Sanofi and Regeneron Pharmaceuticals Inc.’s cholesterol drug cut levels of the heart disease-causing fat in four studies, and there are early indications it may prevent death and heart attack.
In the largest of the four trials, among 2,341 patients, those receiving the drug, alirocumab, had a 62 percent reduction in their levels of bad cholesterol after six months of treatment compared with those who received a placebo, the two companies said in a statement today. An analysis also showed patients taking the drug had half the risk of early death, heart attack, stroke or hospitalization as the placebo group, though a larger study is needed to confirm that result.
Sanofi is racing Amgen Inc. to be first to market with a new class of medicines called PCSK9 inhibitors that are designed to mimic a rare genetic condition in which people naturally have low cholesterol. Amgen, based in Thousand Oaks, California, said this week it had submitted its product for approval in the U.S., while Sanofi said today it plans to do so this year. The Paris-based company will use a voucher to obtain a priority review by the Food and Drug Administration.
“We don’t like to be number two; we want to be number one,” Elias Zerhouni, Sanofi’s head of research and development, said in a telephone interview.
Sales of alirocumab may reach 1 billion euros ($1.3 billion) by 2020, according to the average of five analyst estimates compiled by Bloomberg.
Trials of Amgen’s drug, evolocumab, showed it cut levels of bad cholesterol by 55 percent to 66 percent. Pfizer Inc., Roche Holding AG, Merck & Co., Eli Lilly & Co., and Alnylam Pharmaