The studies are the first to focus on use of PCSK9 inhibitors in patients with diabetes. Alirocumab, sold as Praluent, is expected to report its cardiovascular outcomes trial in early 2018.
A pair of studies unveiled early Sunday show the PCSK9 inhibitor alirocumab, sold as Praluent by Sanofi and Regeneron, benefits patients with type 2 diabetes (T2D) who use insulin and those with T2D who have mixed dyslipidemia. The results were presented at a symposium during the 77th Scientific Sessions of the American Diabetes Association (ADA), being held in San Diego, California.
Both studies are part of ODYSSEY, whose phase 3 results led to alirocumab’s FDA approval in July 2015. The first study presented, ODYSSEY DM-INSULIN, found that that patients with T2D taking alirocumab, along with the maximum tolerable dose of statins, saw a 49% drop in low-density lipoprotein (LDL) cholesterol, compared with those on placebo. Eighty percent of patients in the treatment arm achieved their LDL cholesterol goals on the 75 mg dose; others had their dose increased to 150 mg. (Results for patients with type 1 diabetes will be presented at a later date.)
The second trial, ODYSSEY DM-DYSLIPIDEMIA, found that alirocumab in combination with statins did outperformed usual care in lowering non-high-density lipoprotein (HDL) cholesterol by 32.5% in this high-risk group, who were treated for T2D with a variety of medications, including insulin. Improvements in non-HDL cholesterol can reduce heart attack risk, especially in this population. In the trial, 64% of patients in the treatment arm achieved LDL cholesterol goals with the 75 mg dose.
In both studies, patients taking alirocumab showed an overall improved lipid profile, and the drug was well-tolerated. The drug did not interfere with glucose-lowering medications—including insulin—or glycemic control.
The results come as Sanofi and Regeneron are locked in a patent dispute with Amgen, maker of the rival PCSK9 inhibitor evolocumab, and Sanofi is fighting Amgen in court to keep alirocumab on the market. Alirocumab’s more important news will come in early 2018, when Sanofi is expected to announce topline results of ODYSSEY OUTCOME, the 18,000-patient cardiovascular outcomes trial.
In April, Amgen presented results for FOURIER, the cardiovascular outcomes trial for evolocumab; while FOURIER met a composite endpoint for CV events, it failed to show a decrease in CV deaths, earning a poor reception from analysts who wondered whether payers would ease access for a drug with a wholesale price of $14,000 a year (alirocumab’s price is about the same). Amgen has pursued performance-based contracts and offered refunds if patients have a heart attack while taking it.
During Sunday’s session, presenters emphasized alirocumab’s safety data. Bertrand Cariou, MD, PhD, of the University Hospital of Nantes, France, cited a 2016 study he co-authored that found alirocumab thus far shows no evidence of a signal of new onset of diabetes. When FOURIER was presented April, cardiologist Eric Topol, MD, told the biotech news outlet Exome that evolocumab’s data showed a signal for new onset diabetes, but the study was not powered for it to be statistically significant. Amgen’s statement at the time said FOURIER identified no new safety concerns.
Cardiologists and endocrinologists have complained that payers have made access to PCSK9 inhibitors difficult, even for patients who seem to meet the criteria. Both groups of patients in the studies presented Sunday are at high risk of cardiovascular disease; in an interview with The American Journal of Managed Care®, officials with Sanofi said that value of alirocumab in safely reducing cardiovascular risk among the highest-risk patients—and particularly among those with diabetes—would be part of a message to payers.
“This shows our commitment to these patients,” said Sheldon Koenig, senior vice president, Global Head of Cardiovascular at Sanofi. “That’s one of the reasons why the ADA selected these studies to be presented (Sunday), these are the first studies of a PCSK9 inhibitor in patients living with diabetes.”
“A patient who has had a recent (cardiovascular) event is high risk,” said Jay Edelberg, MD, PhD, vice president, head of Cardiovascular Development and head, Global Cardiovascular Medical Affairs. “If that patient also has diabetes, that patient has the highest risk we know.” With these studies, he said, there is now evidence that the highest risk patients can be treated with something that is effective, and “very, very safe,” he said.
The studies represent a theme of this year’s meeting: an overlap of the fields that treat diabetes and cardiovascular disease. Koenig and Edelberg said it is happening on the pharmaceutical side as well, because that’s where patient care is headed.
“We see that convergence—we know that many of the patients who have cardiovascular disease are living with diabetes,” said Koenig. By offering patients a full set of treatments, Edelberg said, “We focus on the whole individual.”