A trial investigating the ability of Eli Lilly’s Mounjaro (tirzepatide) to reduce the risk of cardiovascular issues has met its endpoints, though analysts were left underwhelmed by the degree of efficacy.
Eli Lilly is attempting to join fellow pharma companies with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) – drugs originally approved for treating diabetes – gaining expanded label expansions in cardiovascular indications.
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The company’s Phase III Surpass-CVOT trial (NCT04255433) pitted blockbuster medication Mounjaro against Trulicity (dulaglutide), the company’s other GLP-1RA that is already approved for reducing the risk of major adverse cardiovascular events (MACE).
The approximately five-year trial enrolled 13,299 patients who received once-weekly Mounjaro or Trulicity. The Surpass-CVOT study achieved its primary endpoint, with Mounjaro demonstrating noninferiority to Trulicity in reducing the three major adverse cardiovascular events (MACE-3)—cardiovascular death, heart attack or stroke.
Shares in Eli Lilly closed were down 0.8% in premarket trading today (1 August), though stock across most of the pharma industry was affected by US President Donald Trump doubling down on cutting prescription drug prices.
Overall, Eli Lilly’s Mounjaro – a dual agonist that works by mimicking both GLP-1 and GIP hormones – reduced MACE-3 by 8% compared to Trulicity, which only inhibits GLP-1. In the trial, Mounjaro also led to greater improvements in A1C, weight and cardiovascular biomarkers, showcasing its metabolic improvement credentials.
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By GlobalDataThe US drugmaker plans to submit data from Surpass-CVOT to global regulatory authorities by the end of this year.
Eli Lilly’s cardiometabolic health executive vice-president Kenneth Custer said: “The SURPASS-CVOT results show that Mounjaro preserved the cardioprotective benefit of Trulicity, a GLP-1RA, while providing additional benefits, including greater kidney protection and a reduced overall risk of death.
“These findings strengthen the case for Mounjaro as a potential front-line treatment for people with type 2 diabetes and cardiovascular disease.”
There has been much anticipation for Eli Lilly’s Surpass-CVOT readout, with investors keeping a close eye on whether the dual agonism of Mounjaro could provide a cardiometabolic advantage over already-approved GLP-1 therapies.
While detailed results will be presented at an upcoming conference in September, analysts at William Blair said investors will likely be disappointed by the current readout. Given its dual mechanism of action and already-proven efficacy, Mounjaro might have been expected to produce a superiority over Trulicity, rather than a non-inferiority outcome.
Citi analysts concurred, writing in a research note that it “misses the superiority scenario that many investors had hoped for”.
Comparisons are expected to Novo Nordisk’s Ozempic (semaglutide), which underwent a similar trial before winning US Food and Drug Administration (FDA) approval in reducing MACE in 2020. Ozempic produced a 26% risk reduction versus placebo in the SUSTAIN-6 trial (NCT01720446), only narrowly lower than Mounjaro’s value of 28% in the Surpass-CVOT study. Since Novo’s SUSTAIN-6 trial, higher doses of Ozempic have been approved, meaning its efficacy might be greater now.
Although Mounjaro fell short of analyst expectations, the study completion strengthens Eli Lilly’s lead over Novo Nordisk in the GLP-1RA arena. Zepbound – the brand name for tirzepatide in weight loss – and Mounjaro are projected to have higher sales than Ozempic and weight loss counterpart Wegovy by 2031, according to analysis by GlobalData. Last year, Eli Lilly’s sales grew 32% compared to 26% for Novo Nordisk.
