Jazz Pharmaceuticals Plc

Modeyso, the first treatment option for this ultra-rare and aggressive brain tumor, is commercially available in the United States For U.S. media and investors only DUBLIN , Sept. 9, 2025 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that Modeyso™ (dordaviprone) is recommended by the National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 2A single-agent treatment option for pediatric and adult patients with recurrent or progressive diffuse high-grade glioma harboring an H3 K27M mutation. Modeyso was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on August 6, 2025 for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in the Phase 3 ACTION confirmatory trial.1 "The rapid addition of Modeyso to the NCCN Guidelines® – in both the Pediatric Central Nervous System Cancers and Central Nervous System Cancers guidelines – reflects the urgency of the unmet need that patients are faced with when diagnosed with this devastating and aggressive brain tumor," said Kelvin Tan, MB BCh, MRCPCH, chief medical affairs officer of Jazz Pharmaceuticals . "We are proud to bring Modeyso to patients in the U.S. as the first treatment option for recurrent H3 K27M-mutant diffuse midline glioma, representing a meaningful shift in the treatment landscape for patients and their families." The NCCN Guidelines® play a pivotal role in decision-making processes for individuals involved in cancer care all over the world, including physicians, nurses, pharmacists, payers, and patients and their families. The guidelines present expert recommendations for cancer screening, diagnosis and treatment, as well as cancer care options, and are utilized in cancer treatment decision-making to drive positive patient outcomes. NCCN is a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research and education. NCCN is dedicated to defining and advancing effective, equitable, accessible and quality cancer care and prevention so all people can live better lives. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. The FDA approval of Modeyso was based on an integrated efficacy analysis of 50 patients with recurrent H3 K27M-mutant diffuse midline glioma, selected from five open-label clinical studies based on pre-specified eligibility criteria. The overall response rate (ORR), as assessed by blinded independent central review (BICR) using Response Assessment in Neuro-Oncology (RANO) 2.0 criteria, was 22% (95% CI: 12 to 36), with an additional responder identified by integrated RANO 2.0. Among responders, the median duration of response was 10.3 months (95% CI: 7.3 to 15.2), with 73% maintaining their response for at least six months and 27% for at least 12 months.1 The safety of Modeyso was evaluated in 376 adult and pediatric patients with glioma across four open-label clinical studies. Serious adverse reactions occurred in 33% of patients. Serious adverse reactions reported in more than 2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%) and muscular weakness (2.1%). The most common adverse reactions in patients who received Modeyso (≥20%) were fatigue, headache, vomiting, nausea and musculoskeletal pain.1 See additional safety information below and full prescribing information: https://pp.jazzpharma.com/pi/modeyso.en.USPI.pdf About H3 K27M-Mutant Diffuse Midline Glioma H3 K27M-mutant diffuse midline glioma is a rare and highly aggressive brain tumor that primarily affects the midline structures of the brain and spinal cord.2,3 It is characterized by a specific genetic mutation (H3 K27M) that disrupts epigenetic regulation and drives tumor growth.4 Most commonly diagnosed in children and young adults, patients with this type of glioma often face an extremely poor prognosis, with limited therapeutic options and very low survival rates following recurrence.5 Median survival is approximately one year from diagnosis and less than six months after disease progression following frontline therapy.5 About Modeyso™ (dordaviprone) Modeyso (dordaviprone) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma harboring an H3 K27M mutation with progressive disease following prior therapy.1 Modeyso is an orally administered small molecule given once weekly. Modeyso is a protease activator of the mitochondrial caseinolytic protease P (ClpP) and also inhibits dopamine D2 receptor (DRD2). In vitro, dordaviprone activates the integrated stress response, induces apoptosis and alters mitochondrial metabolism, leading to restored histone H3 K27 trimethylation in H3 K27M-mutant diffuse glioma.1 Modeyso received accelerated approval based on a pre-specified integrated efficacy analysis of 50 adult and pediatric patients with recurrent H3 K27M-mutant diffuse midline glioma enrolled across five open-label clinical studies (ONC006, ONC013, ONC014, ONC016 and ONC018). Continued approval may be contingent upon verification and description of clinical benefit in the ongoing Phase 3 ACTION trial (NCT05580562), which is evaluating the safety and clinical benefit of Modeyso in newly diagnosed patients with H3 K27M-mutant diffuse glioma following radiotherapy.4 Modeyso was developed by Chimerix prior to its acquisition by Jazz Pharmaceuticals in April 2025 . Modeyso (dordaviprone) is not approved anywhere else in the world. