Corium's Novel ADHD Medication AZSTARYS® (serdexmethylphenidate and dexmethylphenidate) Shown Safe and Effective in Long-Term Study

Significant improvement in symptoms and well-tolerated safety profile through 12 months of treatment

Reinforces prior data demonstrating AZSTARYS is safe and effective

BOSTON, Feb. 22, 2023 /PRNewswire/ -- Corium, LLC, a commercial-stage biopharmaceutical company leading the development and commercialization of novel central nervous system (CNS) therapies, announced today publication of the results from a 12-month, open-label, phase 3 safety study of AZSTARYS (serdexmethylphenidate [SDX] and dexmethylphenidate [d-MPH]), which is indicated for treatment of attention-deficit hyperactivity disorder (ADHD) in people ages six and older. Published in the peer-reviewed Journal of Child and Adolescent Psychopharmacology (JCAP), the results show that AZSTARYS provided sustained symptom improvement and was well-tolerated in children aged 6 to 12 who participated in the study. AZSTARYS was approved by the U.S. FDA in March 2021 and has recently been launched nationally by Corium.

"This second phase 3 trial of AZSTARYS in children 6 to 12 years of age adds to the safety and tolerability data from an earlier four-week pivotal efficacy study," said Ann Childress, M.D., lead author of the study article, president of the Center for Psychiatry and Behavioral Medicine, and lead investigator. "The results of this long-term study showed that AZSTARYS is safe, well tolerated, and demonstrated continued efficacy during a year-long treatment period and is an important treatment option for persons with ADHD."  

"Once-daily AZSTARYS demonstrated sustained control of ADHD symptoms in children treated for an entire year with a side effect profile similar to other methylphenidate products," said Charles Oh, M.D., Chief Medical Officer of Corium. "This long term study reinforces the efficacy and safety of AZSTARYS as an important treatment option for healthcare professionals to consider when choosing the optimal ADHD therapy for their patients."

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 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

The long-term study^¹ (NCT03460652) builds on a previously-reported pivotal double-blind, one-month, laboratory classroom-based efficacy study^² (NCT03292952) of children ages 6 to 12 years with ADHD comparing AZSTARYS to a placebo. The one-month trial demonstrated AZSTARYS significantly improved ADHD symptoms with a well-tolerated safety profile.

This year-long, open-label safety study of AZSTARYS enrolled 282 children aged 6 to 12 years in the U.S., 70 who previously enrolled in the one-month efficacy trial and 212 new study participants. After screening and a three-week dose-optimization phase for new participants, 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.

AZSTARYS Shown to Be Safe, Well-Tolerated, and Effective by Producing 70 Percent Average ADHD Symptom Improvement in Trial

Safety and Tolerability

Of the 282 children enrolled in the study, 254 entered the 12-month treatment phase, and 155 completed the study. Reasons for discontinuing the study prior to completion included loss to follow-up (51), withdrawal of consent (28), noncompliance (17), adverse events (11), lack of efficacy (2), protocol deviation (1), and other reasons (17). The treatment-phase safety assessments included 238 children who received one or more AZSTARYS doses and had one or more post-dose safety assessments.

After one year of AZSTARYS treatment, 60.1 percent (143) of the children experienced at least one treatment-emergent adverse event (TEAEs), including 131 children with mild to moderate TEAEs and 12 children with severe TEAEs. Six children (2.5 percent) discontinued the study due to a TEAE during the treatment phase. There were no life-threatening TEAEs and no deaths reported during the study. The most common TEAEs during the treatment phase were decreased appetite (18.5 percent), upper respiratory tract infection (9.7 percent), nasopharyngitis (8.0 percent), decreased weight (7.6 percent), irritability (6.7 percent), and increased weight (5.0 percent).  

Two subjects had eight serious TEAEs that were unrelated to study treatment. Because MPH products are associated with increased blood pressure and heart rate, study investigators monitored both throughout the study. There were no clinically meaningful trends in electrocardiograms, cardiac events, or blood pressure events, and none led to discontinuation.

While AZSTARYS has not been studied in any head-to-head comparison studies, Dr. Childress and her co-investigators noted in the article that changes in children's weight, height, and sleep patterns and the incidence of TEAEs with AZSTARYS treatment were comparable or lower than those reported for other MPH products approved for the treatment of children with ADHD. Also, in general, this long-term study had fewer children discontinuing the study due to TEAEs than those reported in other MPH studies. MPH is the most-commonly prescribed medication for the treatment of children with ADHD because of its known ability to mitigate core symptoms of ADHD in children and its overall favorable safety record.

Symptom Improvement

At study initiation, the children had mean (±SD) ADHD Rating Scale-5 (ADHD-RS-5) scores of 41.5 (±7.7). After their first month of AZSTARYS treatment, the children scored on average 16.1 (±10.3), a decline of -25.3 (±12.1; p < 0.001). After one year of treatment the children's ADHD symptoms significantly improved as demonstrated by an approximate 70 percent decrease from baseline.

Similarly, the children significantly improved in the clinical severity of their ADHD symptoms as assessed by the Clinical Global Impressions–Severity (CGI-S) scale. At the study start, the children averaged 4.7 (± 0.7) on the CGI-S scale but their scores decreased after one month of AZSTARYS treatment to average 2.5 (±1.1), a decline of -2.2 (±1.1; p < 0.0001). Their average CGI-S scale scores remained in the 2.2 to 2.4 range for the remainder of the study.

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 www.fda.gov/medwatch, 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 https://www.corium.com/.

Reference

1. Childress AC, Marraffino A, Cutler AJ, et al. Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study.  J Child Adolesc Psychopharmacol. 2023. Ahead of print https://www.liebertpub.com/doi/10.1089/cap.2022.0076.   
2. Kollins SH, Braeckman R, Guenther S, et al. A Randomized, Controlled Laboratory Classroom Study of Serdexmethylphenidate and d-Methylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2021;31(9):597-609. doi:10.1089/cap.2021.0077.

Contact:
Corium, LLC
[email protected] 
202-413-4226

SOURCE Corium, LLC

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