| Celltech,
one of Europe's largest biotechnology companies, with
its potential treatment for rheumatoid arthritis (RA),
the humanized monoclonal antibody (MAb) fragment CDP
870, may well emerge as the mouse that confronts the
elephant.
CDP 870, targeted to tumour necrosis factor alpha,
"could be a serious competitor to Immunex's Enbrel
(etanercept)", quoted brokers Goldman Sachs. Morgan
Stanley Dean Witter in October 2000 said, "CDP 870
is a product that could transform Celltech - it is
the real sleeper in the Celltech portfolio."
As
recently as 1999, the RA market exploded out of its
reveries with the introduction of the COX-2
inhibitors (Pharmacia's/Pfizer's Celebrex and
Merck & Co's Vioxx), the biggest single innovation
in its treatment history since the introduction of
the non-steroidal anti-inflammatory drugs (NSAIDs).
With
the launch of Celebrex alone, Searle (subsequently
taken over by Pharmacia) expanded the arthritis pain
market by 20%. CDP 870, which Celltech believes could
be launched in 2004, may transform this market yet
again.
Such a concept is far from being a fantasy - in January
2001, Celltech announced that it was in talks with
four leading pharmaceutical companies interested in
a pivotal licensing deal for RA - this could be struck
before the end of March 2001. Amongst the companies
touted are Pfizer, Pharmacia and GlaxoSmithKline
- these companies have independently estimated peak
sales for CDP 870 above $1 billion, more than double
the amount forecast by most analysts.
Source:
Monthly
MIDAS
*Retail pharmacy markets in the US, Canada, Germany,
Italy, France, Spain, UK, Brazil, Mexico, Argentina,
New Zealand and Japan - approximately 80% of global
pharmaceutical sales
Anti-TNFs versus the COX-2s
The two main indications to date for the anti-TNFs
are Crohn's disease and RA. Regarding what might be
the main indication for CDP 870, Richard Bungay, Celltech's
Director of Corporate Communications & Strategic Planning
told IMS HEALTH, during an interview in December 2000,
that he believed that all the anti-TNFs will want
to go for the same claim, which is treating the signs
and symptoms of RA and reversing structural damage,
then working down into the less severe patients.
IMS HEALTH asked Bungay how CDP 870 was being positioned
vis-à-vis the COX-2s. Bungay replied that CDP 870
is targeted to a different end of the market:
"The COX-2s are being positioned for symptomatic relief,
mainly at the mild-to-moderate end of the RA spectrum.
Enbrel is the best benchmark for where CDP 870 will
be positioned - predominantly at the more severe end
of the market, not only for treating the signs and
symptoms, but also for stopping and, potentially,
reversing joint damage."
Bungay indicated that Celltech's limited experience
to date with CDP 870 suggests a similar clinical profile
to other anti-TNFs. However, as to actually reversing
damage already done, "this has not been specifically
investigated with CDP 870 to date, because only a
small degree of cartilage destruction can be enormous
in terms of function lost and one needs to measure
this destruction over an extended period. I think
however there is growing confidence amongst rheumatologists
that anti-TNF agents will get this claim eventually."
Safety and competition for CDP 870
One of the big questions is whether anti-TNFs are
safe long-term. Remicade (infliximab), an anti-TNF
used in Crohn's disease, is used with methotrexate,
but this is because Remicade gives rise to an immune
response and methotrexate suppresses the resulting
antibodies. Bungay explained that because CDP 870
is humanized, Celltech does not envisage any immunogenicity
problems, "Celltech will be positioning CDP 870 as
monotherapy."
Regarding existing competition to CDP 870, Bungay
said that the main two competitors already on the
market are Johnson & Johnson/Centocor's Remicade and
Enbrel. In the future, competition will come from
Knoll (in the process of being acquired by Abbott),
in the guise of its MAb against TNF-alpha, D2E7, currently
in Phase III trials.
