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AstraZeneca and BMS’ Forxiga Gain Regulatory Approval in Europe

Updated: 8/14/21 10:00 amPublished: 12/31/12

On November 14, the European Commission approved AstraZeneca and Bristol-Myers Squibb’s Forxiga (dapagliflozin) for type 2 diabetes throughout the European Union. Forxiga is an SGLT-2 inhibitor, the first drug of its type to be approved for use anywhere in the world. Like other SGLT-2 inhibitors, Forxiga works by allowing excess glucose to escape the body through urine (see learning curve in diaTribe #24). The drug works in a glucose-dependent way, meaning more glucose will be excreted when blood sugar levels are higher. In trials, patients using dapagliflozin typically reduced their A1c by an average of 0.8% to 1% in trials lasting a year (this is from a starting A1c of 8.5% before the trial began). Urination of excess glucose also means losing some excess calories each day, and indeed, participants in clinical trials lost a few pounds on average and saw a small drop in blood pressure.

Forxiga is a once-daily pill and can be taken either alone or in conjunction with other type 2 diabetes medications. We are particularly excited about the combination of SGLT-2 inhibitors with other diabetes medications in a single pill (fixed-dose combinations), which may occur in the future – examples include metformin and DPP-4 inhibitors (e.g., Januvia, Onglyza, and Tradjenta). Research suggests that the addition of an SGLT-2 inhibitor could potentially benefit patients on any kind of pre-existing treatment since its the way it works is distinct from that of other medications. AstraZeneca and BMS have yet to announce specifics regarding Forxiga’s cost, launch timeline, or reimbursement options in Europe.

Forxiga’s most common side effect is urinary and genital tract infections, which should be relatively easy to treat should they occur. Regulatory agencies have also raised some concerns regarding a potential increased risk of bladder and breast cancer and potential damage to the liver. These concerns ultimately led the FDA to deny dapagliflozin approval in the United States in January of this year (see new now next in diaTribe #39), although AstraZeneca and BMS have resubmitted dapagliflozin to the FDA with a new decision expected in mid-2013. The European Commission has also acknowledged these potential safety risks, but they judged that the potential benefits of Forxiga outweighed the risks and so recommended these concerns be assessed in post-approval clinical trials.

The new year could see the approval of multiple new SGLT-2 inhibitors in both the United States and Europe. J&J has submitted Invokana (canagliflozin) to regulators in both regions with an eye toward approval in 2013. The FDA will hold an advisory committee meeting on January 10 to discuss Invokana (we’ll be there!), and a decision from the Agency is expected this coming March. Pfizer’s ertugliflozin and Eli Lilly and Boehringer Ingelheim’s empagliflozin are two other SGLT-2 inhibitors that are currently in phase 3 trials, although it’s not clear when the companies expect to submit these for approval. Lexicon also has an SGLT-1/SGLT-2 dual-inhibitor that will begin phase 3 studies in early 2013; this drug works by a slightly different mechanism that prevents some glucose from being absorbed from the intestines in addition to allowing glucose to be excreted in the urine. We look forward to learning much more about the advantages and optimal use of this drug class as it comes to market in the coming years. –AW/JD

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