From a trickle to a flood: Pipelines fill with psychotropics for children

• were required to review existing data for using their drugs in a pediatric population
  
• could extrapolate efficacy data from adults to children, if the course of disease and effects of drug treatment were sufficiently similar in adult and pediatric patients and if appropriate pharmacokinetic and safety data were provided for younger patients.
  

FDAMA. The FDA’s next step was included in the FDA Modernization Act (FDAMA) of 1997, which allowed the agency to ask pharmaceutical manufacturers to generate safety and effectiveness data for drugs likely to be used in pediatrics. In exchange, manufacturers received 6 months’ marketing exclusivity (in addition to existing patent protection) for those drugs.

Many companies did sponsor additional safety and efficacy studies, although the incentive’s structure clearly favored drugs with high sales volume. For example, consider two products with annual sales of $200 million and $800 million, respectively. Six months of exclusive marketing rights would generate $400 million in additional revenue from the $800 million product—double the annual revenue of the $200 million product. The pharmaceutical company could obtain this benefit even if total pediatric use were quite small because the 6 months of exclusivity applied to all product sales, including pediatric and adult use.

The FDAMA had several other weaknesses:

• A manufacturer could obtain its benefit even if studies failed to demonstrate the product’s efficacy in the pediatric population.
  
• The regulation provided no incentive to develop pediatric data for drugs that had lost patent protection.
  
• It did not induce pharmaceutical companies to include pediatric studies early in drug development.
  

• for all new chemical entities (drugs in development and not yet approved)
  
• and for development programs seeking new indications, dosage forms, treatment regimens, or routes of administration for approved products.
  

Box 2

Drugs in development

As a result of these regulatory changes, the Pharmaceutical Research and Manufacturers of America (PhRMA) reports that nearly 200 drugs and vaccines are in development for children, (Box 2). In addition to the 11 drugs identified by PhRMA for treating psychiatric disorders in children and adolescents, at least another 10 were in the pipeline through the first 6 months of 2002 (Table).¹¹ By the time you read this, some of the drugs may have been terminated from development, new drugs may have been added, and others will have emerged from the development process to receive FDA approval for pediatric use.

Indications. Among the 21 compounds listed in development for 10 different psychiatric indications, 16 are already approved for adult use. One—donepezil—is marketed for management of Alzheimer’s dementia symptoms, but for children and adolescents the agent is being developed for treatment of attention-deficit/hyperactivity disorder (ADHD).

Four other approved drugs appear to be in development for new indications, including mania (topiramate), autism (secretin), Tourette’s syndrome (mecamylamine), and ADHD (modafinil). Among the five new chemical entities (NCEs—investigational drugs not yet marketed with any indication), four appear to be in development for ADHD and one for a disorder of childhood listed only as behavioral disorders.

Table

PSYCHOTROPICS IN DEVELOPMENT FOR CHILDREN AND ADOLESCENTS, LISTED BY INDICATION