Immunome's Competitive Edge in the Desmoid Tumor Market

The desmoid tumor market is undergoing a transformative phase, driven by the emergence of targeted therapies that address the unmet needs of patients with this rare and aggressive disease. Among the key players vying for dominance, Immunome, Inc. (IMNM) has positioned itself as a formidable contender with its gamma secretase inhibitor, varegacestat (IPI-549). This article evaluates Immunome's clinical and commercial potential against established therapies like Merck KGaA's OGSIVEO (nirogacestat) and SpringWorks Therapeutics' mirdametinib, drawing on recent trial data, regulatory developments, and market dynamics.

Clinical Pipeline: A Race for Efficacy and Safety

Immunome's varegacestat has demonstrated robust early-phase results in desmoid tumors. In Phase 2 trials, , , indicating reduced cellularity according to clinical data. These outcomes, coupled with a generally well-tolerated safety profile, have propelled varegacestat into Phase 3 trials under the RINGSIDE Part B study. Topline results from this pivotal trial are expected by December 15, 2025, and will serve as a critical inflection point for Immunome's prospects.

In contrast, SpringWorks' OGSIVEO (nirogacestat), a gamma secretase inhibitor approved in 2023, has established itself as the first FDA- and EU-approved therapy for progressing desmoid tumors. Based on the Phase 3 DeFi trial, , alongside improvements in progression-free survival and patient-reported outcomes. Long-term follow-up data from the DeFi trial, published in 2025, . However, OGSIVEO's commercial success- in net product revenue for Q3 2024-comes with challenges, including the high cost of targeted therapies and the need for long-term patient management.

SpringWorks' mirdametinib, a approved for (NF1), has not yet secured regulatory approval for desmoid tumors. While mirdametinib showed a 41% ORR in adults and 52% in children for NF1-related plexiform neurofibromas, its application to desmoid tumors remains unproven. This highlights a key differentiator for Immunome: varegacestat's direct focus on desmoid tumors, whereas competitors like mirdametinib are repurposing assets from other indications.

: Growth, Competition, and Pricing Pressures

, . North America dominates the market, according to market analysis, driven by advanced healthcare infrastructure and early adoption of novel therapies. However, high treatment costs and limited access to FDA-approved options remain barriers, particularly in low-income regions.

OGSIVEO's approval has set a benchmark for efficacy in desmoid tumors, but its commercial success hinges on pricing and reimbursement strategies. At , OGSIVEO has already captured a significant market share, though its long-term sustainability will depend on Immunome's ability to demonstrate superior outcomes or cost-effectiveness. For Immunome, the RINGSIDE Part B trial represents a pivotal opportunity to differentiate varegacestat through higher ORRs or improved safety profiles. If the Phase 3 results replicate Phase 2 efficacy, the drug could challenge OGSIVEO's market leadership, particularly if priced competitively.

Strategic Positioning and Risk Factors

Immunome's pipeline extends beyond varegacestat, with its proprietary TOP1 inhibitor ADC payload, HC74, showing promise in B-cell lymphoma patients. This diversification mitigates reliance on a single asset but also spreads resources thin. Conversely, SpringWorks' dual focus on OGSIVEO and mirdametinib provides a broader revenue stream, though mirdametinib's desmoid tumor application remains unvalidated.

A critical risk for Immunome lies in the potential for adverse Phase 3 results. While Phase 2 data are encouraging, the leap to pivotal trials often reveals unforeseen challenges. Additionally, regulatory hurdles-such as the need for a robust safety profile-could delay approval. However, the absence of a second FDA-approved therapy for desmoid tumors creates a vacuum that Immunome could exploit if varegacestat meets its endpoints.

Conclusion: A High-Stakes Pivotal Moment

The desmoid tumor market is poised for significant growth, but success will hinge on clinical differentiation and commercial execution. Immunome's varegacestat has the potential to disrupt the status quo, provided the RINGSIDE Part B trial delivers on its promise. While OGSIVEO has established a foothold, its dominance is not unassailable. If varegacestat demonstrates superior efficacy or a more favorable safety profile, Immunome could emerge as a key player in this niche but high-impact market. Investors, however, must remain cautious until the December 2025 data release, which will determine whether Immunome's gamble on varegacestat pays off.