Laquinimod Results Published: Oral Drug
Reduces Disease Activity in Phase 2 Study
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Medical Update Memo
July 3, 2008
SUMMARY
Treatment with oral laquinimod (Teva Pharmaceutical
Industries) reduced disease activity by 40.4%
compared with inactive placebo in a phase 2
study of 306 people with relapsing-remitting
MS*. Laquinimod is believed to affect the immune
attack on the brain and spinal cord that occurs
in MS. Giancarlo Comi, MD (Scientific Institute
San Raffaele, Milan) and colleagues, who originally
reported the results at the Annual Meeting
of the American Academy of Neurology in 2007,
now publish these results in the Lancet (2008;
371: 2085-92). A phase 3 study of laquinimod
is underway in 1,000 people with relapsing-remitting
MS.
Details
Multiple sclerosis involves immune-system
attacks against the central nervous system.
Currently approved therapies for MS involve
injections or infusions. Having an effective
therapy in pill form would be a big step forward
for people with MS. Laquinimod is an oral therapy
that is thought to shift the balance of immune
cells away from inflammation. The drug is related
in structure to linomide, which showed early
promise but in phase 3 clinical trials caused
significant adverse events including cardiac
toxicity.
Dr. Comi and colleagues randomly assigned
306 people with MS to receive placebo, .3 mg/day,
or laquinimod .6 mg/day. Participants underwent
monthly brain MRI scans and clinical examinations
from week 12 to week 36. The primary outcome
tested was the number of active lesions (areas
of active disease activity or damage) as observed
on MRI.
The cumulative average number of active lesions
was significantly reduced by 40.4% in the group
taking .6 mg compared with those taking placebo,
but no benefit was seen in the .3 mg group.
No significant reductions were seen in relapses;
however the study was not designed to detect
these differences.
Both doses were considered well tolerated,
and heart problems were not seen at either
dose. Increases in liver enzymes occurred in
23.4% of the .6 mg group, 33% of the .3 mg
group, and in 10.8% of the placebo group, with
two patients in the .3 mg group discontinuing
treatment due to these abnormalities. One patient
in the .6 mg group developed Budd-Chiari syndrome
(a partial blockage of blood outflow from the
liver) after one month on treatment. This person
had a pre-existing tendency toward blood clots,
and the authors note that the possibility that
such patients might be at increased risk of
serious adverse events should be explored in
further studies.
In an accompanying editorial, B. Mark Keegan,
MD, and Brian Weinshenker, MD (Mayo Clinic,
Rochester, MN), write that this study may have
been too short to reveal reductions in MS relapses,
and that the two-year, phase 3 study should
clarify this issue. They also suggest that
head-to-head studies are needed to directly
compare laquinimod with approved MS therapies
to determine if the convenience of oral therapy
is adequately matched by the drug's effectiveness.
With information from the National MS Society (USA)
ASK MS Information System Code: 1.4.2.ii
National Client Services
Medical Information and Education
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Disclaimer
The Multiple Sclerosis Society of Canada is an independent, voluntary health
agency and does not approve, endorse or recommend any specific product or therapy,
but provides information to assist individuals in making their own decisions.
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