Many medicines are available to treat kidney cancer. Depending on your situation, your health care provide may suggest Welireg (belzutifan) as an option.
Welireg is a once-daily tablet used to treat various types of cancer, including certain types of renal cell carcinoma (RCC) in adults.
Many people with advanced RCC receive combinations of immunotherapy medicines and targeted therapies as their first treatment. (Targeted therapies are medicines that act on specific proteins or signals involved in cancer growth.) However, RCC can eventually become resistant to treatment, meaning the cancer starts growing again.
For other people, Welireg may be used earlier, such as right after surgery, to help reduce the risk of the cancer coming back.
This article answers common questions about Welireg for RCC, including how it works, its potential benefits, and how to take it.
Welireg Side Effects and Interactions: What to Expect and How to Manage Them
Is Welireg Right for Me?
Welireg is FDA-approved to treat certain types of clear cell renal cell carcinoma (RCC) in adults. Depending on your situation, it may be used after surgery to help prevent the cancer from coming back, or to treat cancer that has already spread after receiving certain other treatments.
- Clear cell RCC is the most common type of kidney cancer in adults. It starts in the tiny tubes inside the kidney that help filter blood and make urine. It’s called “clear cell” because the tumor cells often look pale or clear under a microscope.
- “Advanced” means the cancer has spread beyond where it started in the kidney.
To decide if Welireg is right for you, your health care provider will consider factors like the type of cancer you have, how much it has spread, any cancer treatments you have already used, and your overall health.
How Does Welireg Work for RCC?
Cancer cells need oxygen to survive, just like normal cells. But as tumors grow, they can outgrow their blood supply and end up in low-oxygen conditions, called hypoxia.
To survive, cancer cells can switch to pathways that help them continue growing despite low oxygen. One such pathway involves a protein called hypoxia-inducible factor 2 alpha (HIF-2α). In many cases of clear cell RCC, HIF-2α acts as a key driver of tumor growth. HIF-2α can activate signals that help cancer cells grow, spread, and form new blood vessels that feed tumors.
More than 90% of clear cell RCC tumors have changes involving the von Hippel-Lindau (VHL) gene. These changes may include mutations, deletions (missing pieces of the gene), or other alterations that prevent the gene from working properly.
Normally, VHL helps control HIF-2α levels inside cells. But when VHL is not working properly, too much HIF-2α can build up.
Welireg works by targeting HIF-2α. By blocking this protein, Welireg can reduce the signals that tumors use to survive, grow, and spread.
How Was Welireg Studied for RCC?
After a PD-1 or PD-L1 Inhibitor and a Targeted Therapy
A clinical trial called LITESPARK-005 was done to study the effectiveness of Welireg alone for advanced RCC after certain prior treatments had stopped working.
The trial included adults with advanced clear cell RCC (ccRCC) whose cancer was previously treated with certain medicines and had progressed (worsened).
A total of 746 people participated in the study:
- Participants ranged in age from 22 to 90 years old. The median (middle) age was 63 years.
- Most participants were men (78%) and White (79%). Some were Asian (12%) or Black or African American (1%); 11% identified as being of Hispanic or Latino ethnicity.
- Most had already received two or three prior cancer treatments before joining the study.
People in the study were randomly assigned to take either Welireg or another cancer medicine called everolimus once daily. People stayed on treatment as long as it was helping their cancer and side effects remained manageable.
During the study, participants had imaging scans to check their cancer starting nine weeks after they were assigned to a treatment group. After that, scans were repeated every eight weeks until week 49 of the study. After that, scans were done every 12 weeks. These scans helped the researchers monitor whether the cancer stayed the same, shrank, or continued to grow during treatment.
The main goals of the study were to measure:
- Overall survival (OS), or how long people lived after starting treatment.
- Progression-free survival (PFS), or how long people lived without their cancer getting worse.
In Combination with Lenvatinib After a PD-1 or PD-L1 Inhibitor
A clinical trial called LITESPARK-011 was done to study the effectiveness of Welireg in combination with another medicine called lenvatinib for RCC.
The trial included adults with advanced ccRCC whose cancer had grown or spread after treatment with a type of immunotherapy medicine called a PD-1 or PD-L1 inhibitor. It also included people whose cancer came back within 6 months of completing preventive (adjuvant) therapy with a PD-1 inhibitor.
A total of 747 people participated in the study:
- Participants ranged in age from 30 to 86 years old. The median (middle) age was 63 years.
- Most participants were men (76%) and White (87%). Some were Asian (9%), American Indian or Alaska Native (1.6%), multiple races (1.1%), Black or African American (0.4%), or race was not reported (0.8%); 18% identified as being of Hispanic or Latino ethnicity.
- Most had received one prior cancer treatment before joining the study (72%), while 28% had received two or more prior treatments.
People in the study were randomly assigned to take either Welireg plus lenvatinib or another cancer medicine called cabozantinib once daily. People stayed on treatment as long as it was helping their cancer and side effects remained manageable.
