F2G, Shionogi's oral anti-fungal scores Phase III success against Gilead's AmBisome in invasive aspergillosis

UK-based F2G Ltd and Japan-based Shionogi & Co., Ltd [reported](https://www.globenewswire.com/news-release/2026/06/18/3313911/0/en/F2G-and-Shionogi-Announce-Positive-Topline-Results-From-Global-Phase-3-OASIS-Study-Evaluating-Oral-Olorofim-Versus-AmBisome-Followed-by-Standard-of-Care-in-Patients-With-Invasive-A.html) that candidate anti-fungal olorofilm produced a Phase III non-inferiority win against Gilead's AmBisome (liposomal amphotericin B) in azole-refractory invasive aspergillosis. The result positions the oral orotomide antifungal as the first candidate in over two decades to offer a mechanistically novel treatment option for one of the most difficult-to-treat fungal infections. The result matters not just for its non-inferiority conclusion, but because it was achieved with a substantially cleaner tolerability profile than the intravenous comparator — significant given that nephrotoxicity frequently limits treatment choices in the targeted patient population. The [OASIS trial](https://clinicaltrials.gov/study/NCT05101187) (NCT05101187) is a global, randomized, non-inferiority study enrolling 225 adults with invasive aspergillosis whose infection was either refractory to or unsuitable for azole therapy. Patients were randomized 2:1 to oral olorofim or liposomal amphotericin B followed by standard of care. The primary endpoint — all-cause mortality at Day 42 — was 23.8% for olorofim versus 24.3% for the comparator arm, a difference of −0.5% (95% CI: −13.1 to 10.8%), comfortably within the pre-specified 20% non-inferiority margin. No new safety signals emerged for olorofim. Drug-related treatment-emergent adverse events occurred in 35.8% of patients on olorofim compared with 63.9% on liposomal amphotericin B, with the gap largely attributable to the higher rate of renal events in the amphotericin arm. **Tolerability as a differentiator** The safety divergence between arms is noteworthy. In immunocompromised patients — the core population for invasive aspergillosis — renal impairment is not merely an adverse event but a clinical constraint that can force dose reductions, treatment interruptions, or switches to less effective regimens. Liposomal amphotericin B, despite its improved renal profile relative to conventional amphotericin B deoxycholate, still carries meaningful nephrotoxicity risk. Olorofim's oral route and distinct mechanism — inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in the fungal pyrimidine biosynthesis pathway that has no equivalent in currently approved antifungals — means it avoids the renal liabilities intrinsic to polyene antifungals. This mechanistic separation also confers activity against azole-resistant *Aspergillus* strains, including those harboring TR34/L98H CYP51A mutations, which are increasingly prevalent globally. The competitive landscape in azole-refractory invasive aspergillosis is sparse. Merck's Cancidas (caspofungin) carries an FDA label explicitly covering the refractory/intolerant population, but as an intravenous echinocandin it is fungistatic rather than fungicidal against *Aspergillus* and requires hospital or infusion center administration. Liposomal amphotericin B, the OASIS comparator, is the most commonly used non-azole option. Cross-trial comparisons carry well-known limitations, but olorofim's oral formulation and mortality outcome numerically equivalent to an IV polyene, combined with a substantially lower adverse event burden, represents a meaningful differentiation in a setting where treatment options have been static for over two decades. **Strategic and regulatory context** F2G holds commercial rights for olorofim in North America and non-Shionogi territories; Shionogi retains Europe and Asia. F2G plans to submit to the US FDA, while Shionogi will file in Europe and Asia. The compound already carries two FDA Breakthrough Therapy Designations — one for invasive mold infections including azole-refractory aspergillosis, and a second for central nervous system coccidioidomycosis — alongside Qualified Infectious Disease Product and orphan drug designations. These designations provide potential priority review and extended exclusivity that strengthen the commercial case for a drug targeting a limited patient population. The broader antifungal pipeline is beginning to show activity. [CorMedix Therapeutics' (Nasdaq: CRMD) rezafungin (Rezzayo)](https://app.allsci.com/news/ASC-NR-0000002343757-1.0-1777289765) recently reported positive Phase III data in prophylaxis for allogeneic stem cell transplant patients, and market analysis suggests the invasive fungal infections space could grow at a compound annual growth rate exceeding 11% in the US through 2034, with Astellas's Cresemba (isavuconazonium sulfate) currently the dominant oral agent for first-line aspergillosis. Olorofim, if approved, would not compete directly with isavuconazole in treatment-naive patients but would occupy the salvage and azole-unsuitable niche — a population with few oral alternatives and high unmet need. Full data from OASIS are expected to be presented at a future medical congress before regulatory submissions proceed. The topline package, combined with existing Phase IIb data published in *The Lancet Infectious Diseases*, provides a substantial evidence base for FDA review. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/olorofim-aspergillosis-trial-beats-ambisome-in)