Gilteritinib Fumarate

100% Overall response rate (ORR) in triple combo study with azacitidine and venetoclax in newly diagnosed AML patients 80% CR and 90% Composite Complete Remissions (CCR); median OS not reached after 9 months and good tolerability 70% of patients derived to Hematopoietic Stem Cell Transplantation (HSCT) 67% CCR at the expansion dose in study evaluating iadademstat plus gilterinib in FLT3-mutated relapsed/refractory AML patients; 47% CR+CRh Treatment was safe and well tolerated MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, December 9th, 2025 - Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and global leader in epigenetics, today reported updated data from clinical studies investigating iadademstat, the Company’s selective LSD1 inhibitor for onco-hematology indications. The results, recently presented at the 67th American Society of Hematology (ASH) Annual Meeting, highlight encouraging efficacy and safety findings from two ongoing studies evaluating iadademstat in combination with standard-of-care regimens in patients with acute myeloid leukemia (AML). ALICE-2 (NCT06357182), a Phase Ib investigator-initiated study sponsored by Oregon Health & Science University (OHSU) in newly diagnosed AML, evaluates treatment with iadademstat in combination with azacitidine and venetoclax, the standard of care in this setting for older or unfit patients. The study’s primary endpoint is the incidence of dose-limiting toxicities (DLTs). Secondary endpoints include efficacy measurements such as composite complete remission (CCR: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete recovery [CRi]), and overall response rate (ORR: CCR + morphologic leukemia free state [MLFS] + partial remission [PR]). Data for 10 patients are reported in the ASH publication. Treatment with iadademstat in combination with azacitidine and venetoclax was safe and well tolerated, with an AE profile similar to other combination treatments in newly diagnosed AML setting. Dose-finding for maximum tolerated dose (MTD) determination is ongoing. The combination treatment resulted in a highly encouraging ORR of 100% and a CCR rate of 90%, with 80% of patients attaining a strict CR. 70% of patients transitioned to allogeneic hematopoietic stem cell transplantation (HSCT). Median overall survival (OS) was not reached, and 6-month OS was 66%. The trial continues to enroll patients at dose level 2 (DL2), with a planned accrual of N=21 MTD-evaluable patients. FRIDA (NCT05546580), a Phase Ib clinical study sponsored by Oryzon, was designed to investigate iadademstat in combination with gilteritinib for the treatment of FLT3-mutant relapsed/refractory AML. The primary endpoints are incidence of treatment emergent adverse events (TEAEs) and determination of the recommended Phase II dose (RP2D). Secondary endpoints include response rates (CR, CRh, CRi, MLFS, CCR), event-free survival (EFS), and overall survival (OS). The ASH communication reports data for 37 patients, with 4 dose level cohorts evaluated in the escalation phase. All doses tested in the escalation phase were safe per DLT criteria. The study is in the expansion phase at one selected pharmacologically active dose , with a total of 17 patients enrolled in the study at this dose level per the ASH poster data cut-off. This dose continues to be well tolerated based on continuous safety monitoring, and has achieved the deepest responses which correlate with the target PK and PD values. Preliminary activity at the dose under expansion shows a 67% CCR (10/15 patients) and a 47% CR+CRh (7/15) in 15 patients evaluable for response, which favorably compares with the results of the ADMIRAL trial (CR+CRh 34%), particularly in light of contemporary practice with many patients (47%) treated at this dose after failing venetoclax, a population with markedly decreased response to gilteritinib monotherapy. Four patients have undergone HSCT. “These impressive preliminary results in first-line AML underscore the potential of iadademstat to deliver meaningful clinical benefit when combined with standard-of-care therapies and to offer patients renewed hope for a truly curative approach,” said Dr. Carlos Buesa, Chief Executive Officer of Oryzon. “The strong outcomes also observed in relapsed/refractory patients across difficult-to-treat AML subsets further highlight that iadademstat-based combinations can achieve robust efficacy while maintaining a manageable safety profile. This demonstration of clinical relevance at ASH reinforces iadademstat’s potential as a best-in-class combination agent and provides a clear path for future clinical development. We continue to explore strategic partnerships to fully unlock the value of iadademstat as a promising oncology–hematology asset.”

