Does WELIREG (belzutifan) cure brain cancer?

A patient asked me yesterday if this drug cured cancer. She apparently heard Elon Musk saying this at a conference on YouTube. While, I cannot vouch for the reliability of the video, this is the latest on this drug.

The following blog post synthesizes the FDA label, landmark clinical trials (LITESPARK-001, -004, -005, -015), NCCN guidelines, and peer-reviewed literature to present an accurate, evidence-based picture of this drug.

WELIREG (Belzutifan): The Truth About a Groundbreaking Cancer Drug — What It Can and Cannot Do

Belzutifan, sold under the brand name WELIREG, has been making headlines as a revolutionary cancer drug. Some public figures have amplified claims about its potential, including suggestions that it can "cure brain cancer." But what does the science actually say? This post separates fact from fiction using published clinical trial data and FDA-approved labeling.

What Is WELIREG (Belzutifan)?

WELIREG is a first-in-class oral medication that inhibits a protein called hypoxia-inducible factor 2-alpha (HIF-2α). HIF-2α is a transcription factor that helps cells adapt to low-oxygen environments. In certain cancers — particularly those driven by mutations in the VHL (von Hippel-Lindau) gene — HIF-2α accumulates unchecked, switching on genes that promote tumor growth, blood vessel formation, and cancer spread.

By blocking HIF-2α, belzutifan essentially shuts down a key molecular engine driving these specific cancers.

What Is WELIREG FDA-Approved to Treat?

As of 2025, WELIREG has three FDA-approved indications:

1. Von Hippel-Lindau (VHL) Disease: For adults with [VHL disease](https://www.openevidence.com/rare-disease/von-hippel-lindau-disease) who need treatment for associated kidney cancer (renal cell carcinoma), brain/spinal cord [hemangioblastomas](https://www.openevidence.com/rare-disease/hemangioblastoma), or pancreatic neuroendocrine tumors — when immediate surgery is not required.

2. Advanced Kidney Cancer (Renal Cell Carcinoma): For adults with advanced clear cell RCC who have already been treated with both a PD-1/PD-L1 immunotherapy and a VEGF-targeted therapy.

3. Pheochromocytoma or Paraganglioma (PPGL): For patients aged 12 and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma — rare tumors of the adrenal glands and related tissues.

The Clinical Evidence: What the Trials Show

VHL Disease (LITESPARK-004): This landmark trial enrolled 61 patients with VHL disease. After nearly 5 years of follow-up, the objective response rate (ORR) for kidney tumors reached 70%, with 90% for pancreatic neuroendocrine tumors and 50% for CNS hemangioblastomas. Critically, the need for surgery dropped dramatically — from 75% of patients requiring surgery in the 5 years before treatment to only 31% after starting belzutifan. Most patients (57%) remained on treatment after 5 years.

Advanced Kidney Cancer (LITESPARK-005): In a head-to-head trial of 746 patients comparing belzutifan to everolimus, belzutifan showed a statistically significant improvement in progression-free survival (HR 0.75) and a much higher response rate (22% vs. 3.6%).

Pheochromocytoma/Paraganglioma (LITESPARK-015): In this phase 2 trial, belzutifan achieved a 26% objective response rate and 85% disease control rate in a cancer type with very few treatment options. This led to FDA approval in 2025.

The "Brain Cancer Cure" Claim: What's True and What's Not

This is where precision matters enormously. The claim that WELIREG "cures brain cancer" conflates two very different things:

What IS true:

- Belzutifan is effective against CNS hemangioblastomas — benign vascular tumors that occur in the brain and spinal cord of patients with VHL disease. These are NOT what most people mean by "brain cancer."

- In VHL patients, belzutifan achieved response rates of 30–76% in CNS hemangioblastomas (depending on how tumors were measured), with durable responses lasting years.

- It can shrink both the solid tumor and the associated fluid-filled cysts that compress brain tissue, potentially sparing patients from risky neurosurgery.

- The NCCN Guidelines list belzutifan as "useful in certain circumstances" for VHL-associated CNS hemangioblastomas.

What is NOT true:

- Belzutifan does NOT work against glioblastoma (GBM) — the most common and deadly primary brain cancer. In the LITESPARK-001 trial's glioblastoma cohort, 25 patients with recurrent GBM were treated with belzutifan. The objective response rate was 0%. The clinical benefit rate was only 8%, and median progression-free survival was a dismal 1.4 months.

- A 2023 JAMA review on glioblastoma explicitly noted that "unlike other intracranial tumors, which respond to small molecule inhibitors... glioblastomas have been largely unresponsive to molecularly targeted therapy."

- Belzutifan is not approved, indicated, or recommended for glioblastoma or any primary malignant brain tumor.

The bottom line: Calling belzutifan a "brain cancer cure" is misleading. It treats specific benign tumors in the brain that arise from a rare genetic condition (VHL disease). It has zero demonstrated efficacy against glioblastoma or other malignant brain cancers.

How Is WELIREG Taken and What Are the Side Effects?

WELIREG is taken as an oral tablet, 120 mg once daily (80 mg for pediatric patients under 40 kg), with or without food. Treatment continues until disease progression or unacceptable toxicity.

Key side effects include:

- Anemia (the most common, affecting 88–96% of patients across trials): This is an "on-target" effect because HIF-2α regulates erythropoietin production. Most cases are grade 1–2 and manageable with monitoring, transfusions, or erythropoiesis-stimulating agents.

- Fatigue (52–66%)

- Hypoxia (low oxygen levels, up to 15% in advanced RCC): Requires oxygen saturation monitoring before and during treatment.

