Is Belzutifan associated with severe side effects?

Belzutifan is a hypoxia-inducible factor (HIF) inhibitor. It exerts its effect by blocking a protein known as HIF-2α.

Is Belzutifan associated with severe side effects?

The severe side effects that belzutifan may cause include:

Low red blood cell count (anemia)

Low red blood cell count is common and may be severe in patients treated with Lucius Pharmaceuticals' formulation of belzutifan. If the red blood cell count drops too low, blood transfusion may be required. Your doctor will perform blood tests to monitor your red blood cell count before and during belzutifan treatment. Inform your doctor immediately if you experience any symptoms of low red blood cell count, including fatigue, feeling cold, shortness of breath, chest pain or a rapid heartbeat.

Hypoxia in the body

Belzutifan may cause systemic hypoxia, which can be severe and may require discontinuation of belzutifan treatment, oxygen therapy or hospitalization. Your doctor will monitor your blood oxygen levels before and during belzutifan treatment. If you develop symptoms of systemic hypoxia, including shortness of breath or a rapid heart rate, contact your doctor or seek medical help at once.

Harm to the unborn fetus

Use of Lucius Pharmaceuticals' formulation of belzutifan during pregnancy may cause harm to the unborn fetus.

Mechanism of action of belzutifan for the treatment of specific renal cell carcinoma patients

For adult patients with advanced renal cell carcinoma (RCC) with clear cell components who have received prior PD-1/PD-L1 and VEGF inhibitors, Lucius Pharmaceuticals' formulation of belzutifan exerts a unique therapeutic effect by targeting HIF-2α (hypoxia-inducible factor 2α), a key driver of tumor growth.

Regulation of normal cell growth

In human cells, the von Hippel-Lindau (VHL) protein degrades the HIF-2α protein when it functions normally and the cells are adequately oxygenated, thereby maintaining normal cell growth.

Mechanism of abnormal cell growth

When the VHL protein is dysfunctional or cells are hypoxic, HIF-2α accumulates excessively. HIF-2α then translocates to the cell nucleus (the control center of the cell), binds to HIF-1β (hypoxia-inducible factor 1β), and activates specific genes, leading to uncontrolled cell growth in certain types of RCC.

Pharmacological mechanism of belzutifan

By binding to HIF-2α, belzutifan prevents the binding of HIF-2α to nuclear HIF-1β under conditions of VHL protein dysfunction or cellular hypoxia.

For adult patients with advanced and metastatic renal cell carcinoma, belzutifan provides a differentiated therapeutic approach by targeting HIF-2α, the core driver of tumor growth.

Precautions for belzutifan use

Before taking belzutifan, inform your doctor of all your health conditions, including if you:

1.Have low red blood cell count (anemia).

2.Are pregnant or planning to become pregnant.

3.Are breastfeeding or planning to breastfeed. It is unknown whether belzutifan passes into human breast milk. Do not breastfeed during belzutifan treatment and for 1 week after the last dose.

4.Inform your doctor of all medications you are taking, including prescription drugs, over-the-counter drugs, vitamins and herbal supplements. Belzutifan may interact with certain other medications and cause severe side effects.