UPSHER-SMITH DEBUTS POSITIVE RESULTS FROM GLOBAL PHASE 3 STUDY EVALUATING USL255 (EXTENDED-RELEASE TOPIRAMATE) IN EPILEPSY PATIENTS WITH REFRACTORY PARTIAL-ONSET SEIZURES
Maple
Grove, MN – December 9, 2013 – Upsher-Smith Laboratories, Inc. (Upsher-Smith) today presented
results from its global Phase 3 (PREVAIL) study of USL255 (extended-release
topiramate), showing that the investigational drug met its primary and
secondary endpoints for efficacy and demonstrated favorable safety and tolerability
in epilepsy patients with refractory partial-onset seizures (POS). The data
were presented for the first time at the American Epilepsy Society’s (AES) 67th Annual Meeting in Washington,
DC, December 6-10, 2013.
USL255 is a once-daily, broad-spectrum antiepileptic drug specifically
engineered to deliver a smooth pharmacokinetic (PK) profile. Upsher-Smith’s New
Drug Application for USL255 has been accepted for review by the U.S. Food and
Drug Administration (FDA).
Findings
presented at the meeting showed that USL255 was associated with a significantly
greater median percent reduction in weekly POS frequency compared with placebo
(39.5% vs 21.6%, P<0.001) after 11 weeks of treatment. The majority of
treatment-emergent adverse events (TEAEs) reported were mild to moderate in
intensity and generally resolved over time. Individual neurocognitive
adverse events were each observed at incidence rates of 2.4 percent or less in patients
taking USL255. Although ongoing, to-date 96.8 percent of patients who
completed the double-blind portion of PREVAIL elected to continue in a
year-long, open-label extension study of USL255.
“Topiramate is a well-known, effective agent for the treatment of a variety of
seizure disorders, but many patients experience challenging cognitive side
effects while taking the immediate-release formulation of the drug,” said Steve
Chung, M.D., Professor of Neurology at the Barrow Neurological Institute,
Phoenix and trial investigator. “The PREVAIL trial showed that
USL255, a once-daily
extended-release formulation of topiramate, is efficacious across a range of
seizure types and patient severity. This extended-release formulation appears
to be a new delivery system of a very effective compound. By improving the
delivery method, we hope to improve tolerability, which may lead to better
seizure control in patients.”
“We are pleased with the positive results seen in this study,” said William
Pullman, MB BS, BMedSc, PhD, FRACP, Chief Scientific Officer,
Upsher-Smith. “Our Phase 3 trial, PREVAIL, demonstrated that USL255 was
efficacious and well tolerated, particularly with respect to the low incidence
of cognitive side effects. These findings support the potential use of USL255,
an extended-release formulation of topiramate, as a treatment for patients with
seizure disorders.”
The
PREVAIL trial was a randomized, multicenter, double-blind, placebo-controlled,
parallel-group study designed to evaluate the efficacy and safety of USL255 as
adjunctive therapy in patients with refractory POS. The global Phase 3
study enrolled 249 patients at 66 centers. Additional findings presented at AES
include:
Efficacy Results
During
the three-week titration phase, USL255-treated subjects demonstrated a
significantly greater median reduction from baseline in weekly POS frequency as
compared with placebo-treated subjects (33.9% vs 8.6%, P<.001). This
significant treatment effect was sustained during the eight-week maintenance
phase (45.7% vs 22.1%, P=.001). USL255 significantly reduced POS frequency as
early as week one when compared with placebo and sustained this efficacy.
The
50 percent responder rate during the 11 weeks of treatment was also
significantly greater with USL255 compared with placebo (37.9% vs 23.2%,
P=.013).
USL255
significantly reduced median weekly complex partial seizure frequency (P=.001)
and was associated with a higher responder rate (P=.003). USL255 was shown
to be effective in both complex partial seizures (CPS) and partial secondarily
generalized seizures (PSG). USL255 was most effective in subjects taking more
than two antiepileptic drugs (AEDs) and demonstrated improvement, even in the
most refractory of patients (≥ 7 AEDs tried).
Treatment
with USL255 resulted in a significant improvement in time to seizure freedom
(P=.004), and a significantly higher percentage of subjects achieved seizure
freedom for at least 21 days prior to the last dose of study drug as compared
with placebo(16.1% vs 5.6%,
P=.006).
Tolerability
Results
About Upsher-Smith’s
Phase 3 (PREVAIL) Clinical Trial
PREVAIL
was conducted under a Special Protocol Assessment (SPA) agreement with the
FDA. More information about the trial is available at www.clinicaltrials.gov (NCT01142193).
An
open-label extension study to evaluate the safety of USL255 as adjunctive
therapy in patients with refractory POS who had participated in PREVAIL is
ongoing. The open-label extension study can be found by searching NCT01191086 on www.clinicaltrials.gov.
Upsher-Smith’s Epilepsy
Pipeline
Upsher-Smith’s
clinical development pipeline includes three investigational drugs that are
being studied for the management of seizure disorders. USL255 is an
investigational once-daily, extended-release topiramate for the management of epilepsy. The pipeline also includes
USL261, an investigational intranasal midazolam for the rescue treatment of
seizures in patients who require control of intermittent bouts of increased
seizure activity, often called seizure clusters, which
is the subject of an ongoing international Phase 3 clinical trial (ARTEMIS1) with
an open-label safety extension study. In addition, USL260
(tonabersat) is in early clinical development as a potential first-in-class
neuronal gap junction modulator.
About Upsher-Smith
Upsher-Smith,
founded in 1919, is an independent and privately-owned specialty pharmaceutical
company headquartered in Maple Grove, Minnesota that focuses on product growth
and innovation for branded and generic pharmaceuticals. Upsher-Smith has
a particular focus on developing therapies to assist people suffering from
central nervous system diseases and also markets products relating to
cardiology, dermatology, and women’s health. For more information, visit www.upsher-smith.com.
