A boxed warning for increased risk of leg and foot amputations will be added to the label of Johnson & Johnson’s (J&J’s) Type 2 Diabetes (T2D) drug, Invokana (canagliflozin).
This adds to the growing list of drawbacks in patients taking sodium-glucose cotransporter-2 inhibitors (SGLT-2Is), the newest T2D drug class, including reported cases of dehydration and ketoacidosis.
The drug class is unique as SGLT-2Is lower blood glucose levels in an insulin-independent manner, and harbour numerous non-glycemic advantages such as weight loss and a reduction in systolic blood pressure. Specifically, the inhibition of sodium-glucose cotransporter-2 (SGLT-2) hinders glucose reabsorption by the kidney.
SGLT-2Is were first launched in 2012, and include AstraZeneca’s Forxiga (dapagliflozin), J&J’s Invokana, and Eli Lilly / Boehringer Ingelheim’s Jardiance (empagliflozin). Currently, Jardiance has a distinct advantage in the SGLTI space as a result of positive outcomes from the EMPA-REG OUTCOME clinical trial, which showed that the drug successfully decreased the risk of heart attacks, strokes, and cardiovascular-related death in T2D patients.
The FDA has recently concluded that Invokana requires a boxed warning for its increased risk of leg and foot amputations. The decision comes after the regulatory body reviewed data from two clinical trials involving Invokana treatment, CANVAS and CANVAS-R. Findings from these studies revealed that patients were approximately twice as likely to get a leg or foot amputation when taking Invokana compared to patients on placebo.
As such, GlobalData believes that a likely scenario to emerge from these recent events would be Forxiga and Jardiance stealing significant patient share from Invokana in the US.
The European Medicines Agency (EMA) has also recognised the increased risk for lower limb amputations in patients on SGLT-2Is, but has expanded its warning to encompass all drugs belonging to the class: Invokana, Forxiga, and Jardiance.
Despite concerns associated with SGLT-2Is, key opinion leaders (KOLs) interviewed by GlobalData continue to advocate for the use of SGLT-2Is, as they are largely successful in treating T2D patients who are unable to adequately control their glycated hemoglobin (A1c) levels.
GlobalData (2016). PharmaPoint: Type 2 Diabetes – Global Drug Forecast and Market Analysis to 2025, May 2016, GDHC128PIDR.