FDA Provides Seven Years of Orphan-Drug Exclusive Approval for Ryoncil®
NEW YORK, May 14, 2025 (GLOBE NEWSWIRE) -- Mesoblast (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that it has received seven years of orphan-drug exclusive approval from U.S. Food and Drug Administration (FDA) for Ryoncil® (remestemcel-L) for treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months of age and older.
This period of statutory exclusivity means that the FDA will not approve another mesenchymal stromal or stem cell (MSC) products for this indication during the 7-year period from the approval of Ryoncil®. Separately, Mesoblast has biologic exclusivity preventing another sponsor from referencing the Ryoncil® biologic license application (BLA) until December 2036, twelve years from its first approval which would prevent market entry by a biosimilar.
These statutory exclusivities are in addition to Mesoblast's strong U.S. intellectual property position on MSC composition of matter, manufacturing and indications, including SR-aGvHD, that provide a commercial barrier to entry against competitors through 2044.
About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The therapies from the Company's proprietary mesenchymal lineage cell therapy technology platform respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process.
Mesoblast's RYONCIL® (remestemcel-L) for the treatment of steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients 2 months and older is the first FDA approved mesenchymal stromal cell (MSC) therapy. Please see the full Prescribing Information at www.ryoncil.com.
Mesoblast is committed to developing additional cell therapies for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. RYONCIL is being developed for additional inflammatory diseases including SR-aGvHD in adults and biologic-resistant inflammatory bowel disease. Rexlemestrocel-L is being developed for heart failure and chronic low back pain. The Company has established commercial partnerships in Japan, Europe and China.
About Mesoblast intellectual property: Mesoblast has a strong and extensive global intellectual property portfolio, with over 1,000 granted patents or patent applications covering mesenchymal stromal cell compositions of matter, methods of manufacturing and indications. These granted patents and patent applications are expected to provide commercial protection extending through to at least 2044 in major markets.
About Mesoblast manufacturing: The Company's proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.
Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast.
Forward-Looking StatementsThis press release includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance or achievements to differ materially from any future results, levels of activity, performance or achievements expressed or implied by these forward-looking statements. We make such forward-looking statements pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Forward-looking statements should not be read as a guarantee of future performance or results, and actual results may differ from the results anticipated in these forward-looking statements, and the differences may be material and adverse. Forward-looking statements include, but are not limited to, statements about: the initiation, timing, progress and results of Mesoblast's preclinical and clinical studies, and Mesoblast's research and development programs; Mesoblast's ability to advance product candidates into, enroll and successfully complete, clinical studies, including multi-national clinical trials; Mesoblast's ability to advance its manufacturing capabilities; the timing or likelihood of regulatory filings and approvals, manufacturing activities and product marketing activities, if any; the commercialization of Mesoblast's RYONCIL for pediatric SR-aGVHD and any other product candidates, if approved; regulatory or public perceptions and market acceptance surrounding the use of stem-cell based therapies; the potential for Mesoblast's product candidates, if any are approved, to be withdrawn from the market due to patient adverse events or deaths; the potential benefits of strategic collaboration agreements and Mesoblast's ability to enter into and maintain established strategic collaborations; Mesoblast's ability to establish and maintain intellectual property on its product candidates and Mesoblast's ability to successfully defend these in cases of alleged infringement; the scope of protection Mesoblast is able to establish and maintain for intellectual property rights covering its product candidates and technology; estimates of Mesoblast's expenses, future revenues, capital requirements and its needs for additional financing; Mesoblast's financial performance; developments relating to Mesoblast's competitors and industry; and the pricing and reimbursement of Mesoblast's product candidates, if approved. You should read this press release together with our risk factors, in our most recently filed reports with the SEC or on our website. Uncertainties and risks that may cause Mesoblast's actual results, performance or achievements to be materially different from those which may be expressed or implied by such statements, and accordingly, you should not place undue reliance on these forward-looking statements. We do not undertake any obligations to publicly update or revise any forward-looking statements, whether as a result of new information, future developments or otherwise.
Release authorized by the Chief Executive.
