Eli Lilly said Monday that it will discontinue development of the experimental CETP inhibitor evacetrapib for the treatment of high-risk atherosclerotic cardiovascular disease (ASCVD) after stopping a Phase III trial early. The company noted that the ACCELERATE study will be terminated on the recommendation of an independent data monitoring committee due to insufficient efficacy. Shares in Eli Lilly fell as much as 10 percent on the news.
"We're obviously disappointed in this outcome, as we hoped that evacetrapib would offer an advance in treatment for people with high-risk cardiovascular disease," commented David Ricks, president of Lilly Bio-Medicines. The drugmaker indicated that the decision to end development of evacetrapib will result in a fourth-quarter R&D charge of up to $90 million, or approximately $0.05 per share.
The ACCELERATE study, which enrolled 12 095 patients, was designed to evaluate the efficacy and safety of evacetrapib in participants with high-risk ASCVD. The primary outcome measure was designed to be time to first occurrence of any component of the composite cardiovascular events of cardiovascular death, myocardial infarction, stroke, coronary revascularisation or hospitalisation for unstable angina. Eli Lilly said that a review by the data monitoring committee suggested that "there was a low probability the study would achieve its primary endpoint based on results to date."
The drugmaker clarified that the trial is not being stopped for safety findings, adding that it "will now conclude other studies in the programme." Eli Lilly noted that after further analysis, results of the ACCELERATE study will be presented at future scientific forums.
Study author Steven Nissen remarked "I don't think that the strategy of CETP inhibition is going to work," adding that "evacetrapib was as good a drug in terms of its biological effects as anything we've seen [and] if it didn’t work, it is very unlikely that any other drugs in the class will work." Analysts had projected revenue of $632.7 million for the therapy by 2020, if approved, while Leerink Partners analyst Seamus Fernandez suggested the drug could amass about $2.5 billion in sales in 2026.
Commenting on the news, Jefferies analyst Jeffrey Holford said the decision by Eli Lilly to discontinue developing evacetrapib "is a major negative surprise," while Evercore ISI's Mark Schoenebaum stated "we anticipate that investors will also likely read across negatively to [Merck & Co.], whose CETP inhibitor anacetrapib is also being studied in an outcomes trial with data expected in early 2017." However, S&P Capital IQ analyst Jeffrey Loo suggested that while the evacetrapib data "raises more uncertainty" about anacetrapib, it "doesn't necessarily mean [it] won't be efficacious." Merck is currently conducting a Phase III study of anacetrapib in about 30 000 patients, with analysts projecting potential sales of $567.2 million for the drug in 2019 and $858.6 million in 2020.
Merck stated that "we need to see the data to better understand Eli Lilly's decision to discontinue its CETP programme." The company added that it "continues to believe that anacetrapib has the potential to be an important treatment in the management of atherosclerosis," with analyst Sam Fazeli of Bloomberg Intelligence suggesting Merck is relying more heavily on anacetrapib to become a success than Eli Lilly's portfolio does on evacetrapib.
Meanwhile, RBC Capital Markets analyst Michael Yee suggested that companies that are developing or marketing PCSK9 inhibitors may benefit from the failure of evacetrapib. The analyst indicated that CETP inhibitors were the primary competitive threats to the PCSK9 inhibitor class, which includes Amgen's Repatha  (evolocumab), Sanofi and Regeneron Pharmaceuticals' Praluent  (alirocumab) and Esperion Therapeutics' therapy ETC-1002 (bempedoic acid), which is in late-stage development.
For additional analysis, see FirstWord Lists – Eli Lilly scraps evacetrapib: the key questions and conclusions .