Welireg and VHL Disease

On August 13, 2021, the US Food and Drug Administration (FDA) approved Belzutifan [pronounced bell-ZOO-ti-fan] (Welireg) for the treatment of renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET) and hemangioblastomas (HB) in adult VHL patients. The medication is now available to be prescribed in the US.

How do you take it and what are the possible side effects?

  • Belzutifan is an oral HIF2alpha inhibitor drug that is taken once a day, every day.
  • The daily dose is 120 mg (three pills of 40 mg each) taken approximately the same time every day with or without food.
  • Belzutifan is generally well tolerated. The most frequent side effect is mild or moderate anemia (low red cells, hematocrit and hemoglobin), which may cause some fatigue or headaches. One out of five patients may develop mild joint and/or muscle aches, stomach upset and/or diarrhea.
  • The effect of belzutifan on male or female fertility is NOT known. Pregnant women should not receive it. Until more information is available, patients interested in having children may consider sperm or egg banking.
  • Future clinical studies will clarify what is the optimal time to start and possibly stop treatment with belzutifan to maximize the effect of the medication in treating VHL-related tumors.

What should patients do if they want to find out more about belzutifan and if it’s right for them?

VHL patients should discuss whether or not they should be treated with this medication and how (should they start treatment when drug is available or later, what is the end goal, etc) with their personal physicians. It is extremely important to note that patients who wish to go on belzutifan should be fully up-to-date on their scans and surveillance. We encourage VHL patients and their physicians to talk to VHL expert physicians at the designated VHL Clinical Care Centers (CCC). A list of CCCs and contact information can be found here.

What impact does it have on VHL-related tumors?

  • In a multi-site phase 2 clinical trial, belzutifan reduced the size of 30% of pNETs, 40% of RCC and 60% of HBs (known as a partial response)
  • Complete disappearance of the tumor (called complete response) is very rare.
  • Importantly, the drug stopped tumor progression in almost 90% of VHL patients over the 3 years of study duration.
  • Both the solid part and the cystic part of the tumors shrunk with treatment
  • It may take several months of treatment (4-6 or more) for belzutifan to start shrinking a tumor. For this reason, it may not be appropriate to treat patients who need immediate surgery with belzutifan.
  • We do not know what is the optimal duration of the treatment with Belzutifan
  • Belzutifan does not “cure” VHL disease, it only treats the specific tumors for which it was approved for.
  • We do NOT know the effect or role of belzutifan in preventing tumor formation and future studies should address the values of the drug in prevention.

The VHL Alliance will continue to update the community as more information becomes available. More information about VHL-related clinical trials can be found here.