Concerning how much the actual market might be worth,
Bungay said he had seen estimates ranging from $2
to $4 billion for the anti-TNFs, based on fairly limited
penetration at the mild-to-moderate end of the RA
spectrum.
| Sales
of the top six NSAIDs (M1A)
(12 months ending November 2000*)
|
| Product
|
Compound
|
Rank
|
Corporation
|
Sales
(US$ millions) |
| Celebrex
|
celecoxib
|
1
|
Pharmacia
|
1,749.1 |
| Vioxx
|
rofecoxib
|
2
|
Merck
& Co |
1,299.9 |
| Voltaren
|
diclofenac
|
3
|
Novartis
|
552.6 |
| Relifex
|
nabumetone
|
4
|
SmithKline
Beecham |
270.1 |
| Loxonin
|
loxoprofen
|
5
|
Sankyo
|
242.5 |
| Arthrotec
|
diclofenac/
misoprostol |
6
|
Pharmacia
|
217.0 |
Source:
Monthly MIDAS
*Retail pharmacy markets in the US, Canada, Germany,
Italy, France, Spain, UK, Brazil, Mexico, Argentina,
New Zealand and Japan - approximately 80% of global
pharmaceutical sales
Apart from RA and Crohn's, anti-TNFs are being looked
at in congestive heart failure, psoriasis and other
arthropathies, and especially psoriatic arthropathy.
Celltech envisages a number of other potential indications
for CDP 870.
Bungay stressed that share of voice, in both the RA
and Crohn's markets, will be very important. Celltech
is in discussions with potential partners in RA (see
above) but sees itself doing the majority of the promotion
in Crohn's, since this is mainly a disease treated
by hospital specialists, a much smaller group to target
than GPs and family practitioners.
Future products with potential
With respect to other Celltech programmes, Bungay
said that he anticipated quite a few potential product
launches in the period to 2005. In terms of in-house
products, Celltech has another humanized anti-TNF
antibody, Humicade, in Phase III trials for Crohn's
disease, which could be launched in 2002 or 2003.
The company also has CDP 860, in Phase II trials for
restenosis.
Scientific rationale is that this anti-PDGF beta-receptor
antibody (the PDGF beta-receptors are antagonized
during angioplasty or stenting, leading to cell proliferation
and reblocking of the artery) blocks the PDGF beta-receptor,
and so prevents reocclusion of the arteries.
Angioplasty, as well as treating arterial blockade,
is now being used in treating venous blockade of the
major veins and in peripheral arterial disease. CDP
860 could potentially be launched by 2005.
Celltech, moreover, has a number of partnered products
which the partners could launch before 2005, and from
which the company would receive royalties. For example,
with Bristol-Myers Squibb it has an MMPI (matrix metalloproteinase
inhibitor), BMS 275291, currently in Phase II trials
for the treatment of cancer - Celltech will receive
a royalty on sales but has no involvement in the clinical
trials.
With Schering-Plough, Celltech has SCH 55700 for the
treatment of seasonal allergic reactions in asthmatics,
currently in Phase II trials. SCH 55700 will compete
with Genentech/Novartis' omalizumab (MAb IgE or MAb
E25), and is being aimed at moderate-to-severe asthma.
IMS HEALTH asked Bungay whether he saw a 'gap' in
Celltech's revenues between 2002 and 2005 (i.e. before
the company launches pipeline products with projected
good revenues), due to the shortfall left by its treatment
for hyperactive children, methylphenidate.
Bungay replied that Celltech plans to launch its modified-release
methylphenidate, subject to regulatory approval, during
2001. It also has ongoing royalties from its 'Boss'
patent, Chirocaine (for pain relief), and to a greater
extent, Mylotarg,
launched by American Home Products in the USA in 2000
for the treatment of acute myeloid leukemia:
"These royalties will increase substantially as the
underlying products realise their full potential,"
concluded Bungay. |
