This year’s American Diabetes Association (ADA) meeting took place in San Diego, California from June 9th to June 13th. The event provides the setting for physicians, industry, and academia to come together to discuss all topics type 2 diabetes (T2D)-related. Among the announcements that were of particular interest were trial results for several current and emerging therapies.

Benefits of Novo Nordisk’s Xultophy compared with basal-bolus insulin: Xultophy, a fixed dose combination (FDC) of the long-acting insulin Tresiba and the glucagon-like peptide-1 (GLP-1) receptor agonist Victoza, demonstrated similar HbA1c reductions as a basal-bolus insulin regimen (insulin glargine U100 and insulin aspart), but also provided significantly lower rates of hypoglycemia and a decrease in weight. Approximately two-thirds of patients on Xultophy, reached an HbA1c target of < 7% while there was an 89% reduction in severe hypoglycemic events compared with basal-bolus insulin therapy. Furthermore, the Xultophy group required a lower daily dose of insulin versus the basal-bolus treatment arm. Xultophy is competing against Sanofi’s long-acting insulin/GLP-1 receptor agonist FDC Soliqua, a fusion of Lantus with Adlyxin. The widespread use of Lantus over Tresiba in the United States should result in strong physician willingness to prescribe Soliqua. However, Victoza’s dominance in the GLP-1 receptor agonist market, combined with its cardiovascular (CV) benefit, and the new efficacy data showcased during the ADA meeting, indicates that Soliqua will struggle to overtake Xultophy as the market leader for this FDC drug class.

Tresiba poses no increased heart risks compared with Lantus: Tresiba demonstrated no increased risk of major CV events compared to Lantus in the DEVOTE trial. This study in 7,367 high-risk T2D patients showed that Tresiba was non-inferior to Lantus for the primary endpoint of major adverse CV events. Results from the secondary endpoints of the trial showed a significant reduction in the rate of severe (40%) and nocturnal severe (53%) hypoglycemia with Tresiba versus Lantus (both p<0.001). Novo Nordisk can now highlight the fact that Tresiba poses no increased heart risks and that it has some advantages over the first-to-market long-acting insulin analogue Lantus.

Ertugliflozin meets primary endpoint in two Phase 3 studies: Merck and Pfizer announced that ertugliflozin had significantly reduced HbA1C levels when taken with Merck’s dipeptidyl peptidase-IV (DPP-IV) inhibitor Januvia, as well as when added to first-line T2D medication metformin. This is good news for ertugliflozin as interviewed experts believe that the majority of ertugliflozin use will occur as part of an FDC with Januvia, resulting from Januvia’s dominance in the DPP-IV inhibitor class. This, along with the use of DPP-IV inhibitors before sodium-glucose co-transporter-2 (SGLT-2) inhibitors in the treatment algorithm, could lead to significant uptake of an ertugliflozin/Januvia FDC. However, experts maintain that use of ertugliflozin as a monotherapy is likely to be minimal in the absence of significant price discounts to currently marketed SGLT-2 inhibitors.

Invokana reduces the composite measure of CV risks but increases risk of amputation: In the CANVAS CV outcomes trial, Invokana achieved a 14% reduction in the risk of the composite primary endpoint of CV mortality, nonfatal myocardial infarction, or non-fatal stroke versus placebo in patients with T2D at risk of or with a history of CV disease. This result was similar to that for the effect of Jardiance on the primary endpoint in the EMPA-REG CV outcomes trial. In 2015, Boehringer Ingelheim and Eli Lilly reported that Jardiance reduced the risk of the combined endpoint of CV death, non-fatal heart attack or non-fatal stroke by 14% when added to standard of care, in patients with T2D at high risk of CV events in the EMPA-REG CV outcomes trial. However, Jardiance cut the risk of death in EMPA-REG by 38%, compared to a 13% reduction for Invokana in CANVAS. And, Invokana was linked to a significantly higher risk of amputations than placebo in CANVAS, a safety concern that has led to a black box warning.

Kidney study for Jardiance: Last year Boehringer Ingelheim and Eli Lilly announced that Jardiance significantly reduces the risk of kidney disease progression in T2D patients with established CV disease. These findings were part of a pre-specified exploratory analysis plan of additional endpoints of the EMPA-REG trial. Outcomes revealed that compared with placebo recipients, patients who received Jardiance had a 55% reduction in the initiation of renal replacement therapies, such as dialysis. In addition, Jardiance patients had significant reductions in the levels of creatinine and showed a decreased risk of albuminuria. This data has now triggered the two companies to conduct a new, large clinical outcomes trial investigating Jardiance for the treatment of chronic kidney disease (CKD). The plan is to enroll approximately 5,000 people with CKD both with and without T2D. Currently there are no treatments available to specifically treat CKD which affects more than 10% of people worldwide. Thus, new treatments that may have the potential to help address this crucial medical need are highly sought after.

Sanofi reports results from a real-world observational study for Toujeo: New real-world data shows Toujeo may out perform its competition by reducing the risk of hypoglycemia in at-risk patients aged ≥65 years. The study compared the number of hypoglycemic events after switching treatment to Toujeo versus other basal insulins in a group of at-risk seniors diagnosed with T2D with documented hypoglycemia and similar blood sugar control. Findings from a six-month follow-up revealed patients who switched to Toujeo were 57% less likely to experience low blood sugar compared to the other groups who opted for Lantus, Levemir, and Tresiba. Senior patients with T2D are significantly more impacted by hypoglycemia and its consequences. This real-world data could help physicians in their clinical decision-making process. However, long-standing familiarity with Lantus among physicians and the efficacy of Tresiba may deter switching.

Praluent benefits T2D patients: Two studies showed that Sanofi/Regeneron Pharmaceuticals’ proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor Praluent benefits patients with T2D who use insulin and those with T2D who have mixed dyslipidemia, respectively. The first study found that that T2D patients taking Praluent along with statins, saw a 49% drop in low-density lipoprotein (LDL) cholesterol, compared with placebo. Of patients on Praluent, 80% achieved their LDL cholesterol goals on the 75 mg dose. The second trial found that Praluent in combination with statins lowered non-high-density lipoprotein (HDL) cholesterol by 32.5% in the high-risk group, who were treated for T2D with a variety of medications, including insulin. In both studies, patients taking Praluent showed an overall improved lipid profile, the drug was well-tolerated, and it did not interfere with glucose-lowering medications such as insulin.

For further detailed analyses on the T2D market please see: DRG’s Type 2 Diabetes | Disease Landscape & Forecast | G7 offering.

For a look at how endocrinologists believe semaglutide (oral and sc) and ITCA-650 will perform in the European T2D therapy market, download our executive briefing here.

For more insights and analysis on the metabolic and renal markets, follow @jkhanDRG.

 

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