Now
Aubagio: The road
to approval and beyond
when Aubagio (the brand name of teriflunomide,
manufactured by Genzyme, a
Sanofi company) was approved
by the U.S. Food and Drug
Administration (FDA) last
September to treat relapsing
multiple sclerosis, it became
only the second oral disease-modifying therapy approved
for this disease—and its
very development was a bit
surprising.
An unexpected finding
In the 1980s, the chemical
company Hoechst AG was
screening numerous compounds
for use in agricultural pesticides.
The company’s researchers
discovered that one of the
pesticides actually had the
ability to defend against
inflammation, which occurs in
MS. The compound eventually
was developed into the drug
leflunomide, which was
approved to treat rheumatoid
arthritis, another disease that
involves immune attacks.
In 2004, Dr. Thomas Korn
(Universität des Saarlandes,
Homburg, Germany) and his
colleagues found that leflunomide
prevented the development of
EAE (experimental autoimmune
encephalomyelitis), a disease
similar to MS, in mice bred to
be susceptible to it (Journal
of Leukocyte Biology,
2004;76: 950). A “metabolite”
of leflunomide—a molecule
produced when leflunomide
is digested—suppressed
inflammation as well, and became
known as “teriflunomide.” Sanofi
Aventis began testing it in people
with MS, and its company
Genzyme brought the therapy to
the finish line.
How does it work?
In MS, immune cells such as
“T cells” and “B cells” are key
players in the attack on the
nervous system. Teriflunomide
inhibits enzymes that help
these cells to proliferate, so it
can reduce the number of cells
entering and attacking the brain
and spinal cord.
The clinical studies
Teriflunomide went through
several stages of trials, and was
approved based on safety and
effectiveness data from two
large studies. In one, called the
TEMSO study, two different
doses of teriflunomide reduced
relapses and disease activity
on MRI scans significantly
more than placebo in 796
people with relapsing MS
over two years (The New
England Journal of Medicine,
2011;365:1293).
In the TOWER study, when
compared with placebo, two
dosing levels of teriflunomide
reduced relapses in 1,169
people with relapsing MS.
The higher dose— 14 mg—
also slowed progression of
disability.
Further research
Research continues on
teriflunomide, including one
investigating its use in people
at high risk for developing
MS. Such studies will help to
clarify teriflunomide’s role in
managing MS.
“We are greatly encouraged
to see a new oral therapeutic
option become available
to people living with MS,”
remarked Dr. Bruce A. Cohen,
(Northwestern University),
incoming chair of the Society’s
National Medical Advisory
Committee. n
