Shionogi BV

This was announced yesterday (April 12) by the executive officer, Isao Teshirogi, of Shionogi BV, the European subsidiary of Shionogi & Co., Ltd. Pete Richardson, managing director, UK Fragile X Society, said: “FXS is a frequently misunderstood condition and too often individuals and families struggle to gain access to the support they need from health and social care systems. Individuals with FXS can face wide-ranging challenges both from the condition itself, where there is a range of symptoms which can limit their ability to independently care for themselves or communicate with others, as well as a lack of awareness and understanding by healthcare professionals and the broader public.” He added that this Orphan Medicinal Product designation offers potential hope for a new treatment option which, although not necessarily suitable for all those with FXS, could improve the wellbeing of individuals and families living with the condition. Orphan Medicinal Product designation is granted to treatments that potentially offer significant benefit for life-threatening or chronically debilitating conditions with a prevalence of fewer than five in 10,000 individuals in Europe. While there are more than 30 million people in Europe impacted by rare diseases, they are often denied diagnosis, treatment, and the benefits of research, making this designation a significant milestone for disorders like FXS. FXS is a neurodevelopmental disorder that can cause a range of cognitive, behavioral, and physical challenges, including those that persist across many aspects of daily life, such as an individual’s ability to care for themselves and communicate with others. Despite the sometimes-profound impact of FXS on individuals, there are no pharmacological treatments specifically approved by the European Medicines Agency for the treatment of FXS, highlighting the currently unmet need for innovative medicines for this community. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Juan-Carlos Gomez, chief medical officer, at Shionogi said: “We are committed to bringing to market new and innovative medicines that improve lives and create solutions for rare pediatric and orphan diseases that are often overlooked. We welcome this regulatory designation in Europe, which recognizes the potential clinical benefit of zatolmilast. This is a significant step forward in helping to bring this medicine to those who may benefit from it.” Shionogi is dedicated to the research and development of innovative medicines that address unmet medical needs, particularly for patients who currently have limited treatment options. In alignment with this global vision, Shionogi acquired Tetra Therapeutics, the developer of zatolmilast, in 2020. Zatolmilast, if approved, aims to become the first cognitive treatment developed specifically for this rare genetic disorder. FXS is known to have a greater effect on males than females because the mutation of the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene is carried on the X chromosome. An important clinical feature abnormality associated with FXS is global developmental delay and intellectual disability. Other common symptoms of FXS include behavioral problems, attention deficits, and anxiety. FXS can cause challenges across many aspects of daily life, such as an individual’s ability to care for themselves and communicate with others.

An overall success rate of 28.7% was seen at day 42, the primary endpoint, and 27.2% at day 84, as determined by a data review committee (DRC) using the EORTC-MSG criteriaThe success rate rose to 75.2% at day 42 and 63.4% at day 84 when stable disease was counted as successAll-cause mortality (ACM) at day 42 and day 84 was 11.4% and 15.8%, respectively MANCHESTER, United Kingdom and OSAKA, Japan, Oct. 21, 2023 (GLOBE NEWSWIRE) -- F2G Ltd. and Shionogi & Co., Ltd., today announced full results from the pivotal Phase 2b open-label study (Study 32, NCT03583164) of olorofim in patients with proven invasive fungal infections (IFI) or probable pulmonary invasive aspergillosis and limited or no treatment options. These findings were submitted as a late breaking abstract and exceptionally accepted for an oral presentation during the 11th Congress on Trends in Medical Mycology (TIMM) 2023 held in Athens, Greece, from 20-23 October 2023. Altogether, ten olorofim-related abstracts from F2G and independent experts were accepted for presentation at TIMM, one of the largest global meetings in which scientists and clinicians from all over the world present their latest advances and research findings in medical mycology. “We are excited about this data as it builds on the previous findings we announced at IDWeek 2022 