- Other common effects: Headache, dizziness, nausea, increased creatinine, musculoskeletal pain.

Critical warnings:

- Embryo-fetal toxicity (Boxed Warning): WELIREG can cause fetal harm. Pregnancy must be ruled out before starting treatment. Women must use non-hormonal contraception because belzutifan can make hormonal birth control pills ineffective.

- Drug interactions: Belzutifan induces CYP3A4, which can reduce the effectiveness of many co-administered medications. UGT2B17 or CYP2C19 inhibitors can increase belzutifan exposure and toxicity.

What Makes WELIREG Genuinely Groundbreaking?

Even without the exaggerated claims, belzutifan represents a genuine scientific milestone:

1. First-in-class mechanism: It is the first HIF-2α inhibitor ever approved, validating decades of research into oxygen-sensing pathways (work that earned the 2019 Nobel Prize in Physiology or Medicine).

2. Paradigm shift in VHL disease: Before belzutifan, VHL patients faced a lifetime of repeated surgeries — often losing kidneys, vision, and neurological function along the way. Belzutifan offers the first systemic medical alternative, dramatically reducing surgical burden.

3. Expanding indications: From VHL disease to advanced kidney cancer to pheochromocytoma/paraganglioma, the drug's approved uses continue to grow based on rigorous clinical evidence.

4. Durable responses: In VHL disease, responses have lasted over 5 years in many patients, with 57% still on treatment at the 5-year mark.

The Takeaway

WELIREG (belzutifan) is a genuinely important drug that has transformed the treatment of VHL disease and expanded options for advanced kidney cancer and rare adrenal tumors. It works by targeting a specific molecular pathway — HIF-2α — that drives these particular cancers.

However, it is not a "brain cancer cure." It does not work against glioblastoma or other malignant brain tumors. The CNS tumors it treats (hemangioblastomas) are rare, benign vascular growths specific to VHL disease — a condition affecting roughly 1 in 36,000 people.

Science moves forward through precision, not hype. Belzutifan's real story is remarkable enough without embellishment.

This blog post is grounded in the following key evidence:

The drug's mechanism of action and approved indications come directly from the FDA prescribing information for WELIREG.[1] The VHL disease efficacy data are drawn from the landmark LITESPARK-004 trial published in The New England Journal of Medicine and its 50-month and 5-year follow-up analyses.[2][3][4] The advanced RCC data come from the LITESPARK-005 FDA approval summary.[5] The pheochromocytoma/paraganglioma data are from the LITESPARK-015 trial published in NEJM.[6]

Critically, the claim about "curing brain cancer" is directly refuted by the LITESPARK-001 glioblastoma cohort, presented at ASCO 2024, which showed a 0% objective response rate in 25 patients with recurrent glioblastoma.[7] A JAMA review on glioblastoma further confirmed that glioblastomas are "largely unresponsive to molecularly targeted therapy," explicitly naming belzutifan among drugs that work in other intracranial tumors but not GBM.[8] The NCCN CNS Cancer Guidelines list belzutifan only for VHL-associated hemangioblastomas under "useful in certain circumstances" — not for any malignant brain tumor.[9]

The safety and warnings data are sourced from the FDA label's boxed warning, warnings and precautions, and drug interactions sections.[1]

References

1. WELIREG. Food and Drug Administration. Updated date: 2025-05-14.

2. Belzutifan for Renal Cell Carcinoma in von Hippel–Lindau Disease. Jonasch E, Donskov F, Iliopoulos O, et al. The New England Journal of Medicine. 2021;385(22):2036-2046. doi:10.1056/NEJMoa2103425.

3. Belzutifan for Von Hippel-Lindau Disease-Associated Renal Cell Carcinoma and Other Neoplasms (LITESPARK-004): 50 Months Follow-Up From a Single-Arm, Phase 2 Study. Srinivasan R, Iliopoulos O, Beckermann KE, et al. The Lancet. Oncology. 2025;26(5):571-582. doi:10.1016/S1470-2045(25)00099-3.

4. Hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan in von Hippel-Lindau (VHL) disease–associated neoplasms: 5-year follow-up of the phase 2 LITESPARK-004 study. Narayan V, Jonasch E, Iliopoulos O, et al. Journal of Clinical Oncology. 2025;43(Suppl 16):4507. doi:10.1200/JCO.2025.43.16_suppl.4507.

5. FDA Approval Summary: Belzutifan for Patients With Advanced Renal Cell Carcinoma. Fallah J, Heiss BL, Joeng HK, et al. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research. 2024;30(22):5003-5008. doi:10.1158/1078-0432.CCR-24-1199.

6. Belzutifan for Advanced Pheochromocytoma or Paraganglioma. Jimenez C, Andreassen M, Durand A, et al. The New England Journal of Medicine. 2025;393(20):2012-2022. doi:10.1056/NEJMoa2504964.

7. Phase 1 LITESPARK-001 study of belzutifan in advanced solid tumors: Results of the glioblastoma cohort. Strowd R, Fuente M, Bauer T, et al. Journal of Clinical Oncology. 2024;42(Suppl 16):2054. doi:10.1200/JCO.2024.42.16_suppl.2054.

8. Glioblastoma and Other Primary Brain Malignancies in Adults: A Review. Schaff LR, Mellinghoff IK. JAMA. 2023;329(7):574-587. doi:10.1001/jama.2023.0023.

9. Central Nervous System Cancers. National Comprehensive Cancer Network. Updated 2025-12-05.