review without OS data. There is even a growing sentiment among committee members that 3-year OS data may not be enough. If the current trend continues, companies may eventually need even longer-term OS evidence to secure CDDC approval."