For more information, please contact:
Paul Hughes
T: +61 3 9639 6036
Allison Worldwide
Emma Neal
T: +1 603 545 4843
E: emma.neal@allisonworldwide.com
BlueDot Media
Steve Dabkowski
T: +61 419 880 486
E: steve@bluedot.net.au
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Additionally, participants showed minimal changes in the number of central apnea events, mean oxygen saturation (SpO2) levels, or the mean percent of total sleep time with SpO2 <90% from BL to EOT. The DUET trial is a Phase 4, prospective, single-arm, open-label study to assess the effect of Xywav treatment on EDS, polysomnography parameters, and functional outcomes in adults with narcolepsy or IH. Overall, TEAEs were all mild or moderate and consistent with the known safety profile of Xywav at lower dosages. The full abstracts will be available online at About NarcolepsyNarcolepsy is a chronic, debilitating neurologic sleep disorder characterized by the inability to maintain continuous sleep at night and sustained wakefulness throughout the day. This leads to symptoms that can include fragmented or disrupted nighttime sleep, excessive daytime sleepiness, and cataplexy.1 Patients with EDS due to narcolepsy experience sleep attacks, called cataplexy, and, despite fighting the urge to sleep, may unintentionally fall asleep for short periods.2,3 These sleep attacks may happen at inappropriate or potentially dangerous times such as during driving, cycling, eating, or mid-conversation.4 There is no cure for narcolepsy, therefore this EDS is lifelong and has a substantial negative impact on a person's ability to function psychologically, socially and professionally.5 Patients with narcolepsy are at increased risk for hypertension, cardiometabolic morbidity, stroke, myocardial infarction, heart failure, cardiac arrest, and death.6,7,8,9 As narcolepsy is a chronic condition that requires lifelong, nightly treatment, early access to an effective, low-sodium treatment can transform lives and reduce the impact of narcolepsy on a person's physical and mental health.5 About Xywav® (calcium, magnesium, potassium, and sodium oxybates) oral solutionXywav is the only low-sodium oxybate approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy. 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Xywav is the only oxybate therapy that does not carry a warning in the label related to use in patients sensitive to high sodium intake. Xywav is also the first and only U.S. FDA-approved treatment option for idiopathic hypersomnia in adults. The FDA recognized seven years of Orphan Drug Exclusivity for Xywav for the treatment of idiopathic hypersomnia in adults. Xywav is the only FDA-approved treatment studied across the multiple symptoms of idiopathic hypersomnia, such as EDS, sleep inertia (severe grogginess or confusion when waking up), long sleep duration and cognitive impairment. Xywav can be administered as a twice- or once-nightly regimen for the treatment of idiopathic hypersomnia in adults. The exact mechanism of action of Xywav in the treatment of adults with idiopathic hypersomnia and of cataplexy and EDS in narcolepsy is unknown. It is hypothesized that the therapeutic effects of Xywav are mediated through GABAB actions during sleep at noradrenergic and dopaminergic neurons, as well as thalamocortical neurons.10 The U.S. Drug Enforcement Agency (DEA) has designated Xywav as a Schedule III medicine. The DEA defines Schedule III drugs, substances, or chemicals as drugs with a moderate to low potential for physical and psychological dependence.10,11 Because of the risks of central nervous system (CNS) depression and abuse and misuse, Xywav is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS. Important Safety Information for Xywav WARNING: CENTRAL NERVOUS SYSTEM DEPRESSION and ABUSE AND MISUSE. Central Nervous System DepressionXYWAV is a CNS depressant. Clinically significant respiratory depression and obtundation may occur in patients treated with XYWAV at recommended doses. Many patients who received XYWAV during clinical trials in narcolepsy and idiopathic hypersomnia were receiving CNS stimulants. Abuse and MisuseThe active moiety of XYWAV is oxybate or gamma-hydroxybutyrate (GHB). Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death. Because of the risks of CNS depression and abuse and misuse, XYWAV is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XYWAV and XYREM REMS. ContraindicationsXYWAV is contraindicated in combination with sedative hypnotics or alcohol and in patients with succinic semialdehyde dehydrogenase deficiency. Warnings and PrecautionsCentral Nervous System DepressionThe concurrent use of XYWAV with other CNS depressants, including but not limited to opioid analgesics, benzodiazepines, sedating antidepressants or antipsychotics, sedating anti-epileptic drugs, general anesthetics, muscle relaxants, and/or illicit CNS depressants, may increase the risk of respiratory depression, hypotension, profound