Date: 2016-03-03
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the the Lysosomal Disease Network 12th Annual WORLDSymposium™ 2016
Company: Protalix BioTherapeutics (Israel)
Product: PRX-102 (alpha-galactosidase-A)
Action
mechanism: enzyme replacement therapy. PRX-102 is the Company's proprietary plant cell-expressed, chemically modified recombinant alpha-galactosidase-A enzyme in development as a long-term enzyme replacement therapy (ERT) for the treatment of Fabry disease.
Disease: Fabry disease
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial details:
Latest
news: * On March 3, 2016, Protalix BioTherapeutics announced that positive interim data from the Company's phase I/II dose-ranging clinical trial of PRX-102 for the treatment of Fabry disease will be presented on March 3, 2016 at 3:15 PM PT at the Lysosomal Disease Network 12th Annual WORLDSymposium 2016 in San Diego. Dr. Hughes will be presenting interim results from the global, open-label, phase I/II dose-ranging trial. In the trial, 18 naïve male and female patients (11 male and 7 female) were enrolled across three dosing cohorts of 0.2 mg/kg, 1mg/kg and 2mg/kg for which intravenous infusions were administered every two weeks, with six and twelve month initial efficacy follow-ups. Clinical Data on Cardiac and Kidney Functions: Based on an analysis of kidney biopsies with randomized blinded scoring, PRX-102 demonstrated a major reduction from baseline in renal peritubular capillary Gb3 using the quantitative Barisoni Lipid Inclusion Scoring System (BLISS). The following table denotes the mean change from baseline at six months. 0.2 mg/kg Dosing Cohort Reductions of plasma Lyso-Gb3 and plasma Gb3 concentrations were also observed at six months. For the 0.2 mg/kg cohort, males (n=4) demonstrated a -72.2 ng/mL and a -3.9 µg/mL change, respectively. For the 1.0 mg/kg cohort, males (n=4) demonstrated a -67.6 ng/mL and a -5.4 µg/mL change, respectively. A meaningful reduction in the total score of Mainz Severity Score Index (MSSI), which looks at general, neurological, cardiovascular and renal parameters, was demonstrated in both the 0.2 and 1.0 mg/kg dosing cohorts at six months. Safety Data: The safety analysis for adverse events represents a total of approximately 15 patient years (n=18). PRX-102 was well tolerated, with the majority of events being mild and moderate. Only one of the 18 patients evaluated for safety experienced a related serious adverse event of hypersensitivity and was discontinued per protocol. There was a low incidence of treatment-induced anti-drug antibodies (ADA) with low titers that are reduced by one year of treatment. Only 3 out of 18 patients had treatment induced ADA in at least one visit (2 in the 0.2mg/kg dose group; one in the 1mg/kg dose group). Two patients of the 0.2mg/kg dose group had neutralizing antibodies, 1 of which was positive only in 2 out of 8 samples. Overall, PRX-102 showed a favorable trend in kidney function, stable cardiac function and reduction in kidney peritubular capillaries, plasma Gb3, Lyso-Gb3 and MSSI score. Enrollment in the phase I/II clinical trial of PRX-102 was completed in February 2015. All patients that completed the trial opted to continue to receive PRX-102 in an open-label extension study. The Company expects to report data on the 2mg/kg dose and additional interim 12 month data and full 24 clinical trial results throughout 2016 and 2017 at various medical meetings and symposia. The Company filed a Special Protocol Assessment (SPA) with the FDA for its planned phase 3 trial and expects to commence the trial in the first half of 2016.
0.2 mg/kg Dosing Cohort Percentage Reduction of Gb3
Overall (n=5) 75.5 %
Male (n=3) 82.2 %
Female (n=2) 65.4 %
1.0 mg/kg Dosing Cohort Percentage Reduction of Gb3
Overall (n=4) 86.5 %
Male (n=3) 89.6 %
Female (n=1) 77.3 %
In general, the leading causes for death of Fabry patients include cardiovascular disease and renal failures. All patients that participated in the trial exhibited stable cardiac and kidney function as measured by mean left ventricular mass (LVM), left ventricular mass index (LVMI), ejection fraction (EF), estimated Glomerular filtration rate (eGFR) and urine protein. The table below sets forth the mean absolute values, at baseline, six and twelve months of treatment, including percentage changes, which were scored in a randomized blinded manner.
Timeframe LVM (gr) LVMI (gr/m2) EF (%) eGFR (mL/min/1.73m2) Urine Protein (mg/g creatinine)
Baseline 98 55.1 55.1 109.1 185.3
6 months 94.4 52.6 55.8 108.5 193.3
12 months 94.8 53 54.6 111.8 176.7
1.0 mg/kg Dosing Cohort
Timeframe LVM (gr) LVMI (gr/m2) EF (%) eGFR (mL/min/1.73m2) Urine Protein(mg/g creatinine)
Baseline 104.1 55.8 62.6 104.8 92.2
6 Months 101.1 54.1 57.4 106.6 101.2
Mean annualized eGFR slope for male patients was found to be 0.16 for the 0.2mg/kg and 0.72 for the 1.0mg/kg. The reduction in the eGFR slope suggests that PRX-102 has the potential to attenuate the symptoms experienced by patients suffering from renal disease, and may introduce other potential benefits to those patients.
