Azstarys (serdexmethylphenidate/dexmethylphenidate oral) / Zevra Therap, Commave Therap, Corium, Ark Biosci - LARVOL DELTA

ArkBio Announces the Completion of Phase III Clinical Study for AK0901 in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD) in China (PRNewswire-Asia) - P3 | N=55 | CTR20240367 | "Shanghai Ark Biopharmaceutical...announced the successful completion of the Phase III clinical study of AK0901, a novel drug for the treatment of attention deficit hyperactivity disorder (ADHD). This milestone represents a substantial step forward for ArkBio in the research and development of drugs for pediatric psychiatric disorders, potentially offering new treatment options and improved therapeutic outcomes for children with ADHD in China....The Phase III clinical study of AK0901 in China was led jointly by Beijing Anding Hospital affiliated with Capital Medical University and Peking University Sixth Hospital, with the participation of eight clinical centers nationwide...The study results met both primary and key secondary endpoints and reached statistical significance in all the visiting time points compared to placebo, which provides a strong scientific basis for future treatment of Chinese ADHD patients."

P3 data • Trial completion • Attention Deficit Hyperactivity Disorder

Duration and Efficacy of Azstarys on Adult ADHD Symptoms and Executive Function in Early Evening (clinicaltrials.gov) - P4 | N=29 | Completed | Sponsor: NYU Langone Health | Recruiting ➔ Completed | Trial completion date: Feb 2025 ➔ Jul 2024 | Trial primary completion date: Dec 2024 ➔ Jul 2024

Trial completion • Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

KP415P02: A Safety/Tolerability and PK Study With Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=123 | Active, not recruiting | Sponsor: Corium, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

KP415P01: An Efficacy and Safety Study w/ Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=246 | Completed | Sponsor: Corium, Inc. | Active, not recruiting ➔ Completed

Trial completion • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

SAFETY AND EFFICACY OF KP1077 IN A PHASE 2, DOUBLE-BLIND, RANDOMIZED TRIAL IN PATIENTS WITH IDIOPATHIC HYPERSOMNIA (SLEEP 2024) - "The active ingredient in KP1077 is serdexmethylphenidate (SDX), a prodrug of d-methylphenidate. KP1077 was well-tolerated in patients with IH with AEs typical for a central nervous system stimulant. Meaningful clinical improvements of EDS, sleep inertia and brain fog were observed after 5 weeks of OL KP1077."

Clinical • P2 data • CNS Disorders • Excessive Daytime Sleepiness • Insomnia • Pain • Psychiatry • Sleep Disorder • Suicidal Ideation

KP415P01: An Efficacy and Safety Study w/ Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=246 | Active, not recruiting | Sponsor: Corium, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Study to Evaluate the Efficacy, Safety and Tolerability of Oral AK0901 in Children With ADHD (clinicaltrials.gov) - P3 | N=50 | Not yet recruiting | Sponsor: Shanghai Ark Biopharmaceutical Co., Ltd.

New P3 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Serdexmethylphenidate/dexmethylphenidate for children with attention-deficit/hyperactivity disorder: dose optimization from a laboratory classroom study. (PubMed, Front Psychiatry) - "SDX/d-MPH demonstrated significant reductions in ADHD severity in children based on the Conners 3rd Edition-Parent scores. Determining the optimal dosage of SDX/d-MPH and its effect on ADHD severity could enable the development of a more clinically relevant treatment regimen in children with ADHD."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

KP415P01: An Efficacy and Safety Study w/ Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=230 | Recruiting | Sponsor: Corium, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

KP415P02: A Safety/Tolerability and PK Study With Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: Corium, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Stimulant prodrugs: A pharmacological and clinical assessment of their role in treating ADHD and binge-eating disorder. (PubMed, Adv Pharmacol) - "Lisdexamfetamine (LDX; prodrug of d-amphetamine) is approved to treat both ADHD and BED. Serdexmethylphenidate (SDX; prodrug of d-threo-methylphenidate) is not clinically approved as monotherapy but, in a fixed-dose combination with immediate release d-threo-methylphenidate (Azstarys™), SDX is approved for managing ADHD in children/adolescents...The chemical, pharmacological and PK/PD properties responsible for the therapeutic actions of the prodrugs, LDX and SDX, are compared and contrasted. Finally, we critically assess their contribution as ADHD and BED medications, including advantages over their respective active metabolites, d-amphetamine and d-threo-methylphenidate, and also their potential for misuse and abuse."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Binge Eating Disorder • CNS Disorders • Mental Retardation • Psychiatry

Duration and Efficacy of Azstarys on Adult ADHD Symptoms and Executive Function in Early Evening (clinicaltrials.gov) - P4 | N=30 | Recruiting | Sponsor: NYU Langone Health | Not yet recruiting ➔ Recruiting

Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Duration and Efficacy of Azstarys on Adult ADHD Symptoms and Executive Function in Early Evening (clinicaltrials.gov) - P4 | N=30 | Not yet recruiting | Sponsor: NYU Langone Health

New P4 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Chromatographic reversed HPLC and TLC-densitometry methods for simultaneous determination of serdexmethylphenidate and dexmethylphenidate in presence of their degradation products-with computational assessment. (PubMed, BMC Chem) - "They were successfully applied for quantitation of SER.DMP and DMP in pure and capsule forms. The results were statistically compared with those obtained by the reported method in terms of accuracy, precision and robustness, and no significant difference was found."

