'Vadanem' prescription strategies specified

From an alternative to an ESA choice

Specific timing suggested for dialysis and non-dialysis patients... discussion on treatment switching

Differentiation based on Hb response and iron metabolism... Focus on clinical utility

The scope of Vadanem (vadadustat), a treatment for renal anemia, is expanding in clinical practice beyond being a simple alternative to Erythropoiesis-Stimulating Agents (ESAs). This follows the growing need for a patient-centered approach that considers application criteria based on dialysis status, the timing of treatment switching, and the specific characteristics of iron metabolism and the hemoglobin (Hb) response.

Tanabe Pharma Korea and HK inno.N recently held the ‘New Paradigm VADANEM Symposium’ in Seoul to share clinical application strategies, focusing on application criteria by dialysis status, treatment switching timing, and the characteristics of iron metabolism and Hb response.

On the first day, chaired by Professor Bum Soon Choi (Catholic Univ. College of Medicine), presentations were given by Professor Dong Ki Kim (Seoul National Univ. College of Medicine) and Professor Sungjin Jung (Catholic Univ. College of Medicine). On the second day, chaired by Professor Kwon-Wook Ju (Seoul National Univ. College of Medicine), the session featured presentations by Professor Gang Jee Ko (Korea Univ. College of Medicine) and Professor Eun Sil Koh (Catholic Univ. College of Medicine).

Symposium commemorating the launch of Vadanem.

Application strategies vary by dialysis status and ESA response

Vadanem is an oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI) that signals a shift away from the existing injection-centered treatment structure, dominated by ESAs. It has recently improved patient access following its inclusion in the domestic health insurance reimbursement list.

However, experts reached consensus that a granular application strategy based on patient status is required in clinical practice, rather than solely on the convenience of an oral medication.

Renal anemia is characterized by decreased erythropoietin (EPO) production as Chronic Kidney Disease (CKD) progresses, often accompanied by 'functional iron deficiency.' As hepcidin increases due to inflammation, a state arises in which iron cannot be utilized even when there is sufficient iron in the body.

Given such an environment, 'ESA hyporesponsiveness,' where response to ESA treatment is poor, becomes an issue. Experts explained that for many patients, maintaining Hb levels is difficult despite high doses of ESA.

Professor Dong Ki Kim said, "Since sufficient clinical experience with ESA treatment has been accumulated for dialysis patients, we should consider Hb variability and stability rather than simply switching drugs. New options can be reviewed for patients who have difficulty maintaining target Hb or experience high variability in existing treatments."

He added, "For non-dialysis patients, the fact that it is an oral medication can serve as a significant variable in treatment selection. An approach that considers oral options from the initial treatment stage is entirely feasible."

Additionally, it was noted that Vadanem could be considered an alternative for patient groups in whom Hb response is insufficient or variability is high despite ESA treatment. It was emphasized that the stability of Hb maintenance and treatment sustainability should be evaluated alongside simple numerical improvements.

Experts suggested the following as potential patients for Vadanem ▲Patients with ESA hyporesponsiveness ​▲Patients with concurrent inflammation ▲Non-dialysis patients with a high burden of injection therapy. ​A key point mentioned was that improvements in iron utilization efficiency can be expected in patients with functional iron deficiency.

Another characteristic of Vadanem is its mechanistic differentiation regarding iron metabolism regulation. As it increases the efficiency of iron utilization in the body through the HIF pathway, analysis suggests that its coordination with iron supplementation strategies may differ from that of existing ESAs.

Vadanem does not simply supplement EPO.It possesses a mechanism that induces "complete erythropoiesis" by simultaneously regulating iron absorption, transport, and utilization.

Professor Sungjin Jung said, "HIF-PHI class treatments have the characteristic of regulating Hb more physiologically through mechanisms linked to iron metabolism. The fact that Hb increase patterns may appear differently compared to ESAs must be considered clinically."

He emphasized, "Since treatment response can vary depending on iron status, an approach that evaluates iron metabolism indicators along with Hb levels is necessary."

Symposium commemorating the launch of Vadanem.

Hb response and iron metabolism variables…"Patient-specific approaches needed"

Presenters explained that setting treatment goals based on patient characteristics is important, especially since the focus can be on maintaining Hb stably within a more physiological range rather than a rapid surge.

For prescriptions, a strategy was suggested to start with 300 mg of Vadanem once daily, maintain it for a period, and then increase the dose based on response. It was emphasized that closely monitoring the rate of Hb increase in the early stages is crucial, and that dose adjustments are necessary if Hb rises too sharply.

Furthermore, discussions on the timing of treatment switching continued. Switching to Vadanem can be a strategy for patient groups with declining response or side effect concerns during ESA treatment, and the possibility of considering oral agents from the initial treatment stage is expected to expand.

Professor Gang Jee Ko said, "For patients whose ESA doses must be continuously raised or who have difficulty maintaining target Hb, treatment strategies need to be reviewed. For these patient groups, switching to Vadanem can be a realistic option."

She added, "If a burden or compliance issue regarding injections arises during long-term treatment, switching to an oral agent is meaningful for patient management."

Professor Koh Eun-sil also emphasized, "In the future, a trend may emerge where oral agents are considered as initial treatment options rather than just alternatives after ESA. It is important to flexibly design treatment strategies considering patient characteristics."

Additionally, Professor Ko mentioned the need for managing drug interactions due to the nature of oral medications.

Professor Ko concluded by explaining that "When co-administered with iron supplements or phosphate binders, drug absorption may decrease, so it is recommended to stagger administration times. Dose adjustments may also be necessary when co-administered with certain other drugs."