FDA panel endorses new heart failure warnings for key AZ diabetes med
- DPP-4 inhibitors, such as AstraZeneca’s Onglyza (saxagliptin) and Takeda’s Nesina (alogliptin), may be associated with an increased risk of heart failure, according to an FDA panel.
- In 2008, the FDA issued guidance requiring companies that manufacture diabetes drugs to show that the drugs do not increase cardiovascular (CVD) risk.
- When the FDA’s advisory committee looked specifically at Onglyza and Nesina, they found that neither of the drugs increases the risk of CVD death, stroke, or heart attack. However, there was a statistically significant increase in the risk of heart failure associated with Onglyza, as well as an increase in all-cause mortality that concerned FDA staff.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are an important part of the treatment armamentarium for diabetes. DPP-4 is the enzyme that removes incretin, which plays an important role in glycemic control, from the body. Incretin tells the body to produce insulin after food has been ingested. By inhibiting removal of incretin, DPP-4s enhance glycemic control. Another bonus: DPP-4s are not associated with hypoglycemia or weight gain.
While the increased risk of heart failure is most likely a DPP-4 class effect, there's a chance that this won't significantly affect product uptake in this class (though a new warning label regarding heart risks is likely on the horizon). The panel did not recommend new restrictions on prescriptions—a major relief to AstraZeneca, as some analysts predicted the near-blockbuster Onglyza could see its sales cut in half over the development.
"Given the absence of a serious safety issue for either Onglyza or Takeda's Nesina suggests that, barring an overtly negative signal in TECOS, growth of the DPP-4 class is likely to continue without a meaningful change in current prescribing trends," said Leerink analyst Seamus Fernandez in a research note reported by Reuters.