- Data are based mostly on evaluation of the primary 100 sufferers from an ongoing Phase 2b examine of sufferers who’ve restricted or no remedy choices for invasive fungal infections
- Overall, a 44% response price, outlined as full or partial response, was seen throughout fungi at day 42, the first endpoint
- All-cause mortality (ACM) at day 42 and day 84 had been 15% and 20%, respectively
MANCHESTER, United Kingdom, Oct. 21, 2022 (GLOBE NEWSWIRE) — F2G Ltd, a clinical-stage biopharmaceutical firm targeted on the invention and growth of novel therapies to deal with life-threatening uncommon fungal infections with a excessive unmet medical want, in the present day introduced at IDWeek 2022 optimistic knowledge from the primary 100 sufferers who accomplished examine remedy in its ongoing Phase 2b open-label examine (Study 32, NCT03583164) of oral olorofim as a remedy for invasive fungal infections.
“Invasive fungal infections are a major problem, particularly among immunosuppressed patients. Patients may be refractory or unable to tolerate existing antifungal treatments and, in some cases, fungi are resistant to available therapies, underscoring the need for new and effective antifungal treatments. Approximately 75% of patients in this analysis had moderate to high levels of immunosuppression, with about half suffering from fungal infections due to Aspergillus. Other causes of infection included filamentous fungi such as Lomentospora prolificans and dimorphic fungi such as Coccidioides species (which causes Valley Fever),” mentioned John H. Rex, MD, chief medical officer of F2G. “We are encouraged by these results because they demonstrate a positive risk-benefit profile for olorofim as an oral therapeutic option for the treatment of serious or life-threatening invasive fungal infections in patients who have limited or no treatment options.”
Key findings:
- Data got here from 100 sufferers with confirmed invasive fungal an infection or possible pulmonary invasive aspergillosis (IA). Causative organisms included Aspergillus spp., Lomentospora prolificans, Scedosporium spp., Scopulariopsis spp., Coccidioides spp., and different olorofim-susceptible fungi. Patients had restricted various remedy choices; causes for this included failure of accessible remedy, resistance of infecting isolate to all licensed brokers, intolerance to obtainable remedy, incapacity to handle drug-drug interactions, and/or incapacity to supply therapeutic drug ranges.
- The median dosing length in the principle part of the examine was 84 days; sufferers (n=42) who entered the extension part of the examine had been dosed for a median of 308 days.
- Olorofim demonstrated a optimistic risk-benefit profile
- At day 42, 44% of sufferers had a whole or partial response to remedy
- With steady response price included, the general response price was 69%
- All-cause mortality (ACM) at day 42 and day 84 had been 15% and 20%, respectively.
- Olorofim was usually properly tolerated
- The solely vital critical opposed occasion was drug-induced liver harm (DILI) which was regarded as presumably associated to olorofim in 8 (8%) examine sufferers; solely 2 (2%) sufferers required discontinuation of olorofim as a result of DILI.
- Other non-serious opposed occasions noticed included diarrhea, nausea, and vomiting.
“Mortality remains unacceptably high in patients with severe and life-threatening fungal infections being treated with currently available therapies. Developing new antifungals, like olorofim, that can meet this clear unmet need is a priority. With its novel mechanism of action, olorofim has shown activity against a wide range of fungi, including some for which there is currently no approved treatment. These data provide evidence that we are on the path to meeting this need in patients currently with limited or no treatment options,” added Johan Maertens, MD, PhD, Professor of Hematology at University Hospitals Leuven (Belgium) and first creator for Study 32.
Olorofim is the one antifungal remedy to be awarded Breakthrough Therapy Designation by the US Food and Drug Administration (FDA). Olorofim works via a novel mechanism of motion, completely different from present lessons of antifungals, exerting fungicidal exercise via inhibition of the enzyme dihydroorotate dehydrogenase (DHODH) within the pyrimidine synthesis pathway. It is energetic in vitro in opposition to Aspergillus spp. (together with azole-resistant and cryptic species), uncommon molds (e.g., Lomentospora prolificans, Scopulariopsis), and dimorphic fungi (e.g., Coccidioides spp.).
About Study 32
Study 32 is an ongoing multicenter, open-label, Phase 2b examine to judge the protection and efficacy of olorofim (previously F901318) in sufferers ≥ 18 years of age with possible pulmonary invasive aspergillosis or confirmed invasive fungal infections as a result of Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and different resistant fungi with restricted or no remedy choices.
Enrolled sufferers obtain an preliminary loading dose of 150 mg BID (twice a day) of oral olorofim on day one, and subsequent oral doses of 90 mg BID for as much as 90 days. Patients are adopted for an additional 4 weeks after finish of remedy, whereas some obtain prolonged remedy for so long as thought helpful. For extra info on Study 32, go to ClinicalTrials.gov (NCT03583164).
About Olorofim
Olorofim (previously, F901318) is F2G’s main candidate from the orotomide class and is at present being investigated in a Phase 2b open-label examine in sufferers who’ve restricted remedy choices for difficult-to-treat invasive, uncommon fungal mildew infections similar to azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and different uncommon mildew infections. F2G has initiated a world Phase 3 trial (“OASIS”) to check remedy with olorofim versus AmBisome® adopted by customary of care (SOC) in sufferers with decrease respiratory tract invasive fungal illness attributable to confirmed or possible an infection with Aspergillus species (NCT05101187). Olorofim has acquired orphan drug standing from the European Medicines Agency for the remedy of invasive aspergillosis and invasive scedosporiosis. Olorofim has additionally acquired orphan drug standing from the FDA for the remedy of coccidioidomycosis, scedosporiosis, and invasive aspergillosis. Olorofim has been granted Qualified Infectious Disease Product (QIDP) designation for invasive aspergillosis, invasive scedosporiosis, invasive lomentosporiosis, coccidioidomycosis, invasive illness as a result of Scopulariopsis species, and invasive fusariosis. Olorofim has acquired Breakthrough Therapy Designation for each “treatment of invasive mold infections in patients with limited or no treatment options, including aspergillosis refractory or intolerant to currently available therapy, and infections due to Lomentospora prolificans, Scedosporium, and Scopulariopsis species” and “treatment of Central Nervous System (CNS) coccidioidomycosis refractory or otherwise unable to be treated with standard of care therapy.” The scientific info mentioned on this information launch associated to olorofim is preliminary and investigative. Olorofim shouldn’t be accredited by the U.S. Food and Drug Administration, and no conclusions can or needs to be drawn relating to its security or efficacy.
About F2G
F2G is a biotech firm with operations within the UK, US, and Austria targeted on the invention and growth of novel therapies to deal with probably life-threatening invasive fungal infections. F2G has found and developed a very new class of antifungal brokers referred to as the orotomides which selectively goal a key enzyme within the de novo pyrimidine biosynthesis pathway. This is a very completely different mechanism from that of the at present marketed antifungal brokers and provides the orotomides fungicidal exercise in opposition to a broad vary of uncommon and resistant fungal mildew infections. For extra info, please go to: www.f2g.com
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