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The "COX-2" Inhibitors
21 May 1999, the US Food and
Drug Administration (FDA) approved Merck & Co’s Vioxx
(rofecoxib) for the relief of the signs and symptoms
of osteoarthritis, management of acute pain in adults, and
the treatment of menstrual pain, or primary dysmenorrhea.
It became the second cyclo-oxygenase 2, or COX-2, inhibitor
on the market, following the Monsanto subsidiary Searle’s
Celebrex (celecoxib), launched in the US in January
1999, and being co-marketed by Pfizer.
The COX-2 inhibitors are the
biggest single innovation in the treatment of arthritis
symptoms since the introduction of non-steroidal anti-inflammatory
drugs (NSAIDs), and indeed early sales of Celebrex and Vioxx
have surpassed those of even Pfizer’s impotence blockbuster
drug Viagra (sildenafil). IMS HEALTH reported (June
8 1999) that in the first 10 days of prescription activity,
4,797 prescriptions for Vioxx were dispensed in the
US. This compares to 3,231 prescriptions for Celebrex over
the same period. At 15 weeks post launch, total Celebrex
prescriptions dispensed in the US had reached 3.2 million.
These drugs have taken over
20% of the total arthritis market, possibly due to their
competitive pricing, which is on a par with popular NSAIDs.
The FDA did not grant Celebrex an acute pain indication,
only the relief of arthritic pain. Merck & Co said one
of the reasons it was a few months behind Searle was the
rigorous pain models it had taken time to do; unlike Celebrex,
however, it does not have a rheumatoid arthritis indication
initially. Vioxx is seen as crucial in the performance
of Merck & Co over the next few years - the company
planned to add 700 sales representatives to its team of
4,000 in preparation for the launch.
IMS HEALTH’s therapy class
forecasting system, Pharmacast
&Beyond, forecasts that overall sales of
M1A non-steroidal anti-rheumatics in the USA will be boosted
by 20% as a result of the launch of the COX-2 inhibitors,
with total revenues exceeding $2.5 billion by 2008.
The COX-2 inhibitors, also
known as ‘super aspirins’, are designed to work as effectively
as traditional NSAIDs, but without side effects such as
ulcers and gastrointestinal bleeding. The enzyme COX-2 is
responsible for converting arachidonic acid to ‘inducible’
prostaglandins, which produce inflammation and exacerbate
tissue injury at the site of injury. The new inhibitors
are more selective for COX-2 and hence do not interfere
with the production of ‘good’ constitutive prostaglandins.
The non-selective inhibition of both COX-1 and COX-2 in
other NSAIDs is responsible for the toxicities and side
effects.
Despite the increased
safety of the new drugs, both Searle and Merck & Co
have to include the standard gastrointestinal warnings for
NSAIDs on their products; the FDA has, however, said these
warnings could be omitted in the future if further studies
provide more definitive GI safety data. However, neither
drug is completely without side effects.
For more information about
Monsanto, Merck & Co and Pfizer, see the relevant
Pharmaceutical
Company Profiles. Further scientific information on
the COX-2 inhibitors, including the follow-up compounds
to Celebrex and Vioxx and other possible indications,
can be found on R&Dfocus,
whilst Drug
Launches will monitor the rollout of the drugs internationally.
Details of the molecules, intermediates and possible synthetic
routes of the COX-2 inhibitors are included on Pioneer.
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