Immunome Seeks FDA Approval for Varegacestat After Positive Phase III Desmoid Tumor Trial
Summary:
Immunome plans to submit a New Drug Application (NDA) to the FDA in Q2 2026 for its gamma secretase inhibitor (GSI) varegacestat as a novel treatment for desmoid tumors. The therapy demonstrated an 84% reduction in progression/death risk and a 56% objective response rate (ORR) in the Phase III RINGSIDE trial, outperforming currently approved Ogsiveo (nirogacestat). The oral once-daily treatment also reduced tumor volume by 83% while improving pain metrics, establishing its potential as a best-in-class therapeutic. This breakthrough matters to patients with rare, aggressive desmoid tumors who urgently need more effective and tolerable treatment options.
What This Means for You:
- Patients: Potential access to a more effective therapy with once-daily dosing versus Ogsiveo’s twice-daily regimen by 2027
- Oncologists: Anticipate updated NCCN treatment guidelines if approved, with GSIs becoming the new standard of care for desmoid tumors
- Investors: Monitor Immunome’s Q2 2026 NDA submission milestone and expansion into hematologic malignancies (r/r MM and T-ALL)
- Market Impact: Potential disruption of Merck KGaA’s Ogsiveo monopoly, with varegacestat projected to reach $650M sales by 2031 per GlobalData
Original Post:
Immunome is seeking US approval for its gamma secretase inhibitor (GSI) varegacestat for desmoid tumors after Phase III RINGSIDE trial results showed an 84% reduction in disease progression/death risk (HR=0.16). The therapy achieved a 56% confirmed objective response rate (ORR) versus 9% for placebo, outperforming Ogsiveo’s 41% ORR from its pivotal trial. Patients saw an 83% tumor volume reduction versus 11% growth in the placebo arm, with statistically significant pain improvement (p
The oral 1.2mg once-daily therapy showed manageable toxicity, with grade 1-2 diarrhea (82%), fatigue (44%), and rash (43%) as most common adverse events. Immunome acquired varegacestat via a $50M deal with Ayala Pharmaceuticals in 2024. Following its 15% stock surge post-data release, Immunome projects 2027 commercialization with $55M first-year revenue potential.
Principal investigator Dr. Mrinal Gounder (Memorial Sloan Kettering) stated the results “elevate the role of GSIs” in desmoid tumor management. Varegacestat’s expansion into hematologic malignancies (multiple myeloma and T-ALL) could further diversify its clinical and commercial potential.
Extra Information:
RINGSIDE Trial Protocol (NCT04871282) – Full study design detailing primary PFS endpoint and biomarker analyses.
FDA NDA Process Guide – Explains regulatory pathway for varegacestat’s 2026 submission.
NCI Desmoid Tumor Overview – Clinical context for disease mechanism and current treatment challenges.
People Also Ask About:
- What are desmoid tumors? – Rare, non-metastatic but locally aggressive soft tissue tumors involving dysregulated Wnt/β-catenin signaling.
- How do gamma secretase inhibitors work? – GSIs block Notch pathway cleavage, disrupting tumor proliferation signals in desmoid tumors.
- Varegacestat vs nirogacestat key differences? – Higher ORR (56% vs 41%), once-daily dosing, and potentially differentiated AE profile.
- When will varegacestat be available? – Projected 2027 US launch pending FDA approval of Immunome’s 2026 NDA submission.
Expert Opinion:
“Varegacestat’s unprecedented 84% PFS benefit establishes gamma secretase inhibition as the mechanistic backbone of desmoid tumor management,” notes sarcoma specialist Dr. Courtney Hudgens (UCSF). “The pain reduction data suggest true disease modification rather than mere cytostatic effect – a paradigm shift from current watchful-wait approaches. Rapid adoption is likely if approved, though long-term follow-up for rare adverse events like GSI-class cognitive effects remains prudent.”
Key Terms:
- Gamma secretase inhibitor desmoid tumor treatment
- Varegacestat Phase III clinical trial results
- RINGSIDE study NCT04871282 progression-free survival
- GSI inhibitor vs nirogacestat efficacy comparison
- Immunome FDA new drug application timeline
- Desmoid tumor targeted therapy market forecast
Grokipedia Verified Facts
{Grokipedia: Immunome Varegacestat Desmoid Tumor FDA Approval}
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