Forxiga, a SGLT2 inhibitor, approved in Europe for treatment of type 2 diabetes
Forxiga ( Dapagliflozin ) is the first SGLT2 ( sodium/glucose cotransporter 2 ) class drug. Forxiga has obtained marketing approval by the European Commission ( EC ) for the treatment of type 2 diabetes in Europe.
Forxiga tablets are approved as a once-daily oral medication in adult patients with type 2 diabetes to improve glycaemic control: as a monotherapy, when diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance; or in combination with other glucose-lowering medicinal products including Insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.
Forxiga is not indicated as a weight loss product or for the management of obesity or high blood pressure, and has only been studied for the treatment of type 2 diabetes.
Dapagliflozin works in the kidney by removing the extra glucose present in urine. It also helps in reducing the blood sugar levels, weight as well as blood pressure.
The drug is available in 5mg and 10mg doses for oral administration.
The EU approval for Forxiga was based on data received from 11 phase III clinical trials. The randomised, double-blind and placebo-controlled studies enrolled over 5,693 patients with type 2 diabetes internationally. The studies assessed the safety and efficacy of Forxiga in comparison with placebo.
The phase III studies met the endpoint of achieving HbA1c less than 7%.
The results also showed that Forxiga reduced body weight as well as blood pressure.
The adverse events found during the clinical studies included increase in blood creatinine, nausea, rash and dizziness.
Safety concerns with Forxiga identified in the clinical trials included an increased number of bladder and breast tumours in Dapagliflozin-treated patients, limited data available in patients above 75 years, the use in patients at risk of volume depletion, hypotension and electrolytes imbalances.
The CHMP, EMA Scientific Committee, assessed these concerns and found that they are satisfactorily addressed in the product information and in the risk management plan for Forxiga.
As the effects of Dapagliflozin are dependent on kidney function, the efficacy of the medicine is reduced in patients with kidney impairment. Therefore, the use of Forxiga is not recommended in patients with moderate to severe kidney impairment.
Overall there was no imbalance of malignancies between Dapagliflozin-treated patients and those on control. The unexpected finding of more bladder ( 0.16% as compared to 0.03% in the controls ) and breast cancers ( 0.40% as compared to 0.22% in the controls ) in Dapagliflozin-treated patients is of concern especially in the light of potentially long treatment periods and a possible widespread use.
Even though data from carcinogenicity studies in animals did not indicate a genotoxic or carcinogenic effect of Dapagliflozin, the CHMP considered it necessary to keep this potential risk under close observation and requested the applicant to conduct an epidemiological study with Dapagliflozin.
The potential risk of cancer will also be looked at in the planned cardiovascular outcome study further investigating potential cardiovascular risks of Dapagliflozin.
Source: EMA, 2012