Shire and its newly acquired subsidiary—New River
Pharmaceuticals—won final approval from the U.S. Food and Drug
Administration (FDA) last month to market lisdexamfetamine (Vyvanse) for
treatment of attention-deficit/hyperactivity disorder (ADHD) in children and
adolescents aged 6 to 12.
Shire CEO Matthew Emmens said in a press release that the new medication
should start showing up on pharmacy shelves in the second quarter of 2007.
Lisdexamfetamine is a prodrug composed of the amino acid L-lysine bound to
the amino group of the therapeutically active ingredient d-amphetamine. When
taken orally, the therapeutic effects characteristic of amphetamine are
blocked by the conjugated amino acid. However, when the prodrug is absorbed
from the gastrointestinal tract, it must go through the patient's liver to
undergo first-pass metabolism. During first-pass metabolism the conjugated
L-lysine is removed, and the d-amphetamine regains its therapeutic
In theory, as a prodrug, Vyvanse should carry less liability for diversion
and abuse because of the necessity to metabolize the drug before it can become
active. If someone tried to open a Vyvanse capsule and snort the powdered
ingredients, for example, or tried to dissolve the powder in water and inject
it, the result should be significantly reduced potential for the"
high" associated with amphetamine formulations.
Shire and New River said that when the prodrug was administered orally and
intravenously in two clinical human drug abuse studies, it "produced
subjective responses on a scale of 'Drug Liking Effects' (DLE) that were less
than d-amphetamine, at equivalent doses." The DLE scale is commonly used
to measure abuse potential of a medication when given to a study population of
known substance abusers.
The possibility of being able to prescribe a central nervous system
stimulant medication for patients with ADHD that carried less potential for
abuse, Shire said, should make the medication a sales blockbuster. The company
had hoped that the U.S. Drug Enforcement Administration (DEA), which regulates
controlled substances, would not list the drug as a Schedule II controlled
substance (C-II), as it does with most other stimulants. Shire was hoping for
a C-III or C-IV scheduling, in recognition of the theoretically reduced
potential for abuse.
However, pending final approval of the medication, the FDA proposed to the
DEA that lisdexamfetamine be listed as a C-II medication. In reviewing data on
the drug, the DEA concurred with the FDA's recommendation and issued a
proposed rule, listing lisdexamfetamine as a C-II controlled-substance
According to Shire and New River, clinical trials they funded of
lisdexamfetamine showed that it provided "significant efficacy compared
with placebo." In phase II and III clinical trials the medication was
associated with significant improvements in ADHD symptoms, compared with
placebo. Efficacy was demonstrated at 30 mg per day, 50 mg per day, and 70 mg
per day. In studies using a simulated school day in a classroom environment,
significant benefits were associated with lisdexamfetamine compared with mixed
amphetamine salts (Adderall XR). Significantly improved behavior as well as
significantly improved academic performance were demonstrated in those taking
lisdexamfetamine compared with study participants taking placebo.
As a stimulant medication, lisdexamfetamine will carry the same prominent
label warnings regarding increased potential for cardiovascular risks and
worsening or emergence of psychiatric symptoms, such as delusions or
hallucinations, aggression, or agitation.
The most common side effects seen in clinical trials with children taking
lisdexamfetamine were decreased appetite, difficulty falling asleep,
stomachache, and irritability.
More information regarding Vyvanse, including full prescribing
information, is posted at<www.shireadhdtreatments.com/>.▪