- AstraZeneca's Type 2 diabetes drug Farxiga reduced the risk of cardiovascular death or hospitalization for heart failure by 17% compared to placebo, according to full results from a large cardiovascular outcomes trial presented Saturday at the American Heart Association's Scientific Sessions conference.
- While those data proved statistically significant, Farxiga didn't hit on the trial's other co-primary endpoint: lowering the risk of major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, heart attack or stroke. AstraZeneca noted there were fewer MACE events in the Farxiga arm, and that its drug achieved the primary safety endpoint of non-inferiority versus placebo.
- The British pharma intends to file data from the DECLARE-TIMI 58 study with regulators in the first half of 2019 in a bid to secure an expanded label. Farxiga sales totaled $994 million over the first nine months of 2018, a 32% increase year over year by constant exchange rates.
Despite headwinds in the overall diabetes drug market, AstraZeneca has been able to carve inroads for Farxiga (dapagliflozin). In the U.S., company leadership explained that "improved competitiveness across healthcare plans" helped spur 24% year-over-year sales growth during the first nine months of 2018.
To that point, Farxiga has been able to avoid some of the setbacks seen with other members of the SGLT2 inhibitor class. A major account last year cut Eli Lilly and Boehringer Ingelheim's Jardiance (empagliflozin) from its 2018 formulary — though the drugmakers expect that decision will be reversed in January. Meanwhile, Johnson & Johnson's Invokana (canagliflozin) carries a black box warning for lower limb amputations and has suffered lower sales lately due to increased discounts, rebates and competition.
Farxiga still has room for growth, however. Data from Iqvia and Leerink indicates weekly total prescriptions were about the same for Farxiga and Invokana, falling somewhere between 40,000 and 60,000, as of Nov. 2, while Jardiance prescriptions sat just above 81,000.
The manufacturers behind each of these drugs have turned to large cardiovascular outcomes trials both to meet a regulatory requirement and to — hopefully — gain a competitive edge. Results from the EMPA-REG study of Jardiance, for instance, supported a label expansion for reducing the risk of cardiovascular death in adult patients with Type 2 diabetes and cardiovascular disease.
EMPA-REG enrolled more than 7,000 patients, all with established cardiovascular disease, and took around five years to complete. DECLARE-TIMI 58 ran for a similar amount of time, but enrolled more than 17,000 patients, with 40% of them having established cardiovascular disease and 60% not.
"The strength of this trial is it's a much broader population than in the other two big outcome trials," Rudd Dobber, president of AstraZeneca U.S. told Biopharma Dive, adding that DECLARE-TIMI 58 had "a more real life patient population, the patient population which will end up in the office of general practitioners, versus the high-risk and very sick patients," which other trials enrolled to a larger degree.
While the miss on MACE reduction was a disappointment, Dobber said his company believes success on the other co-primary endpoint will go a long way with payers.
"Payers are very keen to understand better what this class of drugs, and especially Farxiga, can do, and therefore we expect that from a competitive position we're even better equipped moving forward with this unique set of data in order to either to maintain our [existing formulary positions] or to move into new formularies."
Additional data from the study found renal events were less common in the Farxiga arm than the placebo arm, 4.3% versus 5.6%, as was death from any cause, at 6.2% versus 6.6%. Conversely, cases of diabetic ketoacidosis were more common for Farxiga-treated patients. And so were genital infections that were deemed serious or that led to discontinuation of the treatment regimen.