Inclusion Criteria
Patients must meet the compassionate access requirements to be eligible for the MAP. These requirements include, but are not limited to:
* Proven, (any body site) or Probable (LTRD) IFI caused by Aspergillus in patients not eligible to receive a treatment with any azole (e.g. due to resistance, intolerance or drug-drug interactions).
* Proven or Probable Lomentospora prolificans\* infections
* Other proven\* mould IFI \*a combination of clinical/host features, radiology and mycology according to the EORTC/MSG Criteria 2019
* Proven CNS Coccidioides in patients with or planned placement of indwelling CNS devices (e.g. reservoirs, shunts, ventriculostomies, or external drainage tubes) or receiving intrathecal (IT) Amphotericin B, when there is failure to previous effective therapies
* Causative organism must be known or predicted to be susceptible to olorofim (susceptibility testing may be required e.g., for Fusarium spp.)
* Evidence of limited treatment options (e.g., evidence for failure/resistance or intolerance to prior therapy Dose limiting drug-drug interactions (DDIs) or the potential for DDIs
* To provide olorofim for patients transitioning from other olorofim interventional trials when those trials close or continued treatment for patients that completed all study visits, for whom on-going therapy has been judged beneficial, for whom on-going therapy has been judged beneficial, or there is a positive clinical risk-benefit to switch to olorofim treatment as demonstrated by an approved compassionate use request.
* The ability to obtain all necessary regulatory approvals for use of an unlicensed drug in the patient's home country
* The ability to ship olorofim in a meaningful timeframe to be able to influence the patient's outcome.
* Prescribing physician has confirmed they have completed relevant training.
* Patients have been fully informed and have given voluntary written informed consent, or whose legally authorized representative(s) have been fully informed and have given voluntary written informed consent, if applicable, and in compliance with local regulations.
In exceptional circumstances and as supported by emerging data, chidren (≥ 6 years) may be considered, assuming all of the above entry criteria are met. Each paediatric case will be considered on a case-by-case basis by the F2G medical team.
Exclusion Criteria:
Compassionate use requests will be submitted via Clinigen Direct and the physician will complete the patient access form (PAF) which documents the criteria which apply to each patient. As part of this assessment the following exclusion criteria apply, but are not limited to:
* Suspected or known hypersensitivity to olorofim.
* Adults with invasive aspergillosis who can receive azole therapy and where they are considered an effective option.
* Patients with confirmed DCM involving extra-pulmonary sites with or without ongoing active disease in lungs, progressive or refractory, even in case of failure to azoles
* Patients with chronic, non-invasive aspergillosis syndromes without evidence of invasive disease
* Patients with 'possible' IFI according to the EORTC/MSG criteria (except for Lomentospora prolificans)
* Patients with underlying pulmonary disease or lung transplant who have evidence for lung colonization with a mould but no corresponding radiological or biopsy evidence for an invasive lung disease.
* Patients receiving treatment limited to supportive care due to predicted short survival time.
* Evidence of hepatic dysfunction with any of the following abnormal laboratory parameters at screening for this MAP:
* Total bilirubin ≥ 2 × upper limit of the normal range (ULN)
* Alanine transaminase or aspartate transaminase ≥ 3 × ULN
* Patients with known cirrhosis or chronic hepatic failure.
* Patients who do not meet the EORTC/MSG criteria (18) for probable L. prolificans or proven IFI e.g., patients with 'possible' IFD or who do not have appropriate host criteria.
Patients that are currently receiving other investigational drugs via a Compassionate use program
Patients receiving Human DHODH inhibitors (eg teriflunomide and leflunomide) and/or cannabinoids.
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