Genzyme, a subsidiary of Sanofi has met primary endpoint in ENGAGE, the first phase III trial of its investigational oral therapy, eliglustat tartrate, in previously untreated patients with Gaucher disease type 1. Patients treated with eliglustat tartrate had a statistically significant improvement in spleen size at nine months, compared with placebo.

Spleen volumes in eliglustat tartrate treated patients decreased from baseline by a mean of 28 per cent versus a mean increase of two per cent in placebo patients, for an absolute difference of 30 per cent (p<0.0001). In addition, all secondary endpoints were met, including improvements in haemoglobin levels and platelet levels, as well as liver volumes compared with placebo-treated individuals.

The initial safety analysis from ENGAGE suggests that eliglustat tartrate was well tolerated. There were no serious adverse events reported in the primary analysis period and no clinically meaningful differences in the related adverse events reported between the two treatment groups.

“The efficacy and safety data from our ENGAGE trial are consistent with what were observed in our phase II study, continuing to suggest that eliglustat tartrate is a potent, well tolerated oral compound that may become a meaningful option for patients and physicians,” said Genzyme president and chief executive officer, David Meeker, MD. “The development of eliglustat tartrate has been underway for more than a decade and is the largest clinical programme ever focused on Gaucher disease, demonstrating our ongoing commitment to innovation on behalf of this community.”

The results from ENGAGE study will be presented at the Lysosomal Disease Network WORLD meeting, from February 12-15, 2013, in Orlando, Florida. Top-line data from Genzyme’s second Phase 3 registration trial, ENCORE, are expected to be presented in early 2013.

The company is developing eliglustat tartrate, a capsule taken orally, to provide a convenient treatment alternative for patients with Gaucher disease type 1, and to provide a broader range of treatment options for patients and physicians to achieve individual therapeutic goals. Currently, Genzyme’s Cerezyme (imiglucerase for injection), the standard of care for patients with Gaucher disease type 1, is administered through intravenous infusions.

ENGAGE is a randomized, double-blind, placebo controlled study in treatment-naïve patients with Gaucher disease type 1 and evaluated the efficacy, safety and pharmacokinetics of twice-daily dosing of eliglustat tartrate in 40 patients untreated for at least six months. The study had a primary efficacy endpoint of improvement in spleen size in individual patients treated with eliglustat tartrate compared with treatment with placebo, after the nine month study period. Patients were stratified at baseline by their spleen volume. Thirty-nine out of 40 study participants completed at least nine months of treatment. One patient in the eliglustat treated group discontinued at six months for personal reasons. At the end of nine months, patients who were on placebo were transitioned to eliglustat tartrate. After the primary analysis period concluded, all 39 patients chose to remain on treatment. Eighteen medical centres in 12 countries in North America, South America, Europe, Asia and the Middle East are participating in this study.

Genzyme previously reported that the 12-month phase II trial had met its primary composite endpoint: a clinically meaningful response in at least two of three endpoints (improvements in spleen size, haemoglobin and platelet levels) in individual patients. All patients in the ongoing phase II trial have been on treatment for at least five years.

Genzyme is currently completing the second phase III registration study, ENCORE. ENCORE is a randomized, open-label study for adult patients with Gaucher disease type 1, designed to compare eliglustat tartrate to Cerezyme. One-hundred sixty adult patients were enrolled in this trial. A third trial, known as EDGE is also fully enrolled, and compares once-daily with twice-daily dosing of eliglustat tartrate. Combined, these trials represent the largest clinical programme ever focused on Gaucher disease, with participating sites in over 30 countries. In total, more than 370 patients are enrolled in these studies.

Gaucher disease is an inherited condition affecting fewer than 10,000 people worldwide. People with Gaucher disease do not have enough of an enzyme, ß-glucosidase (glucocerebrosidase) that breaks down a certain type of fat molecule. As a result, lipid engorged cells (called Gaucher cells) amass in different parts of the body, primarily the spleen, liver and bone marrow. Accumulation of Gaucher cells may cause spleen and liver enlargement, anaemia, excessive bleeding and bruising, bone disease and a number of other signs and symptoms. The most common form of Gaucher disease, type 1, generally does not affect the brain.

Eliglustat tartrate, a novel glucosylceramide analogue given orally, is designed to partially inhibit the enzyme glucosylceramide synthase, which results in reduced production of glucosylceramide. Glucosylceramide is the substance that builds up in the cells and tissues of people with Gaucher disease. In preclinical studies, the molecule, developed with James A Shayman, MD, from the University of Michigan, has shown high potency and specificity. Based on its mechanism of action, which is independent of genotype, eliglustat tartrate may be a potential therapy for all patients with Gaucher disease type 1. Initiation of the phase II and III studies of eliglustat tartrate in Gaucher disease followed an extensive pre-clinical research effort and a phase I programme.

Approximately 15 per cent of patients have developed IgG antibodies to the infused enzyme. These patients have a higher risk of hypersensitivity reaction. Therefore periodic monitoring is suggested; caution should be exercised in patients with antibodies or prior symptoms of hypersensitivity. Symptoms suggestive of hypersensitivity occurred in 6.6 per cent of patients, and include anaphylactoid reaction, pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension. Reactions related to Cerezyme administration have been reported in less than 15 per cent of patients. Each of the following events occurred in less than two percent of the total patient population. Reported adverse events include nausea, vomiting, abdominal pain, diarrhoea, rash, fatigue, headache, fever, dizziness, chills, backache and tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture.

Genzyme has pioneered the development and delivery of transformative therapies for patients affected by rare and debilitating diseases for over 30 years. As a Sanofi company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients.