| In
the 12 months to November 2000, the psychostimulant
(N6B) market was worth over $625 million, up 7%
from the previous year according to IMS HEALTH's Monthly
MIDAS service, which tracks retail pharmacy sales
in the 13 major global markets.
This class is dominated by treatments for attention-deficit
hyperactivity disorder, or ADHD, and the related
condition ADD - attention-deficit disorder (trouble
with focus and attention, but no hyperactivity). The
leading drug is Shire's Adderall, a combination
of amphetamine and dexamphetamine. This is followed
by Novartis' Ritalin (methylphenidate). There
are also many generic versions of methylphenidate
(MP) on the market.
Source:
Monthly MIDAS
*Retail pharmacy sales in the USA, UK, Canada, France,
Germany, Italy, Spain, Argentina, Brazil, Mexico,
Australia, New Zealand and Japan
In
the 12 months to November 2000, Shire's Adderall had
33.3% of the psychostimulant market - and saw 61%
growth over the previous 12 months. Ritalin's
sales dropped 12%, but Novartis' generic methylphenidate
witnessed a 75% increase in sales, and it is now lying
in sixth place with 5.8% of the N6B market.
Methylphenidate products from Bristol-Myers Squibb,
Watson, and Celltech all saw significant (-37 to -66%)
falls in their sales from the previous year, as did
Abbott's Cylert (pemoline).
New products grow market - challenges for Adderall
One reason for these decreasing sales is the introduction
of newer products. Only launched in August 2000, ALZA's
Concerta is the first once-daily methylphenidate
product, and is co-marketed by Johnson & Johnson's
McNeil Consumer Healthcare division. It is already
ranked fifth, with 6.2% of the psychostimulant market
in the Monthly MIDAS universe.
Celltech has launched an extended-release methylphenidate
product, Metadate ER, which is in 12th place.
Mallinckrodt's methylphenidate Methylin performed
very well, seeing 103% growth to reach eighth place.
In December 2000, the FDA approved a 54mg tablet of
Concerta, so it is now available in three doses (also
18mg and 36mg). The product's main advantage is that
children can avoid taking their medication whilst
at school, or before participating in after-school
activities. Rival manufacturer Shire, perhaps putting
a brave face on the situation, believes Concerta may
grow the ADHD market; nevertheless, it has developed
its own once-daily product, Adderall XR, currently
awaiting FDA approval.
Shire's lead product (it accounted for 41% of Shire's
revenue in 2000) is now also vulnerable to generic
competition. Although Adderall consists of four
off-patent amphetamines, Shire maintained that generic
manufacturers did not possess certain necessary technical
manufacturing information. But, in November 2000,
Cambrex announced that it had the capability to make
generic Adderall - leading to a 9% drop in Shire's
share price.
Ritalin use sparks controversy
Ritalin's performance has been hampered by controversy,
specifically charges of its over-use. The US group
Parents Against Ritalin claims that in some classes,
25% of children are on Ritalin, and the number
of very young children on the drug grew sharply in
the 1990s.
Yet the US National Institute of Mental Health believes
only 3-5% of American children suffer from ADHD. One
factor contributing to the rising numbers may be a
federal government programme, which provides financial
assistance to low-income families with an ADHD child.
In 2000, Ritalin manufacturer Novartis, the American
Psychiatric Association, and an ADHD support group
were named as defendants in a number of class-action
lawsuits. These claim that the three parties colluded
to expand the diagnosis of ADHD, thus boosting Ritalin
sales.
Some believe that ADHD has just been under-diagnosed
and untreated in the past, but others are alarmed
at the number of children being given powerful stimulant
drugs. The lack of an objective, biological diagnostic
test also complicates the issue.
The controversy spread to the UK in the autumn of
2000, when the National Institute of Clinical Excellence
(NICE) approved the use of methylphenidate in ADHD.
NICE said the drug should be used as part of a comprehensive
treatment programme in severely affected children.
Although the decision did attract some criticism,
a UK ADHD family support group welcomed the move,
and Professor Peter Hill, a consultant in child and
adolescent psychiatry from Great Ormond Street Hospital
noted, "I don't think there is any doubt at all that
in medical terms methylphenidate is an effective way
of squashing the symptoms." He also pointed out that
affected children often spiral into low self-esteem
due to the constant criticism and reprimands, which
treatment could prevent.
Mechanism of action research
Although methylphenidate has been used in ADHD for
many years, its mechanism of action has never been
clear. The January 2001 issue of the Journal of Neuroscience
included a paper which showed, via the use of positron
emission tomography, that Ritalin increases levels
of the neurotransmitter dopamine in healthy male
subjects.
By amplifying the release of dopamine, methylphenidate
may enhance task-specific signalling, thus improving
attention and decreasing distractibility, according
to the scientists. Their work may also explain why
Ritalin, when used properly, is not addictive (unlike
many drugs that affect the release of dopamine): because
the oral dose takes about an hour to affect the brain,
it does not create an addictive "high".
New products on the horizon
In October 2000, Shire filed SLI 381 (Adderall
XR) for approval with the FDA. This is a once-daily
version of current ADHD market leader Adderall. The
product is obviously vital for Shire, given the success
of once-daily Concerta from rivals ALZA and J&J, and
will be featured at the APA meeting in May 2001.
Behind SLI 381, Shire has two further ADHD drugs in
development. SPD 420 is an ampakine licensed
from Cortex, and was in Phase I trials at the beginning
of 2001. This is described as a novel treatment, and
will be non-scheduled (i.e. not regulated by the US
Drug Enforcement Agency). SPD 503 is another
non-scheduled compound, also in Phase I trials, and
aimed at "certain subsets" of symptoms in ADHD patients.
Both Celltech
and Novartis have follow-ups to their current drugs
pending approval with the FDA. Celltech's Medeva subsidiary
has a once-daily modified-release methylphenidate
product, Metadate MR, which uses Eurand's Diffucaps
technology, while Novartis has licensed Attenade
(d-methylphenidate), described as "chirally pure"
Ritalin, from Celgene. Noven is developing a once-daily
transdermal methylphenidate patch, MethyPatch,
in Phase III trials.
A new player in the ADHD market is Eli Lilly, with
tomoxetine, in Phase III trials. Tomoxetine
could be filed for approval before the end of 2001,
and is already attracting attention. It may benefit
from not being a stimulant, thus causing fewer side-effects
such as insomnia and lethargy, and making it more
acceptable to parents and other concerned groups (although
it can cause appetite suppression).
Whereas most current ADHD treatments affect dopamine
uptake, tomoxetine blocks norepinephrine reuptake.
It would be taken twice a day. GlaxoSmithKline
is also working on a non-stimulant drug for ADHD (GW
320659). Gliatech has developed another type of
compound: Perceptin, a histamine H3 antagonist,
is now in Phase II trials in adult ADHD patients. |
