Positive Results from Antegren® Trial Published
Last year’s Winter 2002 issue of The Motivator
included the encouraging results of a six-month study
investigating the effects of the monoclonal antibody
natalizumab (Antegren) in 213 individuals with relapsing-remitting
and secondary-progressive MS. These results were
initially presented at the annual meeting of the
European Congress on Treatment and Research in Multiple
Sclerosis, held in September 2001.
An important step in affirming the results of any
trial is to be published in a “peer-reviewed” publication.
Antegren has recently been in the news because the
results of this study were published in the January
2, 2003 issue of The New England Journal of Medicine
(David H. Miller, et al, A Controlled Trial of Natalizumab
for Relapsing Multiple Sclerosis, vol. 348: 15-23).
As reported in The Motivator, the trial was conducted
at 26 centers in the United States, Canada, and the
United Kingdom. The 213 participants were divided
into three treatment groups: three milligrams of
Antegren per kilogram of body weight, six mg per
kg, or placebo. Doses were given via intravenous
infusion once every four weeks for a six-month period.
The study was double-blinded, so neither the participants
nor the medical staff conducting the trial knew who
was receiving the active drug and who was receiving
a placebo.
The primary outcome measure was the number of new
gadolinium-enhancing lesions (as seen on magnetic
resonance imaging, or MRI) appearing during the six-month
treatment period, indicating new disease activity.
The treatment period was considered to start one
month after starting the drug and continuing until
one month after the final dose. Other MRI outcomes
were also evaluated. In addition to MRI results,
clinical outcomes, i.e., number of relapses, self-reported
well-being scores, and changes in disability scores
as measured on the EDSS were also noted.
MRI results showed that the placebo group had a
mean average of 9.6 new gadolinium-enhancing lesions
per participant during the six-month period. Those
in the lower-dose treatment group had a mean average
of only 0.7, and those in the higher-dose group had
a mean average of only 1.1 (the differences in these
two latter scores is not significant). This represents
about a 90 percent reduction in the formation of
lesions when comparing the placebo group to the treated
groups. Significant reductions were also seen in
the secondary MRI outcomes (such as the number of
persistent enhancing lesions, new active lesions,
total volume of enhancing lesions, and the percentage
of scans showing disease activity).
Looking at clinical outcomes, a significant difference
in relapse rate was observed between the placebo
and treated groups. Of the 71 individuals in the
placebo group, 36 relapses were reported in 27 of
the patients (representing 38 percent). In the lower-dose
treatment group, 18 relapses were reported in 13
of the 68 participants. In the higher-dose treatment
group, 15 relapses were reported in 14 of the 75
participants. The latter two represent 19 percent
each – showing that approximately half the number
of individuals experienced relapses in the treated
groups as compared to those in the placebo group.
Self-reported well-being scores were improved in
the treated group, but slightly worse in those in
the placebo group. No significant changes were seen
in disability scores during the relatively short,
six-month study period.
Antegren works by interfering with the movement
of potentially dangerous immune system cells (activated
lymphocytes and monocytes) from the bloodstream across
the blood-brain barrier (BBB), into the brain and
spinal cord. Passing through the BBB is a necessary
step for the cells to attack the myelin and cause
damage to the nerves of the central nervous system
(CNS). To cross the BBB, immune system cells must
first adhere to the wall of the blood vessels. Glycoprotein
alpha 4 integrin is expressed on the surface of these
damaging cells and plays a critical role in the cells’ ability
to adhere to the blood vessel walls and then migrate
into the CNS. Antegren is an alpha 4 integrin antagonist,
thus interfering with the alpha 4 integrin’s
ability to move immune system cells into the CNS.
The drug was originally developed by the Elan Corporation.
Biogen Incorporated (makers of Avonex®) has joined
the Elan Corporation to test and ultimately seek
approval for Antegren. Larger, longer-term studies
are presently underway, with the hopes that approval
for the drug may be sought in the United States and
Europe by the end of 2003. According to The Associated
Press, Elan’s president of research and development
stated that the drug could be available as early
as the end of 2004.
Read all the
Latest News...
|
