Corium's Novel ADHD Medication AZSTARYS® (Serdexmethylphenidate and Dexmethylphenidate) Had No Clinically Significant Impact on Children's Weight and Height Growth Rate

2023-05-22

临床结果临床3期上市批准临床2期

New analysis from long-term study published in Journal of Child and Adolescent Psychopharmacology Reinforces prior data demonstrating AZSTARYS, first and only medicine of its kind, is effective and safe BOSTON , May 22, 2023 /PRNewswire/ -- Corium, LLC, a commercial-stage biopharmaceutical company leading the development and commercialization of novel central nervous system (CNS) therapies, announced that an analysis of a long-term, 12-month, open-label Phase 3 study of children aged 6-12 using its novel attention-deficit hyperactivity disorder (ADHD) medication AZSTARYS (serdexmethylphenidate [SDX] and dexmethylphenidate [d-MPH]) showed no clinically significant impact on weight and height growth rate in pediatric patients. CNS stimulants prescribed for treatment of ADHD have been associated with slowing of height and weight growth in pediatric patients. The study results were published in the peer-reviewed Journal of Child and Adolescent Psychopharmacology (JCAP). "This growth analysis in children, showing no clinically significant impact, addresses important considerations about height and weight growth when prescribing a stimulant such as AZSTARYS," said Ann Childress, M.D., lead author of the study article, president of the Center for Psychiatry and Behavioral Medicine, and lead investigator. "This analysis builds on previous analyses of year-long treatment using SDX/d-MPH that document the medicine delivers safe, well-tolerated, and continued reduction of ADHD symptoms." "This year-long data showing the absence of a clinically significant impact on growth rate for children aged 6-12 adds an important dimension to our understanding of AZSTARYS," said Charles Oh, M.D., Chief Medical Officer of Corium. "This new analysis strengthens the pro AZSTARYS as an important treatment option for safe, effective, and sustained ADHD symptom control that clinicians, parents and patients should consider." AZSTARYS is the first and only medicine indicated for the treatment of ADHD in patients ages 6 years through adulthood that contains SDX, the prodrug of d-MPH, along with immediate-release d-MPH. SDX is a prodrug designed to be pharmacologically inactive until reaching a patient's lower gastrointestinal tract where, by design, it gradually converts to d-MPH throughout the day. This formulation provides rapid control of ADHD symptoms with the immediate-release d-MPH and extended duration of symptom control with the SDX. AZSTARYS is a Schedule II controlled substance, given it contains 30% immediate release d-MPH. The SDX component of AZSTARYS (comprising 70% of the active ingredient) is a Schedule IV controlled substance. Trial Overview This analysis used data from 238 children aged 6 to 12 years enrolled in the year-long, open-label safety study of AZSTARYS (NCT03460652) conducted in the U.S. After dose-optimization, the children received once-daily AZSTARYS doses of 26.1/5.2 milligrams (mg), 39.2/7.8 mg, or 52.3/10.4 mg of SDX/d-MPH. At enrollment, the children averaged (±standard deviation [SD]) 9.1 (±1.9) years in age and 60.9% were male. Their weight ranged from 21.0 to 97.0 kilograms (kg), averaging (±SD) 38.6 (±13.9) kg, with an average (±SD) body-mass index (BMI) of 19.2 (±4.6) kg/m2. They ranged in height from 113.5 to 171.2 centimeters (cm), averaging (±SD) 139.6 (±11.9) cm. Using weight and height measures, the investigators calculated monthly differences for the children during treatment. Using a standard calculation known as a Z-score, they also determined if the children's average weight and height differed from a general population, using 2020 growth chart data of people aged 2 to less than 20 years from the U.S. Centers for Disease Control and Prevention. A change in a Z-score that is greater than 0.5 is considered clinically significant. Expected Weight The children's weight experienced a transient decrease, followed by a slower-than-predicted gain in their first three months of treatment, yet did not significantly differ from the reference population. In the study, the difference between the children's actual weights compared to predicted body weights remained fairly constant until their treatment ended. At 90 treatment days, their average weight of 38.5 kg differed from a predicted weight of 40.2 kg by 1.7 kg. After 360 days of treatment, their weight and predicted weights averaged 41.1 kg and 42.8 kg, respectively, with