In a Market Dominated by Well-Entrenched, Effective Psychostimulants, What Do Physicians and Payers Identify as Areas for Differentiation?

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood condition that can continue through adolescence and into adulthood. The key treatment goals for pediatric and adult ADHD include controlling the core symptoms of the condition—inattention and/or hyperactivity/impulsivity—as well improving patients’ overall functioning and quality of life. Pharmacological treatment of both pediatric and adult ADHD is dominated by psychostimulants, which boast robust efficacy (research suggests and interviewed experts report that over 70% of patients respond to psychostimulant treatment) and an acceptable balance of safety and tolerability. Nonstimulant therapies are common second- or third-line treatment options; several nonstimulant therapies are available in the United States, while only one is currently available in Europe and Japan. Nevertheless, given the sizable drug-treated ADHD population (we estimate over 6.4 million drug-treated pediatric and adult patients, combined, in 2013 across the seven major markets under study), as well as the fact that there is still a proportion of patients who cannot tolerate or who do not respond adequately to currently available treatments, opportunity exists for emerging agents to achieve commercial success. Moreover, psychostimulants’ risks for abuse and dependence as well as their inability to fully alleviate secondary symptom domains such as executive functioning present areas of opportunity for emerging therapies to be differentiated from competitors.

Questions Answered in This Report:

  • Controlling the core symptoms of attention-deficit/hyperactivity disorder (ADHD)—inattention and/or hyperactivity/impulsivity—and improving global outcomes/functioning are key goals in the treatment of pediatric ADHD. What are the key primary and secondary clinical trial end points with which new therapies are evaluated? How do U.S. and European psychiatrists weight specific efficacy end points and other drug attributes in their prescribing decisions for pediatric ADHD?

  • Lisdexamfetamine (Shire’s Vyvanse/Elvanse) is the 2013 major-market sales leader for ADHD. What weaknesses exist in its profile that would allow emerging therapies to gain a foothold in the market? Have emerging therapies demonstrated to date strengths on the attributes that surveyed psychiatrists indicate are the most important in their prescribing decisions? Which emerging therapies, if any, will offer the clinical improvements over currently available therapies that surveyed MCO PDs seek from new therapies?

  • An agent’s ability to control the core symptoms of ADHD, as well as its risk for abuse and dependence are key drivers of physicians’ prescribing decisions and/or are the focus of drug development for new ADHD therapies. What trade-offs across these and other clinical attributes are U.S. psychiatrists willing to make when considering the use of emerging therapies for the treatment of pediatric ADHD? Based on the trade-offs in price and performance across key drug attributes that U.S. psychiatrists are willing to make, how do physician preference and prescribing likelihood vary across different target product profiles for pediatric ADHD?

  • Based on its clinical profile, lisdexamfetamine is the current clinical gold standard in our Drug Comparator Model. What attributes do thought leaders believe differentiate this therapy from competing current therapies and emerging therapies? Will any therapies in development challenge lisdexamfetamine as the future gold standard in 2018 or 2023?


Attributes included in conjoint analysis-based assessment of target product profiles for pediatric attention-deficit/hyperactivity disorder:

- Reduction from baseline in ADHD-Rating Scale (RS)-IV total score

- Percentage of patients attaining ‘much’ or ‘very much’ improved rating on Clinical Global Impression-Improvement (CGI-I) scale

- Incidence of serious adverse events (e.g., suicidality, psychiatric side effects, cardiac events)

- DEA drug schedule status

- Drug formulation

- Dosing frequency

- Price/day

Attributes included in assessment of U.S. payers’ receptivity to new therapies for pediatric attention-deficit/hyperactivity disorder:

- Efficacy: A nonstimulant’s effect on core ADHD symptoms (measured by point reduction on the ADHD-RS-IV total score)

- Safety: Risk for abuse and dependence (assessed by DEA drug schedule status)

- Delivery burden (dosing frequency and drug formulation)

- Efficacy: Maintenance control of ADHD symptoms (measured by the rate of treatment failures occurring once maintenance of therapy has been established)

Physicians surveyed: 61 U.S. and 32 European psychiatrists.

Payers surveyed: 22 U.S. MCO PDs.

Comprehensive List of Therapies Included in Our Research and Modeling:

Current Therapies

- Lisdexamfetamine (Shire’s Vyvanse/Elvanse)

- Methylphenidate ER (Janssen’s Concerta, generics)

- Mixed amphetamine salts ER (Shire’s Adderall XR, generics)

- Atomoxetine (Eli Lilly’s Strattera)

- Guanfacine ER (Shire’s Intuniv, generics)

Emerging Therapies

- Dasotraline (Sunovion)

- Metadoxine ER (Alcobra Pharma)

- MPH-MLR (methylphenidate extended-release multilayer bead formulation, Rhodes Pharmaceuticals)

- HLD-200 (methylphenidate-DELEXIS, Highland Therapeutics)

- NT-0202 (amphetamine-based ODT [orally disintegrating tablet], Neos Therapeutics)