Swiss firm Novartis today announced that it has contacted regulators regarding the safety of the 100mg dose of its recently approved Type II diabetes drug, Galvus (vildagliptin).
According to the company's latest research, the 100mg once daily dose causes higher levels of an enzyme associated with liver damage than administering 50mg twice daily. As such, the company has proposed amendments to the drug's prescribing information and has contacted regulators to discuss the data.
While the drug was only approved in the EU towards the end of September and has yet to reach patients, it is currently available in Brazil and Mexico in both the 50mg and 100mg form.
US approval has been delayed due to an 'approvable letter' issued by the US Food and Drug Administration (FDA) in February this year, requesting further information regarding "skin-related findings" in pre-clinical studies in primates. At present, the company does not expect to submit additional data before the end of 2009.
The recent analyses that prompted today's announcement illustrated a known imbalance in the levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which becomes more prominent with the 100mg once-daily dosing regime.
Using the yard stick of enzyme levels greater than three times the upper limit of normal (ULN), results showed that 0.86 per cent of patients on the 100mg once-daily dose, 0.34 per cent of those taking the 50mg twice daily dose and 0.21 per cent of those taking 50mg once a day were found to have such elevated levels.
The 50mg a day dosage elevated enzyme incidence was similar to the 0.20 per cent from a comparator group of patients taking metformin, a thiazolidinedione (TZD), a sulfonylurea or a placebo.
As to whether today's news will prompt Novartis to drop the 100mg dose altogether, a company spokesperson told in-PharmaTechnologist.com that this "is being discussed with regulatory agencies, but we made a clear statement today to recommend using the 50 mg once daily and 50 mg twice daily dosing."
Novartis also today announced trial results reaffirming Galvus' efficacy against a TZD. In combination with metformin, the drug showed equal efficacy to pioglitazone (the active ingredient in Takeda's Actos) with metformin, but crucially did not cause the weight gain associated with TZD medication.
The drug itself is a member of a new class known as DPP-4 inhibitors, and has been approved for use in the EU in combination with the most common oral diabetes medicines - metformin, a TZD or a sulfonylurea.
It works through a novel mechanism of action, targeting the dysfunction in the pancreatic islets that cause high blood sugar levels in people with Type II diabetes.
Novartis has also developed a single tablet combination drug, containing Galvus along with metformin, Eucreas, which was recommended for approval in the EU towards the end of September.
The drug has been recommended for use in Type II diabetes patients who are inadequately controlled with metformin alone or are taking Galvus and metformin separately.
As to whether the combo pill will be affected by the safety issues presented today, Novartis spokespeople admitted that the proposed changes to the Galvus labelling will impact the label for Eucreas, but that "Eucreas is a separate issue that will be discussed with regulators after the Galvus monotherapy issues are resolved," in-PharmaTechnologist.com was told.