SCYNEXIS Halts Phase 3 MARIO Trial, Raising New Questions for Ibrexafungerp’s Growth Path

SCYNEXIS Inc (SCYX) announced an update on their ongoing clinical study.

Study Overview: SCYNEXIS Inc. (SCYX) is running a Phase 3 trial titled “A Phase 3, Multicenter, Prospective, Randomized, Double-blind Study of Two Treatment Regimens for Candidemia and/or Invasive Candidiasis (MARIO).” The study compares two step-down treatment options for serious fungal infections in the blood and organs after initial hospital therapy. Its goal is to see whether the company’s oral drug ibrexafungerp can match or improve on standard care, which could support broader use in a high-need area and inform the long-term commercial outlook for SCYNEXIS.

Intervention/Treatment: All patients first receive an intravenous echinocandin, a common hospital antifungal. They are then switched to one of two oral treatments: ibrexafungerp (SCY-078), the SCYNEXIS drug being tested, or fluconazole, the long-standing standard therapy. The intent is to show that ibrexafungerp can serve as an effective oral follow-on treatment for invasive candidiasis and candidemia, potentially offering doctors a new option beyond fluconazole.

Study Design: This is an interventional Phase 3 trial with patients randomly assigned to one of the two treatment paths. The model is “parallel,” meaning each group receives only one of the two oral options after IV therapy. The trial is double-blind with four-party masking: patients, treating doctors, study investigators, and outcome assessors do not know which oral drug is given. The main purpose is treatment, measuring how well each regimen clears the infection and supports recovery.

Study Timeline: The study was first submitted in December 2021, marking the formal start of regulatory and site setup. It is listed as Phase 3 with a treatment focus, but it has since been labeled “terminated,” signaling that enrollment or follow-up stopped earlier than first planned. The most recent update was filed on December 17, 2025, which tells investors the record was reviewed and adjusted, often to align with updated strategy, safety, or operational decisions. No primary or final results have yet been posted on the registry.

Market Implications: Termination of a late-stage trial in a key indication usually creates uncertainty around a drug’s path to market and can weigh on short-term sentiment toward SCYNEXIS shares. Investors may worry about safety, efficacy, enrollment issues, or shifting priorities, even if full details are not yet public. At the same time, ibrexafungerp already has a presence in fungal disease, and management may re-focus on other indications or partnership strategies. Competitors in invasive fungal infections, including makers of echinocandins and azoles, could benefit at the margin if ibrexafungerp’s role in this setting becomes narrower. For now, the update mainly reinforces the need for investors to watch future disclosures from SCYNEXIS for clarity on clinical strategy, regulatory plans, and any read-through to revenue expectations.

The MARIO study record has been recently updated on ClinicalTrials.gov, and further details are available on the ClinicalTrials portal.

To learn more about SCYX’s potential, visit the SCYNEXIS Inc drug pipeline page.