 | placebo
(which was the primary outcome of the trial). However, Betaseron did
reduce annual relapse rates in study subjects (this was a secondary
outcome of the study). The treatment also showed reduced
accumulation of brain lesions detected by MRI.
|
| These
results differ from a European study of interferon beta-1b
(Betaferon), conducted by Schering AG (Berlin), Berlex Laboratories'
parent company, where the drug produced statistically significant
slowing of progression of disability as well as reduction of relapse
rate and accumulation of new MRI-detected brain lesions.
|
| While
both studies focused on SP MS, there were some key differences in
the study populations, which may have resulted in these very
different outcomes. This question is undergoing analysis.
|
| Berlex
Laboratories has submitted its data and results from this trial, as
well as from the successful European study to the U.S. Food and Drug
Administration for consideration, with the hope that approval for
Betaseron in the U.S. will be expanded to include
secondary-progressive MS.
|
Details:
Berlex Laboratories (Richmond, CA) recently announced mixed results from
its North American multicenter clinical trial of interferon beta-1b
(Betaseron®) for secondary-progressive multiple sclerosis (SP MS). In
this study, injection under the skin of Betaseron three times a week for
over two years failed to slow progression of disability compared with
inactive placebo. This was the primary outcome of the study established by
investigators before the study began. However, significant benefit with
treatment was seen in several secondary outcomes, including reduced
relapse rate and reduced steroid use for relapses. There was also reduced
accumulation of new brain lesions and of persistent lesions detected by
MRI.
These
data differ from those collected in a similar European study of Betaferon
(which is the same drug), which terminated early in 1998 because of
overwhelming benefit. Differences between the two studies that may have
contributed to these very different results are being explored. Initial
analysis indicates that, when compared with the European study group, the
North American study group tended to be older, with a longer history of
MS, and with fewer relapses in the two years prior to the study and fewer
new "enhancing" lesions detected by MRI. This suggests that
Betaseron may be most effective in slowing secondary progressive MS for
individuals relatively early in their progressive phase: those who are
still experiencing relapses and who have active inflammation in brain
lesions, seen as new gadolinium enhancing MRI-detected lesions.
Background: People with SP MS first experience a relapsing-remitting course, and
later develop progressive worsening, with or without occasional relapses.
About 50% of those who start with a relapsing-remitting course eventually
develop SP MS. Betaseron was approved for treating relapsing-remitting MS
in 1993. Studies of this medication in SP disease were undertaken to
determine the safety and efficacy of the agent on this different form of
the disease.
The
North American study took place at 35 clinical centres in the U.S. and
Canada and involved 939 individuals with SP MS. Participants in the study
self-injected Betaseron under the skin every other day. One-third of study
subjects used the "standard" dose of Betaseron, currently
approved for relapsing-remitting disease; one-third used a variable dose,
based on body size; and one-third injected inactive placebo. The study was
intended to run for three full years.
In
early September 1999 Berlex Laboratories terminated the study, slightly in
advance of the originally planned end date of April 2000. This decision
was based on a recommendation from an independent monitoring committee
that undertook a pre-planned interim analysis of results in late August
1999. This analysis showed that, some seven months in advance of the
planned end date, adequate data had been gathered to evaluate the results.
Upon the committee's recommendation for termination, final study exams
were moved forward for all individuals remaining under treatment and data
on safety and efficacy were evaluated.
What
do these results mean? The
mixed results from this study are disappointing, since Betaseron failed to
achieve its primary goal of slowing progression of disability. Other
clinical trials of interferon’s in SP MS have also provided mixed
results. While the study of interferon beta-1b (Betaferon) in Europe
showed positive benefit in slowing progression, a study of interferon
beta-1a (Rebif) failed to slow progression of disability, although it did
show benefit on relapses and MRI similar to Betaseron's results in this
North American study. The reasons why these studies have produced
different results are unclear, and clarification of these reasons will
help to determine the future of interferon beta as a treatment for SP MS.
The detected differences in patient populations between the North American
(Betaseron) and European (Betaferon) studies may point to important
differences in stages of disease progression and the impact of interferons
on progression. The U.S. Food and Drug Administration has been asked to
review all of the data relating to use of interferon beta-1b (both
Betaferon and Betaseron) for SP MS and to make a determination about
approval for marketing based on its overall efficacy and safety in this
form of disease.
Individuals
who are interested in the use of Betaseron for secondary-progressive MS
should consult their personal physicians or call Berlex at (1-888)
237-5394 (1-888-Berlex4) for further information.
