Sanofi’s Genzyme says it will move ahead with regulatory filings for its orally-administered Gaucher disease therapy eliglustat tartrate after positive results in a second phase III trial.
Top-line data from the ENCORE study showed that eliglustat was as effective as Genzyme’s current injectable enzyme replacement treatment Cerezyme (imiglucerase), which brought in €633m ($846m) last year and is the top-selling drug for Gaucher disease, a rare inherited condition affecting fewer than 10,000 people worldwide.
Patients with Gaucher disease accumulate lipid engorged cells around the body, predominantly in the spleen, liver and bone marrow, which can lead to spleen and liver enlargement, anaemia, excessive bleeding and bruising and bone disease.
The ENCORE trial involved 160 patients with type 1 Gaucher disease who had been on enzyme replacement therapy for at least three years.
The results revealed that 84 per cent of patients on eliglustat had stable spleen volume, haemoglobin levels, platelet counts and liver volume for one year after randomisation, compared to 94 per cent of patients in the Cerezyme arm, with the difference deemed to be non-significant.
Meanwhile, Genzyme also reported updated results from the drug’s first phase III trial – called ENGAGE – after releasing top-line data last year.
The 40-patient study involved 40 treatment-naïve type 1 Gaucher patients and saw them achieve significant reductions in spleen size – reducing it by 28 per cent after nine months compared to 2 per cent with placebo.
Secondary objectives were also met, with haemoglobin counts down 1.2g/dL, platelet levels up 41 per cent and liver volume down 7 per cent compared to the control group.
The results were presented last week at the Annual Lysosomal Disease Network World Symposium in Orlando, Florida. A third study – EDGE – is ongoing and will examine whether the dosage of the drug could be reduced from twice- to once daily.
The new data puts eliglustat on track for filing this year with approval potentially coming in 2014. If it gets the green light is could became an important treatment for Gaucher disease, not only because it has a more patient-friendly administration but also because its mechanism of action differs from enzyme replacement therapy and the two therapies may eventually be used in combination.
Eliglustat acts at a level above the defective enzyme in Gaucher disease and reduces the amount of a toxic metabolite (glucosylceramide) that is the target of enzyme replacement therapy.
This substrate reduction mechanism is shared with Actelion’s oral Gaucher treatment Zavesca (miglustat), which is reserved for use only when enzyme replacement therapy is unsuitable and achieved sales of 85m Swiss francs ($92m) last year.
Genzyme maintains that eliglustat works in a slightly different way which means it is considerably more potent than miglustat.