PRAGUE, Czech Republic, May 2 /PRNewswire-FirstCall/-- Oxford GlycoSciences Plc (LSE: OGS, Nasdaq: OGSI) announces that a 36 month update on the OGT 918-001 monotherapy study data was presented at the 5th European Working Group on Gaucher Disease meeting in Prague today. Data were also presented on the switch/combination study (OGT 918-004).
The primary objective of this study was to evaluate Vevesca (OGT 918) as a monotherapy for the treatment of type 1 Gaucher disease at a dose of 100mg TID. The extended use data on the 13 patients remaining in the trial to 36 months confirm progressive improvements in organ volume and haematological parameters observed at previous time points. Data were collected at 36 months on liver volume, spleen volume, haemoglobin concentrations and platelet counts. All four endpoints showed significant improvement over baseline using the "Last Observation Carried Forward" ("LOCF") statistical analysis at a significance level of p < or = 0.001. LOCF analysis is a more rigorous test as it retains all patient numbers (including drop-outs) in the mean scores.
The side effect profile was consistent with that previously described, with a continuous decline in prevalence and severity of gastrointestinal adverse events, a trend for mean weight returning to baseline and no further instances of peripheral neuropathy following the two cases described in 2000 (Cox et al., The Lancet, 29 April 2000).
One patient with cognitive decline was presented. This was described in the press release dated 24 April 2002.
PRAGUE, Czech Republic, May 2 /PRNewswire-FirstCall/ Oxford GlycoSciences Plc (LSE: OGS, Nasdaq: OGSI) today announces that data from its six month OGT 918-004 study to investigate the potential of oral treatment with Vevesca (OGT 918) in patients with Gaucher disease who have been receiving enzyme replacement therapy (ERT) (Cerezyme (R)) were presented at the 5th European Working Group on Gaucher Disease meeting in Prague. The study was conducted by Professor Ari Zimran, Director of the Gaucher Clinic at the Shaare Zedek Medical Centre, Jerusalem. Extension data from this study were also presented.
The objective of the -004 study was to explore the use of Vevesca (OGT 918) alone as an oral switch therapy and to investigate any benefits of co- administration with enzyme. In this study, 36 patients with type 1 Gaucher disease who had been receiving enzyme by regular intravenous infusions for at least two years were randomly assigned into three groups. One-third (12) of the patients changed to treatment with Vevesca (OGT 918) at a dose of 100mg three times daily ("switch group"), one-third received Vevesca (OGT 918) in addition to their usual regimen of intravenous enzyme ("co-administration group") and one-third remained on enzyme ("control group"). Liver and spleen volumes were measured by computerised tomography (CT) scanning at baseline and after six months; haematological changes and biochemical parameters were also followed. Quality of life was assessed at baseline, month three and month six using the standard SF-36 questionnaire with additional validated treatment- specific questions.
After six months there were no clinically significant differences between the groups. The primary efficacy measure, liver volume, showed a statistically significant improvement (reduction) from baseline to six months of -4.9% in the co-administration group compared to +3.6% in the control group. There were statistically significant differences from baseline in favour of the control group compared with the switch group for platelets and for both co-administration and control groups compared to Vevesca (OGT 918) for chitotriosidase. None of these were considered clinically important, and no patient became significantly anaemic or thrombocytopaenic. Analysis of Quality of Life data revealed that patients in the Vevesca (OGT 918) group reported significantly greater treatment convenience (p=0.028) and improvements (p=0.053) in overall treatment satisfaction compared to those who received enzyme, with none of the patients in the Vevesca (OGT 918) group reporting less satisfaction with treatment at month six relative to baseline.
Three patients withdrew from the randomised study; two from the switch group arm (one to start a family and also because of transient tremor of the right hand, one due to malaise and fatigue - subsequently attributed to infectious mononucleosis) and one from the co-administration group (due to diarrhoea). As in previously reported studies, the most frequent adverse events were gastrointestinal - all the patients who received Vevesca (OGT 918) experienced mild to moderate diarrhoea, but its prevalence decreased with time. Mild or moderate tremor was seen in the switch group and in the co- administration group but not in the control group. Analysis of electrodiagnostic testing (EDX) revealed abnormalities in all three groups that showed no clear relationship to therapy.
Of the 33 patients who completed the six month trial, 29 elected to enter an extension protocol to receive Vevesca (OGT 918), comprising ten from the switch group, ten from the control group and nine from the co-administration group. At the month 18 visit, more than 75% of these patients (22) were still receiving Vevesca (OGT 918) with withdrawals reflecting tolerability rather than efficacy. Over the 18 month period, none of the patients were returned to enzyme monotherapy because of deteriorating disease. One patient initially randomised to co-administration was withdrawn after 15 months because of a concurrent illness (multiple myeloma) and subsequently developed peripheral neuropathy considered secondary to progression of his concurrent disease.
Commenting on these results, Professor Ari Zimran said: "This first study of Vevesca (OGT 918) in patients on long-term enzyme replacement therapy shows encouraging results. No patient required rescue due to lack of efficacy and in those patients who tolerated treatment, clinical benefit is maintained up to 18 months."... |