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS HypersensitivityMODEYSO can cause severe hypersensitivity reactions. In the pooled safety population, Grade 3 hypersensitivity reactions occurred in 0.3% of patients receiving MODEYSO. Signs and symptoms of hypersensitivity may include rash, hives, fever, low blood pressure, wheezing, or swelling of the face or throat. Inform patients about the signs and symptoms of hypersensitivity reactions and instruct them to seek immediate medical attention if symptoms occur. If clinically significant hypersensitivity or anaphylaxis occur, immediately interrupt MODEYSO and initiate appropriate medical treatment and supportive care. Based on the severity of the adverse reaction, temporarily interrupt or permanently discontinue MODEYSO. QTc Interval ProlongationMODEYSO causes concentration-dependent QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g. torsades de pointes) or sudden death. In patients who received MODEYSO and underwent at least one post baseline ECG, QTcF increase of >60 msec compared to baseline and QTcF >500 msec occurred in 6% and 1.2% of patients, respectively. Monitor ECGs and electrolytes prior to initiation and periodically during treatment, as clinically indicated. Increase the frequency of monitoring in patients with congenital long QT syndrome, existing QTc prolongation, a history of ventricular arrhythmias, electrolyte abnormalities, heart failure, or who are taking strong or moderate CYP3A4 inhibitors. Avoid concomitant use with other agents known to prolong the QT interval. If concomitant use cannot be avoided, increase the frequency of monitoring and separate administration of MODEYSO and QT-prolonging product. Interrupt or reduce the dose of MODEYSO in patients who develop QT prolongation; permanently discontinue in patients with signs of life-threatening arrhythmias. Embryo-Fetal Toxicity MODEYSO can cause fetal harm when administered to a pregnant woman.Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MODEYSO and for 1 month after the last dose ADVERSE REACTIONSSerious adverse reactions occurred in 33% of the 376 patients who received MODEYSO. Serious adverse reactions in >2% of patients included hydrocephalus (5%), vomiting (4.3%), headache (3.2%), seizure (2.4%), and muscular weakness (2.1%). Fatal adverse reactions occurred in 1% of patients who received MODEYSO, including cardiac arrest (0.5%), intracranial hemorrhage (0.3%), and encephalopathy (0.3%). The most common adverse reactions (≥20%) reported in clinical trials with MODEYSO were fatigue (34%), headache (32%), vomiting (24%), nausea (24%), and musculoskeletal pain (20%). The most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (7%), decreased calcium (2.7%), and increased alanine aminotransferase (2.4%). DRUG INTERACTIONS Strong and Moderate CYP3A4 Inhibitors Avoid concomitant use of MODEYSO with strong and moderate CYP3A4 inhibitors. If concomitant use cannot be avoided, reduce the MODEYSO dose as recommended and monitor for toxicity. Strong and Moderate CYP3A4 Inducers Avoid concomitant use of strong and moderate CYP3A4 inducers with MODEYSO. USE IN SPECIFIC POPULATIONS LactationThere are no data on the presence of MODEYSO in human milk because of the potential for serious adverse reactions from MODEYSO in breastfed children, advise women not to breastfeed during treatment with MODEYSO and for 1 week after the last dose. Pediatric UseThe safety and effectiveness of MODEYSO have not been established in patients less than 1 year of age. Dosing has not been established for patients weighing less than 22 pounds (10 kg). Please refer to the full Prescribing Information, including both Patient Information and Instructions for Use, for complete safety and administration information. About Jazz Pharmaceuticals Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases – often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information. Contacts:Media: Kristin Bhavnani Head of Global Corporate Communications Jazz Pharmaceuticals plc CorporateAffairsMediaInfo@jazzpharma.comIreland +353 1 637 2141 U.S. +1 215 867 4948 Investors: Jack Spinks Executive Director, Investor Relations Jazz Pharmaceuticals plc investorinfo@jazzpharma.com Ireland +353 1 634 3211 U.S. +1 650 496 2717 1 MODEYSO (dordaviprone) Prescribing Information. Palo Alto, CA : Jazz Pharmaceuticals, Inc. 2 Yang, Z., Sun, L., Chen, et al. New progress in the treatment of diffuse midline glioma with H3K27M alteration. Heliyon. 2024;10(2).3 National Cancer Institute . Diffuse Midline Glioma: Diagnosis and Treatment. Updated August 20, 2024 . Accessed September 8, 2025 . https://www.cancer.gov/rare-brain-spine-tumor/tumors/diffuse-midline-gliomas4 ClinicalTrials.gov. ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) (ACTION). Updated August 26, 2025 . Accessed September 8, 2025 . Study Details | ONC201 in H3 K27M-mutant Diffuse Glioma Following Radiotherapy (the ACTION Study) | ClinicalTrials.gov5 Bagley, S. J., Umemura, et al. Prognostic Features of Recurrent Midline and H3 K27M-Mutant Glioma. Cancers. 2025;17(13):2107. https://doi.org/10.3390/cancers17132107 View original content to download multimedia:https://www.prnewswire.com/news-releases/modeyso-dordaviprone-included-in-national-comprehensive-cancer-network-nccn-clinical-practice-guidelines-in-oncology-for-h3-k27m-mutant-diffuse-glioma-302549794.html SOURCE Jazz Pharmaceuticals plc