sedation, syncope, and death. If use of these CNS depressants in combination with XYWAV is required, dose reduction or discontinuation of one or more CNS depressants (including XYWAV) should be considered. In addition, if short-term use of an opioid (eg, post- or perioperative) is required, interruption of treatment with XYWAV should be considered. After first initiating treatment and until certain that XYWAV does not affect them adversely (eg, impair judgment, thinking, or motor skills), caution patients against hazardous activities requiring complete mental alertness or motor coordination such as operating hazardous machinery, including automobiles or airplanes. Also caution patients against these hazardous activities for at least 6 hours after taking XYWAV. Patients should be queried about CNS depression-related events upon initiation of XYWAV therapy and periodically thereafter. Abuse and MisuseXYWAV is a Schedule Ill controlled substance. The active moiety of XYWAV is oxybate, also known as gamma-hydroxybutyrate (GHB), a Schedule I controlled substance. Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death. The rapid onset of sedation, coupled with the amnestic features of GHB particularly when combined with alcohol, has proven to be dangerous for the voluntary and involuntary user (eg, assault victim). Physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely. XYWAV and XYREM REMSBecause of the risks of central nervous system depression and abuse and misuse, XYWAV is available only through a restricted distribution program called the XYWAV and XYREM REMS. Notable requirements of the XYWAV and XYREM REMS include the following: Healthcare Providers who prescribe XYWAV are specially certified XYWAV will be dispensed only by the central pharmacy that is specially certified XYWAV will be dispensed and shipped only to patients who are enrolled in the XYWAV and XYREM REMS with documentation of safe use Further information is available at or 1-866-997-3688. Respiratory Depression and Sleep-Disordered BreathingXYWAV may impair respiratory drive, especially in patients with compromised respiratory function. In overdoses of oxybate and with illicit use of GHB, life-threatening respiratory depression has been reported. Increased apnea and reduced oxygenation may occur with XYWAV administration in adult and pediatric patients. A significant increase in the number of central apneas and clinically significant oxygen desaturation may occur in patients with obstructive sleep apnea treated with XYWAV. Prescribers should be aware that sleep-related breathing disorders tend to be more prevalent in obese patients, in men, in postmenopausal women not on hormone replacement therapy, and among patients with narcolepsy. Depression and SuicidalityIn Study 1, the randomized-withdrawal clinical trial in adult patients with narcolepsy (n=201), depression and depressed mood were reported in 3% and 4%, respectively, of patients treated with XYWAV. Two patients (1%) discontinued XYWAV because of depression. In most cases, no change in XYWAV treatment was required. In Study 2, the randomized-withdrawal clinical trial in adult patients with idiopathic hypersomnia (n=154), depression and depressed mood were reported in 1% and 3%, respectively, of patients treated with XYWAV. All patients continued XYWAV treatment. Two suicides and two attempted suicides occurred in adult clinical trials with oxybate (same active moiety as XYWAV). One patient experienced suicidal ideation and two patients reported depression in a pediatric clinical trial with oxybate. These events occurred in patients with and without previous histories of depressive disorders. The emergence of depression in patients treated with XYWAV requires careful and immediate evaluation. Monitor patients for the emergence of increased depressive symptoms and/or suicidality while taking XYWAV. Other Behavioral or Psychiatric Adverse ReactionsIn Study 1, confusion and anxiety occurred in 1% and 5% of patients with narcolepsy treated with XYWAV, respectively. One patient experienced visual hallucinations and confusion after ingesting approximately 9 grams of XYWAV. In Study 2, confusion and anxiety occurred in 3% and 16% of patients with idiopathic hypersomnia, respectively. One patient experienced visual hallucinations, which led to discontinuation of XYWAV. Other neuropsychiatric reactions reported with oxybate (same active moiety as XYWAV) in adult or pediatric clinical trials and in the postmarketing setting include hallucinations, paranoia, psychosis, aggression, agitation, confusion and anxiety. The emergence or increase in the occurrence of behavioral or psychiatric events in patients taking XYWAV should be carefully monitored. ParasomniasParasomnias can occur in patients taking XYWAV. In Study 1 and Study 2, parasomnias, including sleepwalking, were reported in 6% and 5% of adult patients treated with XYWAV, respectively. In a clinical trial of XYREM (same active moiety as XYWAV) in adult patients with narcolepsy, five instances of sleepwalking with potential injury or significant injury were reported. Parasomnias, including sleepwalking, have been reported in a pediatric clinical trial with sodium oxybate (same active moiety as XYWAV) and in postmarketing experience with sodium oxybate. Episodes of sleepwalking should be fully evaluated and appropriate interventions considered. Most Common Adverse ReactionsThe most common adverse reactions (occurring in ≥5% of XYWAV-treated patients in adult clinical trials in either narcolepsy or IH) were nausea, headache, dizziness, anxiety, insomnia, decreased appetite, hyperhidrosis, vomiting, diarrhea, dry mouth, parasomnia, somnolence, fatigue, and tremor. In the pediatric clinical trial with XYREM (same active moiety as XYWAV) that included pediatric patients 7 to 17 years of age with narcolepsy, the most common adverse reactions (≥5%) were nausea (20%), enuresis (19%), vomiting (18%), headache (17%), weight decreased (13%), decreased appetite (9%), dizziness (8%), and sleepwalking (6%). The overall adverse reaction profile of XYREM in the pediatric clinical trial was similar to that seen in the adult clinical trial program. The safety profile in pediatric patients with XYWAV is expected to be similar to that of adult patients treated with XYWAV and to that of pediatric patients treated with XYREM. Additional Adverse ReactionsAdverse reactions that occurred in 2-<5% of adult patients treated with XYWAV in the Open Label Titration and Stable Dose Periods of the randomized-withdrawal study in adult patients with narcolepsy with cataplexy (Study 1) were fatigue, dry mouth, depressed mood, enuresis, irritability, paresthesia, depression, tremor, somnolence, and muscle spasms. Adverse reactions occurring in 2-<5% of patients treated with XYWAV in the IH study include balance disorder, muscle spasms, fall, paresthesia, snoring, weight decreased, bruxism, confusional state, depressed mood, feeling drunk, and irritability. Adverse reactions that occurred in ≥2% of patients in clinical studies with oxybate (but not in Study 1) and which may be relevant for XYWAV, were pain, feeling drunk, pain in extremity, cataplexy, disturbance in attention, sleep paralysis, and disorientation. Discontinuation: In Study 1, 9 of 201 patients (4%) reported adverse reactions that led to withdrawal from the study (anxiety, decreased appetite, depressed mood, depression, fatigue, headache, irritability, nausea, pain in extremity, parasomnia, somnolence, and vomiting). The most common adverse reaction leading to discontinuation was nausea (1.5%). In Study 2, 17 of 154 (11%) patients across all study periods (excluding placebo during the DB RWP) (up to 42 weeks) reported adverse reactions that led to withdrawal from the study (anxiety, nausea, insomnia, vomiting, fatigue, feeling abnormal, fall, decreased appetite, dizziness, paresthesia, tremor, parasomnia, confusional state, hallucination visual, and irritability). The most common adverse reaction leading to discontinuation was anxiety (3.2%). In Study 1 and Study 2, the majority of adverse reactions leading to discontinuation began during the first few weeks of treatment. In the pediatric clinical trial with XYREM (same active moiety as XYWAV), 7 of 104 patients reported adverse reactions that led to withdrawal from the study (hallucination, tactile; suicidal ideation; weight decreased; sleep apnea syndrome; affect lability; anger, anxiety, depression; and headache). Drug InteractionsXYWAV is contraindicated in combination with alcohol or sedative hypnotics. Use of other CNS depressants may potentiate the CNS-depressant effects of XYWAV. Concomitant use of sodium oxybate with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study. A similar increase in exposure is expected with concomitant use of XYWAV and divalproex sodium; therefore, an initial dose reduction of XYWAV is recommended when used concomitantly with divalproex sodium. Prescribers are advised to monitor patient response closely and adjust dose accordingly if concomitant use of XYWAV and divalproex sodium is warranted. Pregnancy and LactationThere are no adequate data on the developmental risk associated with the use of XYWAV or sodium oxybate in pregnant women. XYWAV should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. GHB is excreted in human milk after oral administration of sodium oxybate. There is insufficient information on the risk to a breastfed infant, and there is insufficient information on milk production in nursing mothers. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for XYWAV and any potential adverse effects on the breastfed infant from XYWAV or from the underlying maternal condition. Pediatric UseThe safety and effectiveness of XYWAV for the treatment of cataplexy or excessive daytime sleepiness in pediatric patients 7 years of age and older with narcolepsy have been established. XYWAV has not been studied in a pediatric clinical trial for narcolepsy or IH. Use of XYWAV in pediatric patients 7 years of age and older with narcolepsy is supported by evidence from an adequate and well-controlled study of sodium oxybate in pediatric patients 7 to 17 years of age, a study in adults showing a treatment effect of XYWAV similar to that observed with sodium oxybate, pharmacokinetic data of sodium oxybate from adult and pediatric patients, and pharmacokinetic data of XYWAV from healthy adult volunteers. Safety and effectiveness of XYWAV in pediatric patients below the age of 7 years with narcolepsy have not been established. Safety and effectiveness of XYWAV for the treatment of idiopathic hypersomnia in pediatric patients have not been established. Geriatric UseIn general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Hepatic ImpairmentThe starting dose of XYWAV should be reduced in patients with liver impairment. Dosage Modification in Patients with Hepatic Impairment: The recommended starting dosage in patients with hepatic impairment is one-half of the original dosage per night, administered orally, divided into two doses. Dependence and ToleranceThere have been case reports of withdrawal, ranging from mild to severe, following discontinuation of illicit use of GHB at frequent repeated doses (18 g to 250 g per day) in excess of the recommended dosage range. Signs and symptoms of GHB withdrawal following abrupt discontinuation included insomnia, restlessness, anxiety, psychosis, lethargy, nausea, tremor, sweating, muscle cramps, tachycardia, headache, dizziness, rebound fatigue and sleepiness, confusion, and, particularly in the case of severe withdrawal, visual hallucinations, agitation, and delirium. These symptoms generally abated in 3 to 14 days. In cases of severe withdrawal, hospitalization may be required. In the clinical trial experience with XYREM in narcolepsy/cataplexy patients at recommended doses, two patients reported anxiety and one reported insomnia following abrupt discontinuation at the termination of the clinical trial; in the two patients with anxiety, the frequency of cataplexy had increased markedly at the same time. In the XYWAV clinical trial in adult narcolepsy/cataplexy patients at recommended doses, one patient reported insomnia following abrupt discontinuation of XYWAV. In the XYWAV clinical trial in adult idiopathic hypersomnia patients at recommended doses, six patients reported insomnia, two patients reported early insomnia, and one patient reported visual and auditory hallucinations following abrupt discontinuation of XYWAV. Tolerance to XYWAV has not been systematically studied in controlled clinical trials. There have been some case reports of symptoms of tolerance developing after illicit use at dosages far in excess of the recommended XYWAV dosage regimen. Please see full Prescribing Information, including BOXED Warning here: About Jazz PharmaceuticalsJazz 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 for more information. Contacts: Media:Kristin BhavnaniHead of Global Corporate CommunicationsJazz Pharmaceuticals plcCorporateAffairsMediaInfo@ Ireland +353 1 637 2141U.S. +1 215 867 4948 Investors:Jeff MacdonaldExecutive Director, Investor RelationsJazz Pharmaceuticals plcInvestorInfo@ +353 1 634 3211U.S. +1 650 496 2717 References: Sateia, M. J. (2023). International Classification of Sleep Disorders-Third Edition, Text Revision (ICSD-3-TR). Chest, 146(5), 1387–1394. PubMed. Dauvilliers Y, Arnulf I, Mignot E. Narcolepsy with cataplexy. Lancet. 2007;369(9560):499-511. Colten HR, Altevogt BM, Institute of Medicine (US) Committee on Sleep Medicine and Research, eds. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington (DC): National Academies Press (US); 2006. Peacock J, Benca RM. Narcolepsy: clinical features, co-morbidities & treatment. Indian Journal of Medical Research. 2010;131(2):338-349. National Health Service. Narcolepsy – Overview. 2019. Accessed June 2025. Ben-Joseph RH, Saad R, Black J, et al. Cardiovascular burden of narcolepsy disease (CV-BOND): a real-world evidence study. Presented at: 2022 AAN Annual Meeting; April 2-7; Seattle, Washington. Poster 1203. Black J, Reaven NL, Funk SE, et al. Medical comorbidity in narcolepsy: findings from the Burden of Narcolepsy Disease (BOND) study. Sleep Med. 2017;33:13-18. Ohayon MM, Black J, Lai C, et al. Increased mortality in narcolepsy. Sleep. 2014;37(3):439-444. Ohayon MM. Narcolepsy is complicated by high medical and psychiatric comorbidities: a comparison with the general population. Sleep Med. 2013;14(6):488-492. Xywav (calcium, magnesium, potassium and sodium oxybates) oral solution. Prescribing Information. Palo Alto, CA: Jazz Pharmaceuticals, Inc. 2021. United States Drug Enforcement Agency. Drug Scheduling. Accessed June 2025. View original content to download multimedia: SOURCE Jazz Pharmaceuticals plc Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
