The sodium-glucose cotransporter-2 (SGLT-2) inhibitor Jardiance (empagliflozin; Boehringer Ingelheim/Eli Lilly) is expected to experience a significant increase in uptake in the type 2 diabetes market after the presentation of its much-anticipated cardiovascular (CV) outcomes data at the 51st European Association for the Study of Diabetes Annual Meeting in Stockholm, Sweden. The results from Jardiance’s dedicated cardiovascular outcomes trial (CVOT), EMPA-REG OUTCOME, showed a statistically significant reduction in the risk of CV death and all-cause mortality compared to placebo when used in addition to the standard of care. The results of EMPA-REG OUTCOME, a three-year trial that enrolled 7,020 type 2 diabetes patients at increased risk of CV events, represent a landmark in the treatment of type 2 diabetes, as Jardiance becomes the first antidiabetic to demonstrate a reduction in CV-related death in a dedicated outcomes trial. Previous CVOTs for other antidiabetic drugs only demonstrated that the therapies did not increase CV risk in the enrolled patients. Jardiance’s positive outcome is particularly important given the inherent risk of CV events in type 2 diabetes patients, which will potentiate the drug’s potential revenues.
In the EMPA-REG OUTCOME trial, Jardiance demonstrated a 14% reduction in the 3-point major adverse cardiovascular event (MACE) primary endpoint of CV death, non-fatal heart attack, or non-fatal stroke. This result was driven by a 38% reduction in CV death, and Jardiance also demonstrated a 35% reduction in hospitalizations due to heart failure and a 32% reduction in all-cause mortality compared to placebo. These reductions were observed in both the 10mg and 20mg Jardiance treatment arms. The trial indicated that there was no statistically significant difference between Jardiance and placebo in reducing non-fatal heart attack, non-fatal stroke, or the secondary endpoint of 4-point MACE, which consisted of CV death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina. The results of the trial also indicated that no significant increases in fractures or incidences of diabetic ketoacidosis were observed in patients receiving Jardiance; these events have previously been subjects of US Food and Drug Administration safety alerts with the SGLT-2 inhibitor class.
Key endpoint data from the EMPA-REG OUTCOME trial
|Outcome||Difference between Jardiance (at 10mg and 20mg) and placebo (hazard ratio)|
|Primary endpoint (3-point MACE*)||0.86(p=0.03282)|
|Hospitalization for heart failure
|Secondary endpoint (4-point MACE**)
*Consisted of CV death, non-fatal heart attack, or non-fatal stroke.**Consisted of CV death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina.
|CV = cardiovascular; MACE = major adverse cardiovascular event; MI = myocardial infarction
|Source: Zinman et al., 2015|
The magnitude of the reductions in CV death and hospitalization due to heart failure attributed to Jardiance therapy will significantly boost the drug’s position in the type 2 diabetes treatment algorithm. Datamonitor Healthcare’s primary research indicates that Jardiance is predominantly used as a third-line therapy after metformin and a dipeptidyl peptidase-IV (DPP-IV) inhibitor such as Januvia (sitagliptin; Merck & Co). The results of the EMPA-REG OUTCOME trial are expected to boost Jardiance’s position to the second- or potentially first-line treatment setting, with the drug now likely to strongly compete with the DPP-IV inhibitor drug class as the therapy of choice in combination with metformin in the large population of middle-aged type 2 diabetes patients at high risk of CV events. Jardiance’s uptake is also likely to be increased following the addition of the drug to existing therapy in patients at a lower risk of CV events, as a pre-emptive measure. For these reasons, Jardiance and the wider SGLT-2 class are expected to gain considerable patient share from the DPP-IV inhibitor class, and Datamonitor Healthcare believes this will result in the SGLT-2 inhibitor class replacing the DPP-IV inhibitor class as the most valuable class of non-insulin antidiabetics.
Data from the EMPA-REG OUTCOME trial also give Jardiance a substantial advantage over its direct in-class competitors, and Datamonitor Healthcare expects it to replace Invokana (canagliflozin; Johnson & Johnson/Mitsubishi Tanabe) as the leading SGLT-2 inhibitor brand. This will be achieved by capturing a significant share of the SGLT-2 inhibitor-naïve patient group, rather than from the switching of patients from rival brands within the class. Jardiance’s position in the drug class is further strengthened by the fact that the data confirming if the positive impact on CV outcomes is a class effect will not be available for at least two years. Data from the CVOTs investigating Jardiance’s two key in-class rivals Invokana and Farxiga (dapagliflozin; AstraZeneca) are expected in 2017 and 2019, respectively. This provides Eli Lilly’s and Boehringer Ingelheim’s sales and marketing teams with a considerable time period in which to promote Jardiance’s combined advantages on blood glucose levels and CV outcomes without direct competition.