| In
February 2001, two new antihistamines were launched:
Neoclarityn from Schering-Plough in the UK,
and Xusal from UCB in Germany. The two drugs
were developed by US specialty company Sepracor, and
joined a third Sepracor-originated antihistamine,
Allegra (marketed by Aventis), on the world
market.
Sepracor describes its products as Improved Chemical
Entities, or ICEs. These are single isomers or
active metabolites of marketed drugs, which have the
potential to become products different from the parent
compound in terms of clinical efficacy and/or side
effect profile.
Many drugs are administered in a racemic form, i.e.
the drug is an equal mix of two forms that are mirror
images of each other, or chiral isomers (termed R
and S). Often only one isomer is responsible for the
drug's efficacy and the other may be responsible for
undesirable side effects. Sepracor has a pipeline
of several such refined products. Currently, the company
markets only one drug itself, Xopenex (levoalbuterol),
for asthma. Allegra was the first product launched
from its research.
The systemic antihistamine (class R6A) market was
the world's 11th largest in 2000, worth $5.5 billion,
and with growth of 18% over 1999 in US dollar terms,
according to IMS HEALTH's World
Review.
Systemic
antihistamine (R6A) market share
(12 months to December 2000*)
 |
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 world's 13 leading retail markets, tracked
by IMS HEALTH's Monthly
MIDAS system, Claritin (loratadine) has
a 39.1% market share, followed by Zyrtec (cetirizine)
with 21.0%. Pfizer markets Zyrtec in North America.
Ranked third is Allegra/Telfast (fexofenadine), with
a 15.8% market share in the Monthly MIDAS universe.
Patent
expiries loom
Claritin and Zyrtec came to prominence in the late
1990s, when two older antihistamines were withdrawn.
Hoechst Marion Roussel (now Aventis) withdrew Seldane
(terfenadine) from the US market in 1998, after it
had introduced the metabolite Allegra. Hismanal
(astemizole) was withdrawn worldwide by Johnson &
Johnson in 1999, as, like Seldane, it was linked to
the development of cardiovascular side effects.
The antihistamine market is now entering another state
of flux, as Claritin faces patent expiry. The European
and Japanese patents will begin to expire in June
2001, according to Patents
International, with US patent expiry following
in June 2002. Zyrtec's European patents also begin
to expire in 2002.
Schering-Plough and UCB have endeavoured to extend
the lifecycle of their products through decongestant
combinations, new formulations, paediatric trials
etc. Schering-Plough has even lobbied US Congress
for a change in the Waxman-Hatch Act, a 1984 law that
granted patent extensions to compensate for delays
at the FDA.
But both companies also began collaborations for second-generation
versions of their antihistamines with Sepracor. The
company has a unique strategy within the pharmaceutical
industry, in that it concentrates on the development
of single isomers and active metabolites of marketed
drugs. These have the potential to become products
that are different from the parent compound in terms
of clinical efficacy and/or side effect profile.
| Sepracor
antihistamines
| Brand
name |
Compound
|
Parent
product |
Licensed
to |
Status |
| Allegra/Telfast
|
fexofenadine
|
Seldane
(terfenadine) |
Aventis
(Worldwide) |
Worldwide:
marketed |
| Neoclarityn
/ Aerius / Clarinex |
desloratadine
|
Claritin
(loratadine) |
Schering-Plough
(Worldwide) |
UK/Germany:
marketed
EU: approved
US: pending |
| Xusal/Xyzal
|
levocetirizine
|
Zyrtec
(cetirizine) |
UCB
(Europe) |
Germany:
marketed
EU: pending
US: pending |
| Soltara
|
norastemizole
|
Hismanal
(astemizole) |
--
|
|
|
Source:
Pharmaceutical Company Profiles
In 1998, before the withdrawal of Hismanal, J&J also
signed a licensing agreement with Sepracor for a follow-up
compound, norastemizole. In 1999, however, J&J declined
to exercise its co-promotion option. Sepracor elected
to continue development of the product independently,
and it was filed for approval in allergic rhinitis
in March 2001, as Soltara. J&J provided Sepracor
with some astemizole reference data for inclusion
in the norastemizole NDA, and will be entitled to
royalties in return.
Norastemizole does not appear to cause the cardiovascular
side effects of Hismanal, or sedation. Apart from
capsules, Sepracor is also developing a combination
product with pseudoephedrine, a syrup, and a rapidly-dissolving
tablet formulation. Sepracor will be boosting its
sales force in preparation for Soltara's launch, and
is planning a $200 million direct-to-consumer advertising
campaign (Claritin has the highest DTC ad spend in
the industry). It may even develop Soltara as an over-the-counter
product. Sepracor has already conducted a head-to-head
trial of Soltara against Claritin, which apparently
demonstrated Soltara's faster onset of action.
Claritin successor hits delays in US
Sepracor is perhaps wise to develop an independent
stance, as at present it is vulnerable to fallout
from problems with its licensees. This was seen in
February 2001 when the approval of desloratadine in
the US, where it will be marketed as Clarinex,
hit a delay. Sepracor's share price fell 10.5% when
the FDA found Good Manufacturing Practice (GMP) compliance
problems at two Schering-Plough manufacturing facilities.
The main issue for Sepracor is that the GMP deficiencies
must be resolved before the FDA approves Clarinex.
The agency finally issued an 'approvable' letter for
the product in January 2001 (the NDA was filed in
October 1999), after which Schering-Plough submitted
revised product labeling as requested.
Despite these problems, most believe Sepracor's strategy
will prove successful. The advantage of the ICE programme
is that the safety and efficacy of the parent drugs
are well understood, therefore development may be
accomplished faster and at a lower cost than for new
chemical entities (NCEs). Sepracor calculates a development
time from IND to NDA of 2-3 years for an ICE pharmaceutical,
compared to 5-7 years for an NCE.
From its early days, Sepracor has been filing patents
to cover many single isomers and active metabolites,
and it now has over 30 granted US patents for ICEs.
In possession of these patents, Sepracor is in a position
to seek licensing agreements with the marketer of
the parent drug. This can further accelerate development,
as such a licensee can provide data necessary for
filing marketing approvals. Moreover, companies are
often keen to partner with Sepracor as the ICE can
provide an opportunity to extend the parent product's
franchise, in terms of patent life or new indications.
As the only other significant allergy drug nearing
approval is the anti-IgE monoclonal antibody Xolair
(omalizumab), from Genentech, Novartis and Tanox,
Sepracor seems to have won itself a significant niche
in a lucrative market.
Find out more about Sepracor in IMS HEALTH's new Pharmaceutical
Company Profile on the company, published in March
2001. This provides a detailed breakdown of Sepracor's
strategy, products, R&D and events. |