the same difference as before. The change in their average (±SD) weight Z-score from the study start to 12 months was −0.20 (±0.5) and did not reach the -0.5 threshold for clinical significance. Expected Height Growth The children's height increased steadily during the study. Their increases were less than the reference population but in a range considered not clinically significant. At 90 treatment days, their average height of 140.8 cm differed from a predicted height of 141.4 cm by 0.6 cm. After 360 days of treatment, their height and predicted heights averaged 143.4 cm and 144.8 cm, respectively, a difference of 1.4 cm. The change in their average (±SD) height Z-score from the study start to 12 months was −0.21 (±0.39) and did not reach the -0.5 threshold for clinical significance. About AZSTARYS AZSTARYS, approved for patients ages 6 years through adulthood, is the first and only once-daily treatment for ADHD symptoms containing SDX, the prodrug of d-MPH. SDX is designed specifically to be pharmacologically inactive until reaching a patient's lower gastrointestinal tract, where, by design, the prodrug gradually converts to d-MPH throughout the day. This formulation provides control of ADHD symptoms both rapidly with the immediate-release d-MPH and for an extended duration with SDX. Once-daily AZSTARYS is available in the U.S. in three SDX/d-MPH dose strengths of 26.1/5.2 mg, 39.2/7.8 mg, and 52.3/10.4 mg. Indication and Important Safety Information for AZSTARYS (serdexmethylphenidate and dexmethylphenidate) INDICATION AZSTARYS is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients aged 6 years and older. IMPORTANT SAFETY INFORMATION WARNING: ABUSE AND DEPENDENCE CNS stimulants, including AZSTARYS, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. CONTRAINDICATIONS Known hypersensitivity to serdexmethylphenidate, methylphenidate, or other product components. Bronchospasm, rash, and pruritus have occurred with AZSTARYS. Hypersensitivity reactions such as angioedema and anaphylactic reactions have occurred with other methylphenidate products. Concomitant treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days, because of the risk of hypertensive crisis. WARNINGS AND PRECAUTIONS Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported at recommended doses. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, coronary artery disease, or other serious heart problems. CNS stimulants cause an increase in blood pressure and heart rate. Monitor all patients for hypertension and tachycardia. Exacerbation of Pre-existing Psychosis: May exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder: May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, or depression). New Psychotic or Manic Symptoms: At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a history of psychotic illness or mania. Discontinue if symptoms occur. Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed. CNS stimulants, including AZSTARYS, are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Carefully observe patients during treatment for digital changes. Further evaluation may be required, including referral. CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Monitor height and weight at appropriate intervals in pediatric patients. Treatment may need to be interrupted in children not growing or gaining weight as expected. ADVERSE REACTIONS Based on accumulated data from other methylphenidate products, the most common (>5 percent and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. DRUG INTERACTIONS Adjust dosage of antihypertensive drug as needed. Monitor blood pressure. Avoid use of AZSTARYS on the day of surgery if halogenated anesthetics will be used. For additional safety information, click here for Prescribing Information and Medication Guide, including BOXED WARNING. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit or call 1-800-FDA-1088. About Corium Corium, LLC, is a commercial-stage biopharmaceutical company that is leading the development and commercialization of CNS therapies that provide physicians with innovative treatment options for patients, their families, and their caregivers. Corium is commercializing two FDA approved products, ADLARITY and AZSTARYS. For further information, please visit . References 1Childress AC, Cutler AJ, Patel M, Oh C. Analysis of Growth Velocity in Children With Attention-Deficit/Hyperactivity Disorder Treated for up to 12 Months With Serdexmethylphenidate/dexmethylphenidate. J Child Adolesc Psychopharmacol. 2023. Ahead of print . Contact: Corium, LLC Gartmanpr@gmail.com 202-413-4226