Avadel Announces Publications in CNS Drugs Supplement Highlighting Key Clinical Issues for People with Narcolepsy and Their Clinicians

DUBLIN, March 25, 2025 (GLOBE NEWSWIRE) -- Avadel Pharmaceuticals plc (NASDAQ:AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, today announced the publication of six manuscripts covering clinical management, shared decision-making and goal setting for people with narcolepsy and their clinicians in a CNS Drugs supplement titled "A New Dawn in the Management of Narcolepsy".

"I am delighted to serve as guest editor for the recently published CNS Drugs supplement, focused on key clinical issues for people with narcolepsy and their clinicians with a particular emphasis on sodium oxybate therapy, an underutilized treatment option," said Michael J. Thorpy, M.D., an investigator for the Phase 3 REST-ON trial of LUMRYZ™, Director at the Sleep-Wake Disorders Center at Montefiore Medical Center and Professor of Neurology at the Albert Einstein College of Medicine. "This supplement provides clinicians with important information about how to optimize therapy to help address narcolepsy symptoms, including new analyses of onset of efficacy and practical considerations for use of a once-nightly sodium oxybate therapy, to enable clinicians to set proper expectations when initiating LUMRYZ therapy."

Summary of Papers in CNS Drugs Supplement

Paper Title	Authors/Synopsis
Narcolepsy: Beyond the Classic Pentad	Authored by Anne Marie Morse, D.O., Director of Pediatric Neurology at Geisinger Medical Center and others, this paper addresses the full 24-hour impact and symptom burden that patients experience, as well as the need for an individualized treatment approach and care considerations that extend beyond the hallmark features of the disease.
A Survey of People Living With Narcolepsy in the USA: Path to Diagnosis, Quality of Life, and Treatment Landscape From the Patient's Perspective	Authored by Luis E. Ortiz, M.D., Assistant Professor of Pediatrics at Johns Hopkins Medicine and others, the survey reports data from 110 people living with narcolepsy. Among the key findings: nearly three-fourths (72%) of respondents experienced some form of nighttime sleep disturbance (such as disrupted nighttime sleep and fragmented sleep) and approximately one-third (33%) of sodium oxybate users reported their top treatment goal was medicine to help them sleep through the night.
Therapeutic Use of γ-Hydroxybutyrate: History and Clinical Utility of Oxybates and Considerations of Once and Twice-Nightly Dosing in Narcolepsy	Authored by Thomas Roth, Ph.D., founder of the Sleep Disorders and Research Center at Henry Ford Health, this paper provides a 50-year historical overview of γ-Hydroxybutyrate (GHB) use in narcolepsy, including more than two decades of safe and appropriate use as a treatment. The paper also includes data on changes to sleep architecture that occur during treatment with LUMRYZ, aligning with a more "normal" sleep pattern in people with narcolepsy vs. chronic middle-of-the-night awakening.
Assessing Early Efficacy After Initiation of Once-Nightly Sodium Oxybate (ON-SXB; FT218) in Participants With Narcolepsy Type 1 or 2: A Post Hoc Analysis From the Phase 3 REST-ON Trial	Authored by Lois E. Krahn, M.D., Professor of Psychiatry at the Mayo Clinic College of Medicine and others, this analysis demonstrates significant improvements in certain narcolepsy symptoms (including sleep quality and refreshing nature of sleep) with LUMRYZ versus placebo one to two weeks after treatment initiation, with increasing improvement from week 3 onward.
Efficacy of Once-Nightly Sodium Oxybate in Patients With Narcolepsy: Post Hoc Analyses of Sensitivity, Effect Size, and Numbers Needed to Treat From the Phase 3 REST-ON Trial	Also authored by Dr. Roth and others, this paper provides further validation of the robust efficacy once-nightly LUMRYZ demonstrated in the REST-ON trial across primary and secondary endpoints.
Sodium Oxybate: Practical Considerations and Patient Perspectives	Authored by Maggie Lavender, M.S.N., of Comprehensive Sleep Medicine Associates in Houston, Texas and others, this paper includes illustrative clinical case scenarios of two people with narcolepsy, providing clinicians with a proposed framework to optimize discussions with patients and demystify sodium oxybate treatment, providing practical tips and support for initiating and maintaining therapy.

