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Tuesday, June 11, 2019

Trulicity heart data falls short for Lilly investors

  • Eli Lilly’s injectable diabetes drug Trulicity reduced the risk of heart attacks, stroke and cardiovascular death by 12% when compared to placebo, according to full data from the REWIND trial presented at the American Diabetes Association meeting in San Francisco. Investors, however, had been expecting a greater risk reduction.
  • Trulicity is the leading drug in its class of GLP-1 agonists, but is locked in fierce competition with two Novo Nordisk products, Victoza and Ozempic. Victoza’s cardiovascular outcomes trial previously revealed a similar-looking 13% reduction in risk.
  • Investors were counting on Trulicity reducing cardiovascular risk by about 20%, Cowen analyst Steve Scala wrote in a June 10 note to clients. Lilly shares fell more than 3% in early trading Monday.

Drugs to treat diabetes aim to reduce blood sugar levels. But because the main cause of death in diabetics is heart disease, regulators and insurers want to see clear signs treatments also improve cardiovascular health.
To confirm whether that benefit exists, regulators have asked for post-approval cardiovascular outcomes trials, which require thousands of patients monitored over years.
REWIND enrolled 9,901 patients receiving either Trulicity (dulaglutide) or a placebo, with both arms otherwise receiving standard of care treatment. Patients were followed for more than five years, with a primary endpoint combining the occurrence of non-fatal myocardial infarction or stroke, or cardiovascular death.
The 12% reduction in risk looks similar to the 13% scored by Victoza (liraglutide) in Novo’s LEADER trial. Lilly executives were quick to point out that Novo’s study enrolled patients only with established cardiovascular disease, while REWIND enrolled both those with established disease and those with risk factors for heart-related complications.
Further analysis revealed that in those with established cardiovascular disease, patients taking Trulicity saw a risk reduction similar to Victoza, 13%. Novo’s second GLP-1 agent, Ozempic (semaglutide), reduced risk by 26% in patients with established cardiovascular disease in the SUSTAIN-6 trial, although that was a smaller and shorter study.
Lilly executives said they are pursuing an addition to the Trulicity label that will allow its marketing campaigns to emphasize the cardiovascular benefit in both the established and high-risk cardiovascular populations. The 20% benefit for which investors were hoping would have given Trulicity a clear edge so, while positive, REWIND’s full results could mean a tougher marketing battle.
Trulicity’s big advantage over Victoza is once-weekly dosing versus once-daily. Novo has sought to counter this with once-weekly Ozempic, along with a once-daily oral version of semaglutide that is now under Food and Drug Administration review. The Ozempic label so far only highlights that there is no increased risk of cardiovascular events based on the SUSTAIN-6 trial.
Moreover, as competition heats up, decisions over which drug patients receive may depend less on efficacy and more on insurance coverage, especially since Victoza has been excluded from some formularies.
“We think the precise details are less important here given growth of the GLP-1 class is being driven by primary care physicians whose prescribing decisions are often less data driven and impacted by factors such as formulary positioning and the injection device,” Credit Suisse analyst Vamil Divan wrote in a June 10 note.
In the meantime, Lilly is seeking to bolster its diabetes pipeline by pushing through a new experimental agent, tirzepatide, which acts on both GLP-1 and a second hormone called GIP. The Indianapolis-based company presented data from Phase 2 trials of tirzepatide at ADA that showed numerically greater reductions in blood sugar levels and body weight than dulaglutide.
A 15mg once-weekly dose was associated with treatment discontinuations due to gastrointestinal side effects. However, trial investigators have developed a protocol that can reduce discontinuations, which will be used in the Phase 3 program. Lilly expects to have the first pivotal data by late 2020.

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