Amicus
Therapeutics FOLD and GlaxoSmithKline plc GSK today announced the
6-month primary treatment period results from the first Phase 3 global
registration study (Study 011) of investigational oral migalastat HCl
monotherapy in males and females with Fabry disease who had genetic mutations
identified as amenable to migalastat HCl in a cell-based assay. Study 011
randomized a total of 67 patients to receive oral migalastat HCl 150 mg or
placebo on an every-other-day (QOD) dosing schedule during a 6-month,
double-blind primary treatment period.
Reduction of GL-3 Substrate in Kidney Interstitial Capillaries:
Globotriaosylceramide (GL-3) is the lipid substrate that accumulates in
tissues of patients with Fabry disease, most notably in the kidney. GL-3
clearance from the kidney interstitial capillaries has been used as a marker
of treatment effect in Fabry disease. The pre-designated primary endpoint of
Study 011 was a responder analysis evaluating the number of patients who
demonstrated a 50% or greater reduction in kidney interstitial capillary GL-3
after 6 months of treatment with migalastat HCl compared to placebo. During a
6-month open label follow-up period all patients received migalastat HCl. The
FDA has also indicated that it will consider the 12-month efficacy and safety
data from Study 011. The paired kidney biopsies from baseline and month 6 were
assessed by histological scoring using the published, quantitative Barisoni
Lipid Inclusion Scoring System with Virtual Microscopy (BLISS-VM).^1 This
methodology will also be utilized for the evaluation of the kidney biopsies at
month 12. Amicus and GSK remain blinded to the 12-month data.
In Study 011 patients with evaluable baseline biopsies, 13/32 (41%) in the
migalastat HCl treatment group demonstrated a 50% or greater reduction in
kidney interstitial capillary GL-3 after 6 months of study treatment versus
9/32 (28%) in the placebo group. This difference did not achieve statistical
significance (p=0.3) according to the pre-specified primary endpoint analysis.
In addition to the binary responder analysis reported above, a pre-specified
secondary analysis assessing the absolute percent change in kidney
interstitial capillary GL-3 from baseline to month 6 was performed. Taken
alone this analysis showed a median reduction of 41% in the migalastat HCl
group versus a median reduction of 6% in the placebo group (p=0.093).
To date, no drug-related serious adverse events have been observed. The most
common treatment emergent adverse events occurring in 10% or more of subjects
were (migalastat; placebo, respectively): headache (35%; 21%); fatigue (12%;
12%); nausea (12%; 9%); nasopharyngitis, or inflammation of the nose and
throat (15%; 6%); and parasthesia, or tingling sensation of the skin (9%;
12%). The 4 dropouts in this portion of the study were deemed by the
investigators to be unrelated to study medication.
The 6-month secondary endpoints in Study 011 continue to be analyzed and will
be presented at the Lysosomal Disease Network WORLD Symposium (LDN WORLD), to
be held February 12-15, 2013, in Orlando, Florida. Secondary endpoints include
urine GL-3 and renal function (iohexol GFR, eGFR and 24-hour urine protein).
Market News and Data brought to you by Benzinga APIs© 2024 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.
Comments
Loading...
Benzinga simplifies the market for smarter investing
Trade confidently with insights and alerts from analyst ratings, free reports and breaking news that affects the stocks you care about.
Join Now: Free!
Already a member?Sign in