Teva Neuroscience, Inc. and Active Biotech
- Oral medication; 0.6 mg taken once daily. It has
been granted Fast Track status by FDA.
- Laquinimod is being studied in RRMS. Although
its exact mechanisms of action are unknown, it is
an immunomodulator, apparently through its
effects on cytokines and interleukins. It enhances
T-regulatory cell activity, which reduces Th1-
inflammatory T-cell activity. It also appears to
reduce white blood cell penetration of the central
nervous system (CNS).
- In addition to its immunomodulatory actions,
laquinimod increases levels of the brain-derived
neurotrophic factor (BDNF), possibly contributing to
neuroprotection in MS patients. BDNF is a protein
found in the brain that helps to support nerves and
their development. It also appears to prompt a
neuroprotective response fromcells within the CNS.
- The Phase III ALLEGRO study of 1,106 individuals
with RRMS has been completed. Compared to
placebo, laquinimod reduced the annualized
relapse rate by 23 percent and the progression of
disability by 36 percent. It also reduced T1-
hyperintense lesions by 27 percent, new
gadolinium-enhancing lesions by 37 percent, new
T2 lesions by 30 percent, and brain atrophy by
- The BRAVO Phase III trial is a global, 24-month,
double-blind study with 1,300 participants
designed to evaluate laquinimod's efficacy, safety,
and tolerability versus placebo. It will also provide
risk-benefit data for laquinimod versus Avonex.
Outcome measures are relapse rate, accumulation
of disability, and disease activity onMRI. In August
2011, the sponsors announced that the study had
failed to achieve its primary goal of reducing the
annualized relapse rate, although there may be a
trend in that direction if a subset of the data is
adjusted for differences inMRI characteristics at
the start of the study. Further analysis is ongoing.
- A three-year Phase III study of 1,332 individuals
with RRMS who completed the BRAVO study is
scheduled for completion in June 2013. It will
evaluate laquinimod's long-term safety, tolerability,
and effect on disease course.