25 Jan 2002
Multiple sclerosis is a chronic and
unpredictable disorder, with debilitating physical and mental symptoms.
However, there are few approved treatments - and most of the ones that
do exist are largely confined to speeding recovery from acute attacks of
the disorder or to managing symptoms. Will new pipeline MS drugs steal
the market leaders' hold?
Competition between the major multiple
sclerosis (MS) players is fierce, as the market is not yet mature, and
the effects of what drugs there are overlap. Manufacturers have therefore
strived to exploit any advantage of their drug over rival compounds to
the full.
"Efforts to extend product lifecycles
include obtaining new indications for subtypes of MS and producing novel
formulations," says Datamonitor healthcare analyst Anna Strudwick. "There
have also been recent regulatory changes affecting the market, adding up
to an upcoming therapeutic area."
The MS market is currently dominated
by MS-specific treatments: Betaseron, Avonex, Rebif and Copaxone. But none
of these treatments actually offer a cure for the disease, despite these
opportunities for manufacturers wishing to enter the market the R&D
pipeline is still inactive.
Biogen's Avonex is currently the
MS market leader, with sales of $761 million in 2000. However, two recent
head-to-head clinical trials have found that Avonex is less effective than
either Serono's Rebif or Berlex (part of Schering-Plough) and Chiron's
Betaseron. Ms Strudwick believes these results will "limit Avonex's continued
ascendancy."
Checking out the EVIDENCE
In the EVIDENCE study, which compared
Avonex with Rebif and Betaseron, Rebif was found to be significantly more
effective than Avonex in terms of all clinical outcome measures. Patients
on Rebif had a lower rate of MS exacerbations, and a higher proportion
remained exacerbation-free than patients on Avonex.
At the same time, Rebif reduced the
number of active lesions by a third compered with Avonex, and the proportion
of patients with no active lesions at the end of the study was significantly
greater in the Rebif group.
Injection site reactions were more
common in the Rebif group, largely because the drug needs to be administered
more frequently. However, there was no difference regarding serious adverse
events, which were infrequent in both groups.
Unsurprisingly, Biogen has put up
considerable opposition to the EVIDENCE study. The company claims that
the study was misleading and lacked scientific vigor. Biogen has contended
that the results were statistically manipulated to present Rebif in a more
positive light, and that the trial was too short in duration.
Biogen fights to stay ahead
Biogen's challenge has been partly
successful: in June 2001, a Swiss court injunction was issued forbidding
Serono to continue claiming that those treated with Rebif in the study
had a 90% greater chance of remaining relapse-free, as the statistical
basis of this claim was misleading. However, the fact that the presentation
went ahead at the World Congress of Neurology anyway suggests that the
study may still have some influence.
In the US, where Rebif is unavailable
due to Avonex's orphan drug exclusivity, Serono has submitted the EVIDENCE
results to the FDA. According to Ms Strudwick, "this evidence is likely
to be successful in allowing Rebif's launch in the US in 2002 before Avonex's
orphan drug status runs out in 2003. Rebif's case will be boosted by its
position as the leading RRMS treatment outside the US."
However, EVIDENCE isn't all bad news
for Biogen. The trial showed that both drugs can delay the progression
of the disease, and as a result Ms Strudwick expects that "the EVIDENCE
findings will have a positive impact of 5-10% on sales of these drugs as
they will effectively extend the MS treatment window."
Meanwhile, back at the lab...
In the long term, the biggest threat
to Avonex will come from drugs further back in the pipeline. Copaxone is
leading the competition in terms of new drug formulations. However, disappointing
results from a Phase III trial of oral Copaxone suggest that it will not
be launched until 2007.
Meanwhile in the UK, the cost-effectiveness
and consequent revenue potential of the MS specific treatments has been
put in doubt by proposed NICE guidelines. However, Ms Strudwick believes
"the initiation of extensive UK clinical trials will counteract this factor
to some extent, resulting in only a modest negative impact of around 0.1%
on the global market."
"The predominant factor influencing
the MS market will be the continued uptake of MS specific drugs in interferon
naive patients. This immaturity will drive the market's growth through
to 2008," she adds.
However, the launch of several novel
drug classes from 2006 onwards is unlikely to have an impact on the overall
market size, as the main uptake of these drugs will be as a replacement
for the currently marketed products.
Old favorites fare well
In the meantime, Ms Strudwick believes
that "the marketed drugs will dominate the MS market. The aggressive measures
pursued by all of the manufacturers of these drugs to extend their lifecycles,
such as efforts to gain new indications, will ensure that sales continue
to be strong."
Only the recently launched Novantrone
is expected to have any impact on the market standards' sales figures,
but even that is unlikely to have any substantial effect, as Novantrone
is indicated for secondary progressive MS whereas the predominant usage
of the marketed drugs is currently for relapse/remitting MS. As well as
this, Novantrone is hindered by its side effect profile, which is considerably
worse than the marketed drugs.
For now at least
However, the launches of several
new drug classes in 2006 and 2007 will make a significant impact on the
currently marketed products, resulting in a reduction in their sales.
According to Ms Strudwick "these
drugs will affect interferons sales more than Copaxone, as the expected
launch of the oral formulation of Copaxone in 2007 will counteract the
negative impact to a certain extent. Until then Avonex looks set to rule
the roost."