The study, which included a six-month open-label extension, evaluated the efficacy and safety of Adhansia XR in adults with ADHD

Stamford, Conn., March 25, 2020 – Adlon Therapeutics L.P. today announced a publication in the Journal of Attention Disorders of data from a randomized, double-blind, fixed-dose study evaluating the efficacy and safety of PRC-063 compared to placebo in a community-based adult population with Attention-Deficit/Hyperactivity Disorder (ADHD). The publication also highlights results from a six-month dose-optimized open-label extension study that enrolled patients who had completed the double-blind study. PRC-063 was approved by the U.S. Food and Drug Administration (FDA) in February 2019 for the treatment of ADHD in patients six years and older and is available as Adhansia XR^® (methylphenidate hydrochloride) extended-release capsules CII.

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

The article, “Efficacy and Safety of PRC-063, Extended-Release Multilayer Methylphenidate in Adults with ADHD Including 6-Month Open-Label Extension,” authored by Margaret D. Weiss, MD, PhD, FRCP(C); Ann C. Childress, MD; and Graeme A.E. Donnelly, MS, is available at this link.

“The publication of these data further contribute to the growing body of evidence for Adhansia XR and validate its potential to address the needs of certain ADHD patients who may require a longer treatment duration,” said Mike Ronning, vice president, sales and marketing, and general manager, Adlon Therapeutics. “This research reinforces our ongoing commitment to developing and providing treatments that address the needs of patients with ADHD.”

The double-blind study enrolled 375 adults, with 333 adults completing the study. In this study, eligible patients with a DSM-5 diagnosis of ADHD were randomly assigned to a fixed daily dose of Adhansia XR (25, 45, 70, or 100 mg) or placebo for four weeks. The primary endpoint was the between-treatment comparison of the change from baseline in ADHD Rating Scale-5 (ADHD-RS-5) total score at the end of study. The ADHD-RS-5 is a clinician administered scale evaluating 18 symptoms of ADHD on a 4-point scale of severity (0–3), with lower scores indicating less severe symptoms. Treatment response was also measured using the Clinical Global Impression Scale of Improvement (CGI-I). The CGI-I is a 7-point scale in which patients are rated from “very much improved” to “very much worse” compared with baseline behavior. Responders are defined as patients rated as “much improved” or “very much improved” using the CGI-I scale.

Following four weeks of treatment, patients receiving Adhansia XR had a greater change from baseline in ADHD-RS-5 total scores (least-square [LS] mean = −4.7 [−7.7, −1.6], p=.003) compared to patients receiving placebo. When evaluating the individual dosage groups, only the 45 mg (LS mean [95% CI] treatment difference of −6.9 [−11.5, −2.2]) and 100 mg groups (−8.1 [−12.9, −3.2]) had statistically significant between-treatment differences from placebo. Based on categorical analysis of the CGI-I score, 47.5% of patients receiving Adhansia XR were responders compared to 29.5% patients receiving placebo (p=.002, comparing ranked scores to placebo using Wilcoxon rank sum tests).

The open label extension study enrolled 184 patients who had completed the double-blind study and 124 patients completed the six-month open-label study. In this study, each patient was titrated to their optimal dose of Adhansia XR (25, 35, 45, 55, 70, 85 or 100 mg/day). Statistically significant changes on the ADHD-RS-5 total score from baseline and from end of the double-blind study were observed within one month of entering the open-label study (p<.0001) and were sustained at each monthly visit throughout the open-label study.

Participants were assessed for adverse events (AEs) throughout the double-blind and six-month open-label study. The most frequently reported AEs in the Adhansia XR and placebo groups were headache (Adhansia XR double-blind, 17.5%; Adhansia XR open-label, 10.8%; placebo, 11.5%), insomnia (Adhansia XR double-blind, 15.8%; Adhansia XR open-label, 15.1%; placebo, 3.8%), and decreased appetite (Adhansia XR double-blind, 11.1%; Adhansia XR open-label, 8.1%; placebo, 2.6%). As measured by the Pittsburgh Sleep Quality Index (PSQI) Global Scores, sleep quality for Adhansia XR was not significantly different from placebo at end of the double-blind study (p=.123).

“In this double-blind study, followed by an open-label extension among a smaller subset of eligible participants, we assessed efficacy, safety, and tolerability of this extended-release methylphenidate product on symptoms of ADHD in adults,” said Ann C. Childress, MD. “We believe these results, in combination with a study evaluating the product over 16-hours in adults, support the use of Adhansia XR, a long-acting methylphenidate product, to help treat ADHD symptoms throughout a typical adult day.”

These studies were conducted at 34 sites in the US and Canada and were executed in accordance with Good Clinical Practice (GCP) guidelines as required by the Declaration of Helsinki 1964 and all of its amendments to this date, and the International Conference on Harmonization (ICH) Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, ICH of Pharmaceuticals for Human Use.

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. is a biopharmaceutical company dedicated to developing and providing treatment options for Attention-Deficit/Hyperactivity Disorder (ADHD) and related disorders. Our initial focus is on adults and adolescents who have been diagnosed with ADHD. Adlon is a subsidiary of Purdue Pharma L.P.

For more information, please visit www.adlontherapeutics.com.

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media@54.82.90.148

Reference:

¹ Purdue Pharma L.P. Adhansia XR Full Prescribing Information. July 2019. Accessed January 2020. Retrieved from http://app.adlontherapeutics.com/adhansia-xr/fpi.pdf.