Novartis said that new clinical data involving Galvus (vildagliptin) has been accepted for publication in the journal Diabetes, Obesity and Metabolism. The data shows that this new oral medicine is as effective as one of the leading oral type 2 diabetes treatments and well tolerated.
Novartis has also provided a safety update to European regulators of pooled data showing numerically less frequent liver enzyme elevations in patients who took either 50 mg per day or 50 mg twice daily of Galvus compared to 100 mg once daily. As a result, Novartis has proposed changes to European prescribing information recommending use of the already approved 50 mg once-daily and twice-daily doses instead of 100 mg once-daily dose. Novartis will discuss the data and recommendations with other regulators.
The results of a new clinical study further confirmed the efficacy of Galvus in combination with metformin, long-standing oral type 2 diabetes treatments. This trial showed Galvus was as effective as pioglitazone, a member of the thiazolidinedione (TZD) class of diabetes medicines, when each was combined with metformin. Galvus was well tolerated and did not cause the weight gain that often occurs in patients taking a TZD.
In the 24-week study of 576 patients with type 2 diabetes, all of whom had inadequately controlled diabetes despite taking the oral medicine metformin, the addition of a 50 mg twice-daily dose of Galvus to metformin treatment reduced blood sugar levels as effectively as adding a 30 mg once-daily dose of pioglitazone to metformin.
Galvus was shown to be weight neutral, while the addition of the TZD was associated with weight gain (up to 1.9 kg after 24 weeks of treatment).
An updated analysis of pooled clinical trial data involving more than 8,000 patients treated with Galvus was finalized following the European Union approval on September 26 and included recently completed studies.
Novartis will discuss these data with the Committee for Medicinal Products for Human Use (CHMP), which is responsible for the review of medicines in Europe, and will seek a revision of prescribing information before Galvus is launched for sale in European markets.
The recent analysis further characterized a known imbalance in liver enzyme levels, which now appears more visibly in the higher Galvus once-daily dosing regimen. The results showed 0.86 per cent of Galvus patients taking the 100 mg once-daily dose, 0.34 per cent of those taking the 50 mg twice-daily dose and 0.21 per cent of those taking the 50 mg once-daily dose had elevations of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of greater than three times the upper limit of normal (3xULN).
At a 50 mg daily dosage, the incidence rate was comparable to the 0.20 per cent in the pooled comparator group of about 4,400 patients taking metformin, a TZD, a sulfonylurea or a placebo. The placebo rate was 0.40 per cent, and this was numerically higher than the Galvus 50 mg twice-daily dose. Elevated levels of these enzymes can indicate liver cell damage.
Novartis said it would continue working with the CHMP and other agencies to review these results and to revise prescribing information for Galvus, which is a member of a new drug class known as DPP-4 inhibitors. The currently approved European information recommends a 50 mg once-daily dose for use in combination with a sulfonylurea as well as a 50 mg twice-daily or 100 mg once-daily dose for combination use with either metformin or a TZD.
Galvus is currently available in Brazil and Mexico as both a 50 mg and 100 mg daily dose. In February 2007, Novartis received an "approvable letter" from the US Food and Drug Administration (FDA) and is in discussions with the agency.