FDA Approves Supplemental New Drug Application for Adhansia XR® (methylphenidate HCl) Extended-Release Capsules CII

Phase 3 Adult Laboratory Classroom study confirmed that Adhansia XR provided rapid and sustained symptom relief for up to 16 hours in adults diagnosed with ADHD with a safety profile similar to current approved stimulants for the treatment of ADHD

STAMFORD, Conn.--(BUSINESS WIRE)--Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P., announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to update the prescribing information for Adhansia XR® (methylphenidate hydrochloride) extended-release capsules CII. Adhansia XR® was approved by FDA for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older in February 2019.

The sNDA approval was based on data from a randomized, double-blind, parallel-group, placebo-controlled, Phase 3 Adult Laboratory Classroom (ALC) study evaluating the safety and efficacy of Adhansia XR in adult patients diagnosed with ADHD. The efficacy assessment evaluated Adhansia XR compared to placebo as measured by Permanent Product Measure of Performance-Total (PERMP-T) scores assessed during the full-day ALC study. The PERMP is a skill adjusted math test commonly used in classroom studies with ADHD patients. It stresses attention and measures the patient’s ability to initiate a task, complete written seat work, and stay on task (i.e., their ability to sustain attention).

The Full Prescribing Information for Adhansia XR contains a Boxed Warning emphasizing that CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse and dependence. Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy.¹

Post-washout, patients were dose-optimized on Adhansia XR (25-100 mg/day) over seven weeks before randomization to continue their optimal dose of Adhansia XR or placebo for a one-week double-blind treatment period which ended with one full-day evaluation in an ALC. Average test scores during the full-day ALC visit demonstrate statistically significant improvement in ADHD symptoms in patients treated with Adhansia XR (n=121) compared to patients receiving placebo (n=118) [LS mean difference (95% CI): 16.3 (7.6, 24.9); p= 0.0003]and this improvement was observed at every individual timepoint from one hour up to and including 16 hours (all p<0.05).

During the open label dose‑optimization period, 73% experienced ≥1 treatment-related adverse events (TEAEs). The most frequently reported TEAEs were headache (21%), decreased appetite (21%), and insomnia (16%). Most TEAEs were of mild or moderate intensity. No correlation was observed between dose level and incidence of TEAEs.

“As a research-driven organization, we are committed to ongoing evaluation of our medicines as part of addressing the current and future needs of individuals diagnosed with ADHD,” said Julie Ducharme, BPharm, MSc, PhD, vice president and chief scientific officer, Purdue Pharma. “We are pleased to share the news of this label update for Adhansia XR and believe inclusion of the ALC study is relevant for certain patients who may require a fast onset and longer treatment duration.”

Adhansia XR is the only extended-release stimulant that provides an onset of action at 1 hour and duration of clinical effect throughout the day (up to 16 hours in adults) with a single daily dose. Adhansia XR® capsules contain identical beads which are formulated using the proprietary smart design MLR™ (Multi-Layer Release) technology.

Adhansia XR is not appropriate for all patients, and healthcare professionals should work with their patients to determine the most appropriate treatment option. Additionally, Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or product components, as well as patients receiving concurrent treatment with a monoamine oxidase inhibitor (MAOI) or who have used an MAOI within the preceding 14 days.¹

The Full Prescribing Information for Adhansia XR, including Boxed Warning, is available at this link. Please see Important Safety Information for Adhansia XR below, including the Boxed Warning, Contraindications, Warnings and Precautions including the potential for abuse and dependence, serious cardiovascular events, blood pressure and heart rate increases, psychiatric adverse reactions, priapism, peripheral vasculopathy, long-term suppression of growth, allergic-type reactions, and Adverse Reactions.¹

About Adhansia XR®
Adhansia XR was developed by Purdue Pharma (Canada). The medication was granted marketing authorization from Health Canada in December 2017 and is currently marketed in Canada as FOQUEST™ for the treatment of ADHD. In the U.S., the medication was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older in February 2019.

Adhansia XR capsules contain multilayered beads, which are composed of an immediate-release layer which contains approximately 20 percent of the methylphenidate dose, and a controlled-release layer which contains approximately 80 percent of the methylphenidate dose, for oral administration. The MLR™ (multi-layer release) technology is a controlled-release delivery system patented by Purdue Pharma.

Please see Important Safety Information, including Boxed Warning, Warnings & Precautions, and Adverse Reactions below.

IMPORTANT SAFETY INFORMATION¹

CONTRAINDICATIONS

Adhansia XR^® is contraindicated in patients with a known hypersensitivity to methylphenidate or other components of Adhansia XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products. Adhansia XR is also contraindicated in patients receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a MAOI, because of the risk of hypertensive crisis.

WARNINGS AND PRECAUTIONS

Potential for Abuse and Dependence

CNS stimulants, including Adhansia XR, 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.

Serious Cardiovascular Events

Sudden death, stroke and myocardial infarction have occurred in adults treated with CNS stimulant treatment at recommended doses. Sudden death has occurred in pediatric patients with structural cardiac abnormalities and other serious cardiac problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Adhansia XR treatment.

Blood Pressure and Heart Rate Increases

CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.

Psychiatric Adverse Reactions

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients 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).

CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Adhansia XR. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0% in placebo-treated patients.

Priapism

Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products, in both pediatric and adult patients. Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. Priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Peripheral Vasculopathy, including Raynaud’s Phenomenon

CNS stimulants, including Adhansia XR, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Long-Term Suppression of Growth

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development.

Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Adhansia XR. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Allergic-Type Reactions FD&C Yellow No. 5

Adhansia XR 45 mg capsules contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity.

ADVERSE REACTIONS

The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in adults are insomnia, dry mouth, and decreased appetite.

The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in pediatric patients are decreased appetite, insomnia, weight decreased, and upper abdominal pain.

PREGNANCY EXPOSURE REGISTRY

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Adhansia XR during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.

To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please read the Full Prescribing Information, including Boxed Warning.

About Adlon Therapeutics L.P.
Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P., is a specialty pharmaceutical company committed to providing treatment options for patients who suffer from the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). Our mission is to serve patients and the ADHD community by developing innovative medicines and supporting responsible prescription stimulant utilization through awareness, research, and supporting policies that align with the appropriate diagnosis and treatment of ADHD. For more information, please visit www.adlontherapeutics.com or follow us on Twitter and LinkedIn.

Reference:
¹ Purdue Pharma L.P. Adhansia XR Full Prescribing Information. July 2019. Accessed May 2021. Retrieved from http://app.adlontherapeutics.com/adhansia-xr/fpi.pdf.

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