demonstrating that olorofim has the potential to address a high unmet need in treating infections due to moulds including species considered resistant to all approved antifungals,” said John H. Rex, MD, Chief Medical Officer of F2G. Juan Carlos Gomez, Chief Medical Officer of Shionogi & Co., Ltd. added, “In 2022, the World Health Organization published the fungal priority pathogens list, recognizing the burden of invasive fungal infections and highlighting the need for more antifungal agents to overcome increasing antifungal resistance and rare fungal pathogens. We are encouraged by these data because they demonstrate olorofim was generally well tolerated and has the potential to treat patients with life-threatening fungal infections.” Johan Maertens, MD, PhD, Professor of Hematology at University Hospitals Leuven (Belgium) who presented the data for Study 32, added, “There is a critical need for novel antifungal therapies because lifesaving medical interventions such as organ transplants and cancer therapies, along with an ageing population, have created an increase in immunocompromised people who are at risk of invasive fungal infections from pathogens, and many of these are becoming harder to treat. I am optimistic about olorofim’s potential to address this need.” Key findings: Data came from a Phase 2b open-label study of oral olorofim in 203 patients with limited treatment options for proven IFI or probable pulmonary invasive aspergillosis (IA). 202 patients had IFI meeting the modified ITT (mITT) criteria for analysisCausative organisms included Aspergillus species (101, including 22 cases with azole-resistant strains), Lomentospora prolificans (26), Scedosporium spp. (22), Coccidioides spp. (41), Scopulariopsis spp (6) and other fungi (8).All patients had limited alternative treatment options including failure of available therapy, resistance of infecting isolate to all licensed agents, intolerance to available therapy, inability to manage drug-drug interactions, and/or inability to produce therapeutic drug levels.Treatment was for up to 84 days +/- 7 days with extended therapy permitted when clinically indicated. The median dosing duration in the main phase of the study was 84 days. When including extended therapy, the median treatment duration was 308 days.Olorofim demonstrated an acceptable benefit-risk profile in a well-defined population of patients with limited or no treatment options for infections due to moulds including species considered resistant to all approved antifungals. The overall success rate at day 42 (primary endpoint), as determined by an independent DRC applying the EORTC-MSG criteria1, was 28.7% at day 42 and 27.2% at day 84.The overall success in patients with an IFI other than coccidioidomycosis (n = 161), was 36.0% at day 42 and 34.2% at day 84.For patients with coccidioidomycosis (n = 41, none of whom achieved overall success due to inability to prove fungal eradication in the 84-day study period), benefit (symptoms/signs) was obtained in 31 patients (75.6%, CI 59.7,87.6) achieving complete or partial clinical response at day 42, and 30 patients (73.2%, CI 57.1, 85.8) at day 84.When considering stable disease as a successful clinical response, the rates of successful outcome for the whole population at day 42 and day 84 rose to 75.2% and 63.4%, respectively. ACM at day 42 and day 84 was 11.4% and 15.8%, respectively (IA: 17.8% and 25.7%; non-IA infections 5.0% and 5.9%, respectively).Olorofim was generally well-tolerated, even with dosing >2 year in extension therapy. Changes in liver biochemistry that were deemed at least possibly due to olorofim were seen in 9.9% of study subjects overall (main phase + extended therapy) and were managed by dose reduction/pause.Changes in the liver biochemistry led to permanent discontinuation in 2.5%.Gastrointestinal intolerance to olorofim, generally self-limiting, was noted in 9.9%. F2G and Shionogi & Co., Ltd. are collaborating to develop and commercialise olorofim, bringing the novel antifungal therapy to patients with invasive fungal infections. F2G has commercial responsibility for olorofim in North America, and Shionogi has commercial responsibility for olorofim in Europe and Asia Pacific. F2G and Shionogi are currently enrolling patients with invasive aspergillosis in a global Phase 3 study (OASIS) to compare treatment with olorofim versus AmBisome® followed by standard of care (NCT05101187). About Study 32 Study 32 was a multicenter, open-label, Phase 2b study to evaluate the safety and efficacy of olorofim (formerly F901318) in patients ≥ 18 years of age with probable pulmonary invasive aspergillosis or proven invasive fungal infections due to Lomentospora