- Presentations include pooled post-hoc analysis of the Phase 3 ADMIRAL and COMMODORE data on post-transplant gilteritinib resumption in relapsed or refractory FLT3m+ AML - - Findings from the Phase 3 MORPHO trial in the post-transplant maintenance setting and Phase 1/2 VICEROY trial in newly diagnosed disease highlight how treatment timing, sequencing and combination approaches may influence outcomes - TOKYO, Dec. 5, 2025 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced that new data evaluating XOSPATA™ (gilteritinib) across FMS-like tyrosine kinase 3 mutation-positive (FLT3m+) acute myeloid leukemia (AML), including in relapsed or refractory (R/R), newly diagnosed and post-transplant maintenance settings, will be presented at the upcoming American Society of Hematology (ASH) Annual Meeting taking place from 6-9 December 2025 in Orlando, Fla. Through ongoing research with gilteritinib, Astellas is advancing the science of FLT3m+ AML and generating new evidence across the disease stages, to help improve long-term outcomes for people diagnosed with FLT3m+ AML. Highlights from Astellas at ASH 2025 will include: A pooled post-hoc analysis of the Phase 3 ADMIRAL and COMMODORE trials evaluating gilteritinib in R/R FLT3m+ AML, exploring treatment sequencing and resumption post-transplant to improve outcomes. In collaboration with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) , data from a post-hoc analysis of the Phase 3 MORPHO study examining how time from diagnosis to transplant, use of FLT3 inhibitors before transplant and use of gilteritinib post-transplant influenced outcomes in FLT3m+ AML. Results from the ongoing Phase 1/2 VICEROY study (NCT05520567) investigating triplet combination therapy approach including gilteritinib in newly diagnosed FLT3m+ AML patients ineligible for intensive chemotherapy, focused on safety, efficacy and dosing optimization. Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas "Building on gilteritinib's foundation in treating relapsed or refractory FLT3-mutated AML - one of the most challenging forms of leukemia characterized by high rates of treatment failure and relapse - Astellas is dedicated to advancing research that provides valuable insights to inform clinical practice. This new data exemplifies our 'bench to bedside' approach, translating scientific innovation into VALUE for patients who urgently need new treatment options." Gilteritinib is a FLT3 inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-tyrosine kinase domain (TKD) mutations.1 Gilteritinib is available as XOSPATA® across the world, including in the U.S., Japan, China and multiple European countries for the treatment of adult patients who have relapsed or refractory FLT3m+ AML. The ongoing, randomized, multicenter, open-label, Phase 3 PASHA study (NCT04027309) is evaluating gilteritinib versus midostaurin in combination with induction and consolidation therapy followed by one year of maintenance in patients with newly diagnosed FLT3-mutated AML eligible for intensive chemotherapy. About Gilteritinib Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-TKD mutations.1 It was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global development, commercialization and manufacturing rights to gilteritinib.2 Gilteritinib was evaluated in ADMIRAL (NCT02421939), a Phase 3, open-label, multicenter, randomized clinical trial comparing gilteritinib with prespecified salvage chemotherapy in adult patients with relapsed or refractory FLT3-mutated AML. About Acute Myeloid Leukemia (AML) Acute myeloid leukemia (AML) is an aggressive cancer that affects the bone marrow and blood, and its incidence increases with age.3,4 Of patients newly diagnosed with AML and tested for FLT3 mutations, approximately one-third have an alteration to the FLT3 gene. FLT3-ITD mutations have been associated with worsened disease-free survival and overall survival, and a higher risk of getting the disease more than once. FLT3 mutation status can change over the course of AML treatment, even after relapse.5-8 About Astellas Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. We provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health. Through our research and development programs, we are pioneering new healthcare solutions for diseases with high unmet medical need. Learn more at . Cautionary Notes In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties. Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice. XOSPATA (gilteritinib) U.S. Indication & Important Safety Information Indication XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test. Important Safety Information Contraindications XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials. Warnings and Precautions Differentiation Syndrome (See BOXED WARNING) 3% of 319 patients treated with XOSPATA in the clinical trials experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms and other clinical findings of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation syndrome occurred as early as 1 day and up to 82 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA until signs and symptoms are no longer severe. Posterior Reversible Encephalopathy Syndrome (PRES) 1% of 319 patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES. Prolonged QT Interval XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). 1% of the 317 patients with a post-baseline QTc measurement on treatment with XOSPATA in the clinical trial were found to have a QTc interval greater than 500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration. Pancreatitis 4% of 319 patients treated with XOSPATA in the clinical trials experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis. Embryo-Fetal Toxicity XOSPATA can cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with XOSPATA and for 6 months after the last dose of XOSPATA. Advise males with female partners of reproductive potential to use effective contraception during treatment with XOSPATA and for 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential risk to the fetus. Adverse Reactions Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These were cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase increased (6%) and noninfectious diarrhea (5%). 7% discontinued XOSPATA treatment permanently due to an adverse reaction. The most common (>1%) adverse reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine aminotransferase increased (2%). The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and fatigue/malaise (6%). Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT prolonged (9%), hypersensitivity (8%), pancreatitis (5%), cardiac failure (4%), pericardial effusion (4%), acute febrile neutrophilic dermatosis (3%), differentiation syndrome (3%), pericarditis/myocarditis (2%), large intestine perforation (1%), and posterior reversible encephalopathy syndrome (1%). Lab Abnormalities Shifts to grades 3-4 nonhematologic laboratory abnormalities in XOSPATA treated patients included phosphate decreased (14%), alanine aminotransferase increased (13%), sodium decreased (12%), aspartate aminotransferase increased (10%), calcium decreased (6%), creatine kinase increased (6%), triglycerides increased (6%), creatinine increased (3%), and alkaline phosphatase increased (2%). Drug Interactions Combined P-gp and Strong CYP3A Inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers. Strong CYP3A inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity. Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient. P-gp, BCRP, and OCT1 Substrates Based on in vitro data, gilteritinib is a P-gp, breast cancer resistant protein (BCRP), and organic cation transporter 1 (OCT1) inhibitor. Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates, which may increase the incidence and severity of adverse reactions of these substrates. For P-gp, BCRP, or OCT1 substrates where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such substrate and monitor for adverse reactions as recommended in the respective prescribing information. Specific Populations Lactation Advise women not to breastfeed during treatment with XOSPATA and for 2 months after the last dose. Please see Full Prescribing Information, including BOXED WARNING for additional safety information. 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