AVDL Avadel Pharmaceuticals PLC

Avadel Pharmaceuticals plc (Nasdaq: AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, today announced the publication of results of a post-hoc analysis from the completed pivotal Phase 3 REST-ON clinical trial demonstrating greater weight loss in patients who received LUMRYZ compared with placebo. The paper, titled “Weight Loss With Once-nightly Sodium Oxybate for the Treatment of Narcolepsy: Analysis From the Phase III Randomized study Evaluating the efficacy and SafeTy of a ONce nightly formulation of sodium oxybate (REST-ON) Trial,” was published online in Clinical Therapeutics.

“Obesity is a struggle for many people, and it is very common in patients with narcolepsy,” said Asim Roy, M.D., co-author of the paper and Medical Director of the Ohio Sleep Medicine Institute. “Obesity is an important modifiable risk factor for cardiovascular diseases. These new data show that LUMRYZ use was associated with a reduction in body mass index and weight during the 13-week trial. While all REST-ON participants, including both narcolepsy Type 1 (with cataplexy) and narcolepsy Type 2 (without cataplexy) showed improvement in core narcolepsy symptoms (i.e., excessive daytime sleepiness and cataplexy), this improvement was even more pronounced in the subgroup experiencing a ≥5% weight loss.”

REST-ON is a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial evaluating once-at-bedtime LUMRYZ in adults with narcolepsy. Weight and body mass index (BMI) were measured at baseline and at the end of the study. The mean age of the study participants was 31.2 years, 67.9% were women and 75.5% were white. Among those treated with LUMRYZ (n=107), 67.5% and 37.0% of participants with narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2), respectively, were overweight or obese at baseline, as were 69.5% and 61.0%, respectively, of those in the placebo group (n=105). Mean weight at baseline was similar between the LUMRYZ and placebo groups (81.2 kg and 82.1 kg, respectively).

“Given the high rates of obesity in the U.S, and its associated cardiometabolic risks, we were encouraged to see that nearly one in five study participants treated with LUMRYZ experienced clinically meaningful weight loss,” said Jennifer Gudeman, Pharm.D., Senior Vice President, Medical and Clinical Affairs of Avadel. “These findings suggest that LUMRYZ, given its proven benefit in reducing cataplexy and EDS, as well its once-at-bedtime dosing, which provides the opportunity for an uninterrupted night sleep, has the potential to provide a more tailored treatment approach for people with narcolepsy who are overweight or living with obesity.”

Results of the post-hoc analysis, which evaluated the effect of LUMRYZ treatment on weight in adults with narcolepsy and further characterized participants experiencing >5% weight loss, showed:

• Participants who received LUMRYZ lost a mean of 1.3 kg from baseline to week 13. In contrast, those receiving placebo experienced a mean weight gain of 0.2 kg.
• A significantly higher proportion of study participants receiving LUMRYZ experienced ≥5% weight loss than those who received placebo (17.8% versus 3.8%; p=0.001).
• A significant reduction in BMI was observed after 13 weeks of treatment with LUMRYZ versus placebo, with a between-group difference in least squares mean change from baseline of −0.59 kg/m2 (p=0.001).
• In the weight loss group, participants shifted from obese into overweight, and from overweight into normal weight during this trial; no participants were underweight.

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

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.

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.

INDICATIONSLUMRYZ (sodium oxybate) for extended-release oral suspension is a prescription medicine used to treat the following symptoms in adults with narcolepsy:

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

It is not known if LUMRYZ is safe and effective in people less than 18 years of age.

Do not take LUMRYZ if you take 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 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 have or had depression or have tried to harm yourself. Call your doctor right away if you have symptoms of mental health problems or a change in weight or appetite.
• Sleepwalking. Sleepwalking can cause injuries. Call your doctor if you start sleepwalking.

Tell your doctor if you are on a salt-restricted diet or if you 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. 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 plcAvadel 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 excessive daytime sleepiness (EDS) in adults with narcolepsy. For more information, please visit www.avadel.com.

Cautionary Disclosure Regarding Forward-Looking StatementsThis 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 potential therapeutic benefit of LUMRYZ in treating narcolepsy-related EDS or cataplexy, including potential impact on patient weight; and the results and analysis of the Phase 3 REST-ON trial, including the details and content thereof. 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, 2023, which was filed with the Securities and Exchange Commission (SEC) on February 29, 2024, 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.

Investor Contact:Courtney MogerleyPrecision AQCourtney.Mogerley@precisionAQ.com(212) 698-8687

Media Contact:Lesley StanleyReal Chemistrylestanley@realchemistry.com (609) 273-3162