Merck’s Welireg Poised to Dominate a $1.5 Billion Rare Tumor Market: Act Before FDA Approval Unlocks Value

The withdrawal of Lantheus’s Azedra in early 2024 created an immediate and profound void in the treatment of advanced pheochromocytoma and paraganglioma (PPGL), a rare neuroendocrine tumor affecting just 2–8 people per million annually. With no FDA-approved alternatives left on the market, Merck’s (MRK) investigational therapy Welireg (belzutifan) is now positioned to become the sole systemic treatment for this ultra-rare disease. Backed by a May 26, 2025 PDUFA date for its expanded PPGL indication and a $1.5 billion sales forecast by 2030, Welireg represents a rare combination of first-in-class exclusivity, pricing power, and regulatory certainty—making it a compelling buy before its approval unlocks its full market potential.

The PPGL Market Gap: A Void Filled by Welireg’s Novel Mechanism
Azedra’s discontinuation left PPGL patients with few systemic options beyond off-label therapies like chemotherapy or peptide receptor radionuclide therapy (PRRT), which lack FDA approval for this indication. Welireg, however, offers a distinct advantage: it is the first HIF-2α inhibitor explicitly designed to target the hypoxia-inducible factor-2 alpha (HIF-2α) pathway, a key driver of PPGL tumor growth under low-oxygen conditions. This mechanism, validated in prior approvals for von Hippel-Lindau (VHL) disease and certain renal cell carcinomas (RCC), positions Welireg as the only therapy addressing PPGL’s underlying biology.

Sales Trajectory: Rare Disease Pricing Power Meets Unmet Need
With no direct competitors, Welireg’s pricing strategy will be pivotal to its financial success. GlobalData analysts project sales of up to $1.5 billion annually by 2030, driven by rare disease premium pricing and the lack of alternatives. Consider this: Welireg’s existing approvals for VHL and RCC already generated $218 million in global sales in 2023, and its PPGL indication—serving a similarly small but underserved population—could add significantly to this total. In rare disease markets, where patients often pay a premium for life-saving therapies, Welireg’s exclusivity and clinical efficacy could allow Merck to command high prices, particularly for advanced-stage patients with few remaining options.

Regulatory Catalysts: A Near-Term PDUFA Date and Strategic Portfolio Expansion
The May 26 PDUFA date is a critical inflection point. Analysts note that Merck’s HIF-2α pipeline has historically received swift FDA action: its 2021 VHL approval was granted in just 6 months under Priority Review. With the PPGL NDA supported by data from the Phase II LITESPARK-015 trial—which showed promising objective response rates and progression-free survival—the likelihood of approval is high. A positive decision would immediately solidify Welireg’s position as the only approved therapy for advanced PPGL, eliminating competition from withdrawn Azedra and unproven off-label alternatives.

Beyond PPGL, Welireg’s HIF-2α platform creates cross-synergy opportunities. The same pathway drives RCC and VHL, where Welireg is already approved. This “one mechanism, multiple indications” strategy could amplify its sales potential as Merck explores broader applications.

Why Investors Must Act Now
The gap left by Azedra’s withdrawal is not merely a short-term issue—it’s a structural opportunity for Merck to dominate a niche market with high barriers to entry. Competitors would face years of clinical trials to replicate Welireg’s mechanism, while the FDA’s focus on rare disease innovation ensures regulatory support.

With the PDUFA date just 13 days away, the stock could see volatility as investors price in the approval. Historical data shows Merck’s shares often surge after rare disease approvals (see the visual above), and Welireg’s PPGL indication—paired with its existing approvals—could catalyze a sustained upward trend.

Risks? Yes, but Manageable
Welireg’s label includes boxed warnings for severe anemia, hypoxia, and risks to fetal development. However, these side effects are unlikely to derail adoption given the lack of alternatives. Merck’s strong risk management for prior approvals, such as patient support programs and prescriber education, should mitigate concerns.

Conclusion: A Rare Gem at a Crossroads
Merck’s Welireg is not just a single-drug story—it’s a strategic play on exclusivity in rare cancers. With a $1.5 billion market within reach, a near-term regulatory win, and a mechanism that could unlock broader applications, this is a rare chance to invest in a therapy that combines high margins, low competition, and urgent unmet need. Act before May 26—once the FDA’s decision is final, the upside may already be priced in.

Investors should consult with a financial advisor before making investment decisions. This analysis is based on publicly available information and does not constitute personalized investment advice.