Journal

Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder. (PubMed, Front Psychiatry) - P3 | "In this analysis of children taking SDX/d-MPH for ADHD, sleep problems did not worsen based on the mean CSHQ total sleep disturbance score. Statistically significant improvements in most CSHQ sleep domains were observed after 1 month and lasted for up to 12 months of treatment."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mood Disorders • Psychiatry • Sleep Disorder

"These include brand name (= Generic version): - @VYVANSE (Lisdexamfetamine) - Concerta, Ritalin LA, Daytrana, etc (Methylphenidate) - Focalin ER (Dexmethylphenidate ER) @Novartis - Adderall XR - Dexedrine, etc (Dextroamphetamine) - Azstarys These last 12 hours or longer" (@RTorof)

Evaluating serdexmethylphenidate and dexmethylphenidate capsules as a once-daily treatment option for ADHD. (PubMed, Expert Opin Pharmacother) - "Although the research is relatively limited thus far, early data suggests it to be a safe medication to consider with side effects being similar to other stimulant medications. Its prodrug design is useful in potentially serving as a deterrent to intentional parental abuse and its ability to be opened and sprinkled makes it an option for those individuals with ADHD who might be unable to swallow pills."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Behavior Disorders • CNS Disorders • Mental Retardation • Psychiatry

Analysis of Growth Velocity in Children with Attention-Deficit/Hyperactivity Disorder Treated for up to 12 Months with Serdexmethylphenidate/Dexmethylphenidate. (PubMed, J Child Adolesc Psychopharmacol) - P3 | " The overall effects of SDX/d-MPH on growth velocity (the change in weight and height from one time point to the next) were minimal, and the range of changes was not considered clinically significant. ClinicalTrials.gov identifier: NCT03460652."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

A Comprehensive Review of Novel FDA Approved Psychiatric Indications From 2018-2022 (APA 2023) - "In 2019, Zulresso (brexanolone) was approved for postpartum depression, Caplyta (lumateperone) for schizophrenia, and Dayvigo (lemborexant) for insomnia. Azstarys (serdexmethylphenidate/dexmethylphenidate) and Qelbree (viloxazine) were both FDA approved in 2021 for ADHD. The newest FDA approvals include Quvivig (daridorexant) for insomnia and Auvelity (dextromethorphan/bupropion) for major depressive disorder... We found 8 novel psychiatric indications out of 226 total pharmaceuticals approved by the US Food and Drug Administration within the years of 2018 and 2022, representing 3.5% of total FDA approvals during that time period. Clinical trials for each medication suggested favorable results in Phase III trials that lead to approval, along with current success in Phase IV trials as well. In 2018, Lucemyra (lofexidine) was approved for the treatment of opioid withdrawal."

FDA event • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Developmental Disorders • Insomnia • Major Depressive Disorder • Mental Retardation • Mood Disorders • Postpartum Depression • Psychiatry • Schizophrenia • Sleep Disorder

Safety and Tolerability of Serdexmethylphenidate/Dexmethylphenidate Capsules in Children with Attention-Deficit/Hyperactivity Disorder: A 12-Month, Open-Label Safety Study. (PubMed, J Child Adolesc Psychopharmacol) - P3 | "SDX/d-MPH also showed sustained efficacy during the 1-year treatment period. ClinicalTrials.gov identifier: NCT03460652."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Infectious Disease • Psychiatry • Respiratory Diseases

KemPharm Announces Corporate Name Change to Zevra Therapeutics (GlobeNewswire) - “KemPharm, Inc…announced today that it changed its name to Zevra Therapeutics, Inc. (‘Zevra’). This name change reflects the Company’s intensified focus and dedication to developing transformational, patient-focused therapies for rare diseases with limited or no treatment options. In conjunction with the name change, the Company will begin trading under the new ticker symbol ‘ZVRA’ on The Nasdaq Global Market on or about March 1, 2023….Zevra looks ahead to key milestones in 2023, including the resubmission of arimoclomol New Drug Application (‘NDA’) to the FDA as early as Q3 2023…and the potential achievement of certain commercial sales milestones for our partnered asset, AZSTARYS^®.”

Commercial • NDA • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

"Azstarys looking meaningful with backups?" (@Adasiu1978)

KP415P02: A Safety/Tolerability and PK Study With Azstarys® in Children With ADHD (clinicaltrials.gov) - P4 | N=100 | Not yet recruiting | Sponsor: Corium, Inc.

New P4 trial • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) Optimized Dose Levels and Effects on Attention-deficit/hyperactivity Disorder-rating scale-5 (ADHD-RS-5) Response Rates in Children with ADHD (AAP-NCE 2022) - P3 | "This analysis showed that responders are evident after the first week of treatment at the 26.1-/5.2-mg and 39.2-/7.8-mg final dose levels, with small increases in the proportion of responders thereafter, whereas the 52.3-/10.4-mg final dose level continued to notably increase in the proportion of responders after titration to the 52.3-/10.4-mg final dose level."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Dose Proportionality and Steady-State Pharmacokinetics of Serdexmethylphenidate/Dexmethylphenidate, a Novel Prodrug Combination to Treat Attention-Deficit/Hyperactivity Disorder. (PubMed, J Child Adolesc Psychopharmacol) - " The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional C and AUC across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment."

Journal • PK/PD data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry