| With
the promise of fewer gastrointestinal side-effects,
the COX-2 inhibitors have made a significant
impact on the non-steroidal antirheumatics market.
Celebrex and Vioxx account for almost 40% of sales
in the USA; however, in the UK uptake has been much
slower.
Pharmacia Corporation's attempt to have the labeling
of Celebrex relaxed to reflect reduced GI side-effects
does not seem to have succeeded - but if Merck & Co
can convince the FDA to relax the labeling on Vioxx
it could have a significant impact on the overall
market.
Current COX-2s
The
launch of the COX-2 inhibitors had a tremendous
impact on sales in the antirheumatic market. With
the promise of fewer gastrointestinal (GI) side-effects
they were expected to have a significant effect on
the way physicians prescribed for the treatment of
osteo- and rheumatoid arthritis. There are currently
two COX-2 inhibitors available:
- Merck
& Co's Vioxx (rofecoxib)
- Pharmacia
subsidiary Searle's Celebrex (celecoxib), co-promoted
by Pfizer
The
promoted advantage of using a COX-2 inhibitor over traditional
NSAIDs (non-steroidal anti-inflammatory drugs) is the
selective blocking of only the COX-2, and not the COX-1,
enzyme - which is believed to be the cause of GI side-effects.
The patient is therefore offered a safer alternative
with efficacy comparable to NSAIDs.
Debate and research is ongoing to conclusively support
this premise, but this approach has already been highly
successful for the two products currently available.
Their success as leading products in the US antirheumatics
market has not, however, been duplicated in Europe -
where sales have proved less successful.
Slower uptake in the UK
Celebrex was launched in the USA in January 1999, followed
by Vioxx in May 1999. In just two years the COX-2 inhibitors
now account for almost 40% of the total antirheumatic
market in the USA.
US Non-Steroidal Antirheumatic Market
1998 - 2000
|
Source: MIDAS
In Europe, Vioxx entered its first market, the UK, in
June 1999. Celebrex did not enter the European market
until April 2000, when it was also first launched in
the UK. Uptake of the COX-2s has been much slower in
the UK market, although Celebrex has been more successful
than Vioxx.
UK Non-Steroidal Antirheumatic Market
1998 - 2000
|
Source:
MIDAS
Reduced GI side-effects?
At the American College of Rheumatology's 64th
Annual Scientific Meeting, held October 29 - November
2 2000, findings from the VIGOR (Vioxx Gastrointestinal
Outcomes Research) study were presented. The study
evaluated 8,076 patients and compared Vioxx 50mg once-daily
with naproxen 500mg twice-daily in patients with rheumatoid
arthritis. The findings concluded that Vioxx:
- Decreased
the risk of being hospitalized for serious GI side-effects
- Decreased
the use of drugs to prevent GI side-effects
- Decreased
the use of upper GI diagnostic procedures by 25%
- Reduced
the use of gastroprotective agents by 23% compared
to naproxen
FDA
strikes a blow
Pharmacia's Searle division presented data to the
FDA hoping to convince the agency of the reduced risk
of GI side-effects compared with traditional NSAIDs,
thereby allowing it to relax warning labels. But,
in February 2001, the FDA's Arthritis Advisory Committee
concluded that Celebrex "did not demonstrate statistical
superiority to NSAIDs" and that therefore it would
not recommend a relaxation of the labeling.
Merck & Co also presented data from the VIGOR study
on its COX-2 inhibitor, Vioxx, to the FDA panel with
similar hopes of proving a reduced risk of GI side-effects.
The committee supported the results, and recommended
to the FDA that the results of the study should be
reflected in the labeling of Vioxx. The FDA will now
take this under consideration.
If the FDA rules to allow Merck & Co to relax its
labeling regarding GI side-effects, it could be just
the edge Vioxx needs to push ahead of Celebrex. However,
FDA concerns about an increased risk of heart attack
for patients taking Vioxx may take the shine off any
favourable decision.
Pipeline products
In the near future the non-steroidal antirheumatics
market will become even more competitive with the
addition of new entrants. According to IMS HEALTH's
R&Dfocus, there are currently three COX-2 inhibitors
in Phase III trials:
- Merck
& Co's etoricoxib
- Pharmacia
and Pfizer's valdecoxib, which is pending approval
- Novartis'
COX-189
There is a large amount of R&D activity in the non-steroidal
antirheumatics market in general, including several
other COX-2 inhibitors in the pipeline.
COX-2
Inhibitors in Development
| Drug
Name |
Company
|
Latest
Phase |
| darbufelone
|
Pfizer
|
Phase
II |
| CS
502 |
Sankyo
|
Phase
I |
| LAS
34475 |
Almirall
Prodesfarma |
Phase
I |
| LAS
34555 |
Almirall
Prodesfarma |
Phase
I |
| L
745337 |
Merck
& Co |
Preclinical
|
| S
33516 |
Servier
|
Preclinical
|
| SD
8381 |
Pharmacia
Corp. |
Preclinical
|
|
Source:
R&Dfocus |