During the study, participants had imaging scans to check their cancer every eight weeks for the first 80 weeks. After that, scans were done every 12 weeks.
The main goals of the study were to measure:
- Progression-free survival (PFS)
- Overall survival (OS)
To Help Prevent the Cancer From Coming Back
A clinical trial called LITESPARK-022 was done to study the effectiveness of Welireg in combination with another medicine called pembrolizumab for ccRCC.
The trial included adults with ccRCC at high risk of their cancer coming back who had undergone surgery, and who had not received prior treatment for advanced RCC.
A total of 1,841 people participated in the study:
- Participants ranged in age from 20 to 91 years old. The median (middle) age was 60 years.
- Most participants were men (71%) and White (63%). Some were Asian (29%), unknown race (3.6%), American Indian or Alaska Native (1.7%), multiracial (1.8%), or Black or African American (0.7%); 15% identified as being of Hispanic or Latino ethnicity.
People in the study were randomly assigned to take either Welireg plus pembrolizumab or a placebo (containing no medicine) plus pembrolizumab. People stayed on treatment for up to approximately 54 weeks or until their cancer returned or side effects became unacceptable.
The main goal of the study was to measure disease-free survival (DFS), or how long people lived without their cancer coming back or spreading after surgery.
What Are the Benefits of Welireg Based on the Study?
After a PD-1 or PD-L1 Inhibitor and a Targeted Therapy
Results from the LITESPARK-005 trial showed that Welireg helped some people with advanced RCC live longer without their cancer getting worse compared with everolimus.
In the study, median PFS was 5.6 months in both groups. However, when researchers looked at longer-term results, more people taking Welireg remained alive without cancer progression over time.
PFS at 18 months:
- 24% of people taking Welireg were still alive without cancer progression.
- 8% of people taking everolimus were still alive without cancer progression.
However, the difference in OS was not large enough to know for sure whether Welireg improved survival compared with everolimus.
OS at 18 months:
- 55% of people taking Welireg were still alive.
- 51% of people taking everolimus were still alive.
The study also measured objective response rate (ORR), which looks at how many people’s cancer responded (meaning that the imaging scans confirmed that their tumor partially or completely shrank).
Among participants who had a tumor that doctors could see and measure on imaging scans when the study began:
- 22% of people taking Welireg had a response (19% had a partial response, and 3% had a complete response)
- 4% of people taking everolimus had a response (4% had a partial response, and no one had a complete response)
In Combination with Lenvatinib After a PD-1 or PD-L1 Inhibitor
Results from the LITESPARK-011 trial showed that Welireg plus lenvatinib helped some people with advanced ccRCC live longer without their cancer getting worse compared with cabozantinib.
In the study, people taking Welireg plus lenvatinib lived about 14.6 months before their cancer grew or spread, compared with about 10.6 months for people taking cabozantinib.
When researchers looked at how long people lived overall:
- People taking Welireg plus lenvatinib lived a median of 33.7 months.
- People taking cabozantinib lived a median of 28.6 months.
However, the difference in OS was not large enough to know for sure whether Welireg plus lenvatinib improved survival compared with cabozantinib.
The study also measured ORR. Among participants who had a tumor that doctors could see and measure on imaging scans when the study began:
- 53% of people taking Welireg plus lenvatinib had a response (49% had a partial response, and 4% had a complete response)
- 40% of people taking cabozantinib had a response (39% had a partial response, and 1.1% had a complete response)
Among those who responded to Welireg plus lenvatinib, 63% had their response last 12 months or longer.
To Help Prevent the Cancer From Coming Back
Results from the LITESPARK-022 trial showed that Welireg plus pembrolizumab helped some people with ccRCC live longer without their cancer coming back or spreading compared with placebo plus pembrolizumab.
When researchers looked at two-year results, more people taking Welireg plus pembrolizumab remained alive without their cancer returning.
DFS at 24 months:
- 81% of people taking Welireg plus pembrolizumab were still alive without their cancer returning.
- 74% of people taking placebo plus pembrolizumab were still alive without their cancer returning.
However, overall survival data from this trial were not yet mature at the time of the analysis, meaning it is too early to know for sure whether Welireg plus pembrolizumab improves how long people live overall.
Keep in mind that your results may be different from those seen in the study. Your health care provider can explain how they will monitor your response and what to expect during Welireg treatment.
How Do I Take Welireg?
Welireg comes as a tablet that you swallow whole. The recommended dosage for adults is 120 milligrams (mg) once daily. It is typically taken at the same time each day, with or without food. To take it at the same time each day, you may want to set an alarm or set up a reminder on your phone.
Take Welireg exactly as prescribed. Your health care provider may pause treatment and/or adjust your dose if you have certain side effects while taking Welireg.
Is There Any Cost Assistance Available?
Financial support programs may help reduce the cost of Welireg. The drugmaker offers patient support resources that may include copay savings or other financial help for eligible people.
For more information, call 855-257-3932 or visit the drugmaker’s patient support website. You can also speak to your health care provider or pharmacy staff about assistance programs.
