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Galvus superior to Actos with regard to weight, says Novartis
New data show Novartis' DPP-4 inhibitor Galvus is as good as Takeda's Actos at reducing glycaemia in type 2 diabetes patients uncontrolled by high doses of standard metformin treatment, but unlike Actos it will not cause patients to gain weight.
The data from a 24-week randomised double-blind study conducted by Dr G. Bolli of University of Perugia have been submitted for publication to a diabetes and obesity journal but were presented during the European Association for the Study of Diabetes meeting in Amsterdam this week at a company satellite symposium.
Novartis Global Medical Director for Galvus (vildagliptin), Dr Martin Fitchett, said the study involved patients who had been uptitrated to at least 2g metformin daily but who still had inadequate glycaemic control with an HbA1c of at least 7.5% - above both the US target of 7 per cent and the European one of 6.5%. The trial randomised 295 patients to vildagliptin 100mg daily plus 2g or more of metformin, or to Actos (pioglitazone) 30mg daily plus metformin. Patients in both groups had a fasting plasma glucose (FPG) of 11mmol/L, a body mass index (BMI) of 32 and had been treated for diabetes for between six and seven years.
Results showed that after 24 weeks both drugs along with metformin reduced HbA1c by around a further 1% in patients with a baseline reading below 8.4% and by 1.5 per cent in patients whose baseline HbA1c was above 9%. "As expected most of pioglitazone's effects were on FPG whilst Galvus' effects on this were less marked. Most of the glycaemia-reducing effect with Galvus was driven by its action on prandial (mealtime) glucose levels," he commented. The mean reduction in FPG was 1.4 mmol/l with vildagliptin plus metformin and 2.1 mmol/l with piofglitazone plus metformin.
No weight gain for vildagliptin patients
There was virtually no weight change in patients receiving vildagliptin 100mg (+0.3kg) but patients receiving pioglitazone 30mg daily gained an average 1.9 kg over six months if their BMI was below 35 at baseline, and 2.6kg if they were more obese at the start of the study.
"There was no real difference in the overall reporting of adverse events and in the low incidence of discontinuation," he added. "This means that if a patient isn't reaching their glycaemic target with metformin, they would do just as well by adding Galvus as a thiazolidinedione but they will not gain weight." Patients are four times more likely to reach their target HbA1c if they receive both vildagliptin and metformin rather than metformin alone, he added.
Novartis is expecting to receive the go-ahead from European regulators to start marketing Galvus in the 27 countries of the EU, Iceland and Denmark very soon. The drug will be indicated in combination with metformin, a thiazolidinedione or with one of the sulphonylureas. The company received a positive opinion from the Committee for Medicinal Products for Human Use at the end of July; a time frame of up to 67 days is the usual interval before final approval.
The company had an approvable letter from the US Food and Drug Administration in February this year but was asked to provide further clinical trial data in patients with moderate to severe renal impairment. Trials have been designed and submitted for approval but Novartis has yet to receive the nod from the FDA to start conducting them. Data are unlikely to be available before 2009 at the earliest. By Olwen Glynn Owen
New data tout Galvus efficacy, Actos safety
Pharmaceutical companies vying for a slice of the fast-growing US$21 billion diabetes market have been talking up their products as the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) kicked off in Amsterdam.
Novartis presented new data at the EASD meeting confirming the "robust efficacy and tolerability" of Galvus (vildagliptin), the dipeptidyl peptidase-4 (DPP-4) inhibitor for type-2 diabetes that secured an approval recommendation from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) in July.
The data showed that patients with uncontrolled type 2 diabetes taking the standard oral therapy metformin were four times more likely to achieve recommended blood sugar levels when Galvus was added to their treatment than on metformin plus placebo.
In the study of 544 patients with type 2 diabetes who were inadequately controlled on metformin ("Dejager S, et al. Achievement of Glycemic Targets with Vildagliptin"), 35.5% achieved glycaemic control (HbA1c < 7.0%) when Galvus was added to the metformin treatment regimen, compared with 9.4% of patients who were given metformin and placebo, Novartis reported. Moreover, 54.1% of patients in a subset with a baseline HbA1c of less than 8.0% achieved glycaemic control after taking both Galvus and metformin, compared with 13.3% of these patients receiving metformin and a placebo.
HbA1c is a test that measures the average amount of sugar in the blood over the last two to three months. The American Diabetes Association recommends an HbA1c level of less than 7.0% to minimize the risk of severe complications including heart disease, blindness, amputations, nerve damage and kidney failure.
Other data presented at the meeting confirmed that Galvus was well tolerated in patients with mild renal impairment, a condition seen in about one-third of all type 2 diabetes patients, and delivered strong efficacy and tolerability in the elderly, the fastest growing group of type 2 diabetes patients, Novartis noted.
A new analysis of pooled data from 1,864 patients showed the safety and tolerability of Galvus in patients with predominantly mild renal (kidney) impairment was similar both to placebo and to patients without renal impairment, the meeting heard. In a pooled analysis of five monotherapy studies covering 238 patients with a mean age of 70 years, Galvus produced blood sugar reductions of 1.2% as measured by HbA1c, was well tolerated, and was associated with a low risk of hypoglycaemia.
The CHMP's positive opinion was for use of Galvus as an add-on to the most commonly prescribed oral antidiabetics, metformin, the thiazolidinediones and the sulfonylureas - the broadest indication awarded to a DPP-IV inhibitor in Europe so far. Glavus has fared less well in the US, where the Food and Drug Administration issued an eapprovable letter' asking for more information on the drug in February. Novartis expects to file the additional data with the FDA in 2009.
Actos cardiovascular safety - again
In the meantime, Takeda is maintaining the flow of data suggesting a favourable cardiovascular safety profile for its established type 2 diabetes treatment Actos - particularly in relation to the continuing rumblings over the safety of GlaxoSmithKline's rival blockbuster Avandia (rosiglitazone).
An observational study published in Pharmacoepidemiology and Drug Safety showed that Actos was associated with a 22% lower risk of hospitalization from acute myocardial infarction in patients with type 2 diabetes compared with rosiglitazone, Takeda said. The results were publicised just a few days after a meta-analysis in the Journal of the American Medical Association found that Actos actually reduced the rate of death, myocardial infarction or stroke in diabetics by 18%.
Conducted by researchers from Takeda Global Research and Development, the direct safety comparison with Avandia was based on a claims database of 29 911 eligible patients from a large US health insurer. The retrospective cohort study examined 14,807 patients who had taken Actos and 15,104 who had taken Avandia between 2003 and 2006. The two groups were well-balanced at baseline, with the exception of statin and fibrate use, which was higher in the Actos group (consistent with the higher prevalence of hyperlipidemia observed), Takeda noted.
After adjusting for all known factors influencing baseline risks, the Hazard Ratio for hospitalisation with acute myocardial infarction was 0.78 (95%CI: 0.63-0.96) in favour of Actos, i.e., a 22% lower risk than for rosiglitazone, the researchers reported.
These observations were consistent with the results of the landmark placebo-controlled PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events) study, Takeda pointed out, adding: "All studies conducted for the past 10 years, including those in both humans and animals, have shown no evidence that Actos is associated with an increase in risk of heart attack or stroke."
By Peter Mansell
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