"Despite sodium oxybate being FDA-approved for more than two decades and strongly recommended by the American Academy of Sleep Medicine for nearly 20 years, this therapy remains underutilized – in part due to the historical burdensome dosing for first-generation oxybates. The title of this supplement, A New Dawn in the Management of Narcolepsy, reflects that the patient community no longer needs to accept the status quo," said Jennifer Gudeman, Pharm.D., Senior Vice President, Medical and Clinical Affairs of Avadel.

"These publications illustrate the impact of nighttime sleep disturbances on narcolepsy patients, highlight the robust data supporting LUMRYZ, and perhaps most importantly, demystify oxybate therapy, with a particular focus on LUMRYZ initiation and maintenance of therapy," continued Dr. Gudeman. "Patients taking once-nightly LUMRYZ may experience transient tolerability effects, coupled with some degree of symptom relief after one to two weeks and increasing improvement from week three onward, which may help clinicians set expectations with patients to improve medication adherence."

About LUMRYZ™ (sodium oxybate) for extended-release oral suspension 

LUMRYZ is an extended-release sodium oxybate medication approved by the FDA on May 1, 2023, as the first and only once-at-bedtime treatment for cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.  On October 16, 2024, LUMRYZ was additionally approved as a once-at-bedtime treatment for cataplexy or EDS in patients 7 years of age and older with narcolepsy.

The FDA approval of LUMRYZ was supported by results from REST-ON, a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial in adults with narcolepsy. LUMRYZ demonstrated statistically significant and clinically meaningful improvements in the three co-primary endpoints: EDS, clinicians' overall assessment of patients' functioning (CGI-I) and cataplexy attacks, for all three evaluated doses when compared to placebo.

With its approval, the FDA also granted seven years of Orphan Drug Exclusivity to LUMRYZ for the treatment of cataplexy or EDS in adults with narcolepsy due to a finding of clinical superiority of LUMRYZ relative to currently available oxybate treatments. In particular, the FDA found that LUMRYZ makes a major contribution to patient care over currently available, twice-nightly oxybate products by providing a once-nightly dosing regimen that avoids nocturnal arousal to take a second dose. A second 7-year period of Orphan Drug Exclusivity was granted with the approval of the expanded indication in October 2024.

INDICATIONS

LUMRYZ (sodium oxybate) for extended-release oral suspension is a prescription medicine used to treat the following symptoms in patients 7 years of age and older with narcolepsy:

• sudden onset of weak or paralyzed muscles (cataplexy)
• excessive daytime sleepiness (EDS)

IMPORTANT SAFETY INFORMATION

WARNING: Taking LUMRYZ™ (sodium oxybate) with other central nervous system (CNS) depressants, such as medicines used to make you fall asleep, including opioid analgesics, benzodiazepines, sedating antidepressants, antipsychotics, sedating anti-epileptic medicines, general anesthetics, muscle relaxants, alcohol or street drugs, may cause serious medical problems, including trouble breathing (respiratory depression), low blood pressure (hypotension), changes in alertness (drowsiness), fainting (syncope) and death. The active ingredient of LUMRYZ (sodium oxybate) is a form of gamma hydroxybutyrate (GHB), a controlled substance. Abuse or misuse of illegal GHB alone or with other CNS depressants (drugs that cause changes in alertness or consciousness) have caused serious side effects. These effects include seizures, trouble breathing (respiratory depression), changes in alertness (drowsiness), coma and death. Call your doctor right away if you have any of these serious side effects. Because of these risks, LUMRYZ is available only by prescription and filled through certified pharmacies in the LUMRYZ REMS. You must be enrolled in the LUMRYZ REMS to receive LUMRYZ. Further information is available at www.LUMRYZREMS.com or by calling 1-877-453-1029.

Do not take LUMRYZ if you take or your child takes other sleep medicines or sedatives (medicines that cause sleepiness), drink alcohol or have a rare problem called succinic semialdehyde dehydrogenase deficiency.

Keep LUMRYZ in a safe place to prevent abuse and misuse. Selling or giving away LUMRYZ may harm others and is against the law. Tell your doctor if you or your child have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Anyone who takes LUMRYZ should not do anything that requires them to be fully awake or is dangerous, including driving a car, using heavy machinery or flying an airplane, for at least six (6) hours after taking LUMRYZ. Those activities should not be done until you know how LUMRYZ affects you.

Falling asleep quickly, including while standing or while getting up from the bed, has led to falls with injuries that have required some people to be hospitalized.

LUMRYZ can cause serious side effects, including the following:

• Breathing problems, including slower breathing, trouble breathing and/or short periods of not breathing while sleeping (e.g., sleep apnea). People who already have breathing or lung problems have a higher chance of having breathing problems when they take LUMRYZ.
• Mental health problems, including confusion, seeing or hearing things that are not real (hallucinations), unusual or disturbing thoughts (abnormal thinking), feeling anxious or upset, depression, thoughts of killing yourself or trying to kill yourself, increased tiredness, feelings of guilt or worthlessness and difficulty concentrating. Tell your doctor if you or your child have or had depression or have tried to harm yourself. Call your doctor right away if you or your child have symptoms of mental health problems or a change in weight or appetite.
• Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you or your child start sleepwalking.
  
  

Tell your doctor if you or your child are on a salt-restricted diet or have high blood pressure, heart failure or kidney problems. LUMRYZ contains a lot of sodium (salt) and may not be right for you.

The most common side effects of LUMRYZ in adults include nausea, dizziness, bedwetting, headache and vomiting. Your side effects may increase when you take higher doses of LUMRYZ. The most common side effects in children include nausea, bedwetting, vomiting, headache, decreased weight, decreased appetite, dizziness, and sleepwalking. LUMRYZ can cause physical dependence and craving for the medicine when it is not taken as directed. These are not all the possible side effects of LUMRYZ.

For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see full Prescribing Information, including BOXED Warning.

About Avadel Pharmaceuticals plc

Avadel Pharmaceuticals plc (NASDAQ:AVDL) is a biopharmaceutical company focused on transforming medicines to transform lives. Our approach includes applying innovative solutions to the development of medications that address the challenges patients face with current treatment options. Avadel's commercial product, LUMRYZ, was approved by the U.S. Food & Drug Administration (FDA) as the first and only once-at-bedtime oxybate for the treatment of cataplexy or EDS in both adults and pediatrics with narcolepsy. For more information, please visit www.avadel.com.

Avadel intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company's Investor Relations website, in addition to following the Company's press releases, SEC filings, public conference calls, presentations, and webcast.

Cautionary Disclosure Regarding Forward-Looking Statements

This press release includes "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements relate to our future expectations, beliefs, plans, strategies, objectives, results, conditions, financial performance, prospects or other events. Such forward-looking statements include, but are not limited to, expectations regarding the safety, tolerability and potential therapeutic benefit of LUMRYZ; and expectations regarding potential benefits of the publications. In some cases, forward-looking statements can be identified by the use of words such as "will," "may," "could," "believe," "expect," "look forward," "on track," "guidance," "anticipate," "estimate," "project," "next steps" and similar expressions and the negatives thereof (if applicable).

The Company's forward-looking statements are based on estimates and assumptions that are made within the bounds of our knowledge of our business and operations and that we consider reasonable. However, the Company's business and operations are subject to significant risks, and, as a result, there can be no assurance that actual results and the results of the company's business and operations will not differ materially from the results contemplated in such forward-looking statements. Factors that could cause actual results to differ from expectations in the Company's forward-looking statements include the risks and uncertainties described in the "Risk Factors" section of Part I, Item 1A of the Company's Annual Report on Form 10-K for the year ended December 31, 2024, which was filed with the Securities and Exchange Commission (SEC) on March 3, 2025, and subsequent SEC filings.

Forward-looking statements speak only as of the date they are made and are not guarantees of future performance. Accordingly, you should not place undue reliance on forward-looking statements. The Company does not undertake any obligation to publicly update or revise our forward-looking statements, except as required by law.

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