iStock, leolintang After receiving a complete response letter for its pyruvate dehydrogenase complex deficiency candidate, Saol Therapeutics anticipates it will need “several years” and “significant financial resources” to address the FDA’s concerns. The FDA has rejected Saol Therapeutics’ application for SL1009, which it was proposing for the treatment of pyruvate dehydrogenase complex deficiency, an ultra-rare mitochondrial disease in children. Saol did not reveal the regulator’s reasons for the rejection, only announcing that the Complete Response Letter detailed “specific observations” that the privately held biotech “will need to address to clarify the path forward.” The FDA’s findings and recommendations for resolution could prove too burdensome for Saol. “To address the deficiencies as the FDA requested, it would take several years and require significant financial resources,” the company wrote on Monday. Currently, Saol is working with the FDA to find a way forward for SL1009 “that does not require an additional trial,” as per its announcement . Affecting less than 1,000 patients in the U.S. and occurring in about 90 births per year, pyruvate dehydrogenase complex deficiency (PDCD) is characterized by the toxic buildup of lactic acid in the body, resulting in what Saol calls “overwhelming health challenges.” These include nausea, vomiting, severe breathing problems, neurological impairments and an abnormal heartbeat. Most patients with PDCD do not live beyond early childhood. There are no approved treatments for the disease. Saol’s SL1009 is an oral formulation of sodium dichloroacetate that had previously won the FDA’s orphan drug, rare pediatric disease and priority review designations for PDCD. The drug is designed to be used with a proprietary genetic test. In a statement on Friday, days before Saol’s formal announcement of the CRL, the United Mitochondrial Disease, a nonprofit pushing for diagnosis, treatment and cure of mitochondrial diseases, released an open letter to express its “ deep disappointment ” with the FDA’s rejection. The decision, according to the group, could delay access to life-saving therapies, in turn leading to “irreversible damage – or even death.” “While we fully support rigorous scientific standards, regulatory flexibility is essential for rare disease populations like PDCD,” the open letter read. Other patient advocacy groups, including MitoAction, Cure Mito Foundation, Hope for PDCD and the Elizabeth Watt PDCD Research Fund, also signed the letter. Monday’s PDCD rejection comes after a standout month for the rare disease space, which in August secured four regulatory firsts . Jazz Pharmaceuticals’ Modeyso , for instance, became the industry’s first drug for diffuse midline glioma with an H3 K27M mutation. Then, Insmed’s Brinsupri secured the FDA’s first approval for non-cystic fibrosis bronchiectasis—and also became the first therapy that blocks the DPP1 enzyme. Last month, Precigen’s Papzimeos likewise became the “ first-of-its-kind ” non-replicating immunotherapy for recurrent respiratory papillomatosis. Finally, Ionis’ Dawnzera secured the industry’s first RNA-targeting prophylactic nod for hereditary angioedema.

iStock, Deagreez According to analysts, the new data could present a path to accelerated approval for ifinatamab deruxtecan, a product of Merck and Daiichi Sankyo’s troubled ADC partnership. Nearly half of patients dosed with Merck and Daiichi Sankyo’s ifinatamab deruxtecan responded to the treatment, helping the partners mount a comeback for their antibody-drug conjugate alliance. Results from the Phase II IDeate-Lung01 study, presented Sunday at the 2025 World Conference on Lung Cancer, showed that the drug, also known as I-DXd, resulted in a 48.2% confirmed objective response rate (ORR) in patients with extensive-stage small cell lung cancer. These data include three complete responses and 63 partial responses; 54 of the treated patients achieved stable disease. Writing to investors on Sunday evening, Jefferies analysts called I-DXd’s performance “strong,” noting, however, that these latest data are “lower” than what Merck and Daiichi Sankyo had toplined at last year’s WCLC. At the time, the partners announced a 54.8% ORR . According to Jeffries, the difference in the two figures came from Sunday’s data, including patients receiving I-DXd in a third-line setting, which could potentially have “diluted” the therapy’s efficacy figures. Focusing on a subset of participants who received I-DXd in the second-line setting, ORR was 56.3%, which Jefferies said was “impressive.” Given these findings, as well as the breakthrough therapy designation the drug received from the FDA last month, Jefferies believes that an accelerated approval for I-DXd in this indication could be a “distinct possibility.” The FDA has previously demonstrated regulatory flexibility for small-cell lung cancer, with accelerated approvals for Jazz Pharmaceuticals’ Zepzelca and Amgen’s Imdelltra , both drugs working their way through the accelerated pathway, based on pivotal Phase II data. Sunday’s pivotal readout represents a much-needed win for Merck and Daiichi Sankyo’s antibody-drug conjugate (ADC) collaboration. The companies linked up in October 2023, when Merck paid $4 billion upfront for access to three investigational therapies for solid tumors. All told, Merck could be on the hook for $22 billion. In June 2024, however, one of the assets under this partnership, patritumab deruxtecan, failed to win the FDA’s approval for locally advanced or metastatic non-small cell lung cancer. Manufacturing problems stymied the application, the companies announced at the time, insisting that there had been no problems with the molecule’s safety or efficacy. Then, in May this year, Merck and Daiichi Sankyo decided to pull that application completely, noting that the ADC did not show significant overall survival improvements in a Phase III study. It is unclear if they plan to resubmit an approval application for this asset.