BMS/AZ’s SGLT-2 inhibitor Farxiga (dapagliflozin) approved in the US – January 9, 2014

Yesterday, the FDA announced that it had approved BMS/AZ’s (soon to be just AZ’s) SGLT-2 inhibitor, dapagliflozin under the new trade name Farxiga. This approval (which came three days earlier than the expected PDUFA date of January 11), follows a positive 13-1 vote at Farxiga’s December 2013 Advisory Committee meeting. The FDA is requiring six post-marketing studies, including (i) the ongoing cardiovascular outcomes trial (CVOT); (ii) a double-blind, randomized, controlled assessment of bladder cancer in the CVOT; (iii) an animal study on Farxiga-induced urinary flow/rate and urinary composition changes on bladder tumor promotion in rodents; (iv and v) two clinical trials on PK, efficacy, and safety in children; and (vi) an “enhanced” pharmacovigilance program to monitor liver abnormalities and pregnancy outcomes.

The label indicates that Farxiga should not be used in people with moderate or severe renal impairment (eGFR below 60 ml/min/1.73 m²; this is more restrictive than J&J’s Invokana, which has a threshold of 45 ml/min/ 1.73 m²). Farxiga is also not recommended in people with active bladder cancer due to the imbalance of bladder cancers seen in clinical trials. We imagine that if results of the post-marketing bladder cancer assessment are positive, this restriction could be lifted; it is not a high number of people anyway, relatively speaking, but the clearer the label, likely the more open HCPs will be overall. Discussion at the Advisory Committee meeting suggested that panelists did not see bladder cancer as a big concern, and overall it is a positive that the FDA was able to approve the drug for the majority of people with diabetes.

Farxiga is now the second SGLT-2 inhibitor to be approved in the US. In Europe, under the trade name Forxiga, it has had a bit of a slow start due to the challenging reimbursement environment there (e.g., BMS/AZ withdrew Forxiga from Germany last month for this reason). Forxiga achieved $7 million in sales in its third full quarter on the market in Europe. Invokana has been approved in the US since late March 2013, where, according to J&J, it had captured 17% of the US new to brand prescription (NBRx) share in endocrinology in people with type 2 diabetes excluding insulin and metformin by the end of 3Q13 (making it the number one branded drug in NBRx share in that market). Analyst appear to expect approximately $100 million in sales for Invokana for 2013 and about $500-$550 million for 2014; these are estimates and J&J does not yet report revenue for Invokana, though we hope to see that change soon. We think Invokana's solid performance to date indicates that there is room in the SGLT-2 market for plenty of growth, especially when fixed-dose combinations begin launching (potentially within the next year or two). We would expect that bladder cancer concerns associated with Farxiga (real or not), as well as the potentially higher threshold for use in people with renal impairment, may mean that prescribers will reach first for Invokana before Farxiga. Of course, ultimately patient/provider utilization may come down to pricing and reimbursement and formulary issues, and we do not yet know how BMS/AZ plan to price Farxiga. 

-- by Jessica Dong and Kelly Close