The U.S. Food and Drug Administration (FDA) has expanded the approval of Merck's Welireg (belzutifan) to include treatment of patients with renal cell carcinoma (RCC) who have progressed following immunotherapy and targeted therapy, offering a new option for patients with limited alternatives.
The approval comes just months after Merck reported positive interim results from a pivotal trial in August. Welireg, which works by inhibiting hypoxia-inducible factor-2 alpha (HIF-2α), demonstrated a 25% reduction in the risk of disease progression or death compared to everolimus, an established treatment option.
Clinical Trial Results
The FDA based its decision on data showing Welireg shrank or eliminated tumors in 22% of treated patients. The drug demonstrated a median progression-free survival of 5.6 months, comparable to everolimus, with the 25% relative risk reduction resulting from delayed progression in patients who surpassed this median timepoint.
However, some oncologists have questioned the drug's value, as it has not yet demonstrated an overall survival benefit. The clinical significance of the progression-free survival advantage remains a topic of discussion among specialists.
"The approval of Welireg represents an important advancement for patients with renal cell carcinoma who have exhausted standard treatment options," said a Merck spokesperson. "We are committed to continuing research to fully understand the potential benefits of this novel mechanism of action."
Novel Mechanism of Action
Welireg stands out as a first-in-class HIF-2α inhibitor, blocking the production of a protein implicated in cancer growth. This mechanism differs from existing kidney cancer treatments, potentially offering benefits to patients who have developed resistance to other therapies.
The drug was first approved in 2021 for cancers associated with von Hippel-Lindau disease, a rare genetic disorder. This new indication significantly expands the potential patient population who may benefit from the treatment.
Commercial Implications
Merck acquired Welireg through its $1 billion purchase of biotechnology company Peloton Therapeutics in 2019. The company views the drug as a potential blockbuster and future growth driver, though sales have been modest thus far, generating approximately $146 million through the first nine months of 2023.
The expanded approval into the broader kidney cancer market could substantially increase these figures. Renal cell carcinoma represents a much larger commercial opportunity than the rare condition for which Welireg was initially approved.
Treatment Landscape for Renal Cell Carcinoma
Renal cell carcinoma is the most common type of kidney cancer, with approximately 79,000 new cases diagnosed annually in the United States. Despite advances in treatment options, patients who progress after immunotherapy and targeted agents have limited effective options.
The standard treatment pathway typically involves initial treatment with immunotherapies like Merck's own Keytruda (pembrolizumab), followed by targeted therapies. Welireg now offers an additional line of defense for patients whose disease continues to progress.
Safety Profile and Administration
Like many cancer therapies, Welireg comes with potential side effects. Common adverse reactions observed in clinical trials included anemia, fatigue, and nausea. The drug's prescribing information includes specific monitoring recommendations to manage these effects.
Welireg is administered orally, which may offer convenience advantages for patients compared to some alternative treatments that require intravenous administration.
Future Directions
Merck continues to study Welireg in additional clinical settings, exploring its potential in other cancer types and earlier treatment lines. The company is also investigating combination approaches that might enhance efficacy.
As longer-term data matures, researchers will be watching closely to determine whether the progression-free survival benefit eventually translates to an overall survival advantage, which would strengthen the drug's clinical value proposition.