prolificans, Scedosporium spp., Aspergillus spp., and other resistant fungi with limited or no treatment options. It enrolled patients between June 2018 and September 2022. Enrolled patients received an initial loading dose of 150 mg BID (twice a day) of oral olorofim on day one, and subsequent oral doses of 90 mg BID for up to 90 days. Patients were followed for another four weeks after the end of treatment, while some received extended therapy for as long as thought clinically beneficial. For more information on Study 32, visit ClinicalTrials.gov (NCT03583164). About Olorofim Olorofim (formerly, F901318) is F2G’s leading candidate from the orotomide class. A Phase 2b single-arm open-label study in patients who have limited treatment options for difficult-to-treat invasive fungal infections due to mould such as azole-resistant aspergillosis, scedosporiosis, lomentosporiosis, and other rare mould infections has completed enrollment. To expand on the studied patient population, F2G has initiated a global Phase 3 trial (“OASIS”) to compare treatment with olorofim versus AmBisome® followed by standard of care (SOC) in patients with proven or probable invasive fungal infection due to Aspergillus species (NCT05101187). Olorofim has received orphan drug designation from the FDA for the treatment of coccidioidomycosis, scedosporiosis (including lomentosporiosis), invasive Scopulariopsis, and invasive aspergillosis. Olorofim has also received orphan drug designation from the European Medicines Agency (EMA) for the treatment of invasive aspergillosis, invasive scedosporiosis (including lomentosporiosis), and invasive Scopulariopsis. Olorofim has been granted Qualified Infectious Disease Product (QIDP) designation for invasive aspergillosis, invasive scedosporiosis, invasive lomentosporiosis, coccidioidomycosis, invasive disease due to Scopulariopsis species, and invasive fusariosis. Olorofim has received FDA Breakthrough Therapy Designation for both “treatment of invasive fungal 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.” Olorofim is not approved by the FDA or any other regulatory agency. Invasive fungal infections cause substantial morbidity and mortality, particularly among immunosuppressed patients, and can cause significant morbidity in otherwise healthy individuals when they get into soft tissues, bones and joints, requiring both antifungal therapy and major surgical interventions. Effective antifungal therapies do not currently exist for some of these fungi. Even when therapies exist, some patients with invasive infections may be refractory or unable to tolerate existing antifungal treatments, thus underscoring the need for new and effective treatments. About F2G F2G is a biotech company with operations in the UK, US, and Austria focused on the discovery and development of novel therapies to treat potentially life-threatening invasive fungal infections. F2G has discovered and developed a completely new class of antifungal agents called the orotomides which selectively target a key enzyme in the de novo pyrimidine biosynthesis pathway. This is a completely different mechanism from that of the currently marketed antifungal agents and gives the orotomides fungicidal activity against a broad range of rare and resistant fungal mold infections. For more information, please visit: www.f2g.com About Shionogi Shionogi & Co., Ltd. is a 145-year-old global, research driven pharmaceutical company headquartered in Osaka, Japan, that is dedicated to bringing benefits to patients based on its corporate philosophy of “supplying the best possible medicine to protect the health and wellbeing of the patients we serve.” The company currently markets products in several therapeutic areas including anti-infectives, pain and CNS disorders.Shionogi’s research and development currently target two therapeutic areas: infectious diseases, and pain/CNS disorders. For more information on Shionogi & Co., Ltd., please visit http://www.shionogi.co.jp/en/. Shionogi B.V. is the European headquarters of Shionogi & Co., Ltd. For more information on Shionogi B.V., please visit www.shionogi.eu. Forward-Looking Statements This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also, for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise. Media Contact:Gloria GasaaturaLifeSci Communications+1 646 970 4688ggasaatura@lifescicomms.com SHIONOGI Website Inquiry Form https://www.shionogi.com/global/en/contact.html.EU Media: pressoffice:shionogi.eu _____________________________________1 Segal BH, Herbrecht R, Stevens DA, Ostrosky-Zeichner L, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clin Infect Dis. 2008 Sep 1;47(5):674-83. doi: 10.1086/590566. PMID: 18637757; PMCID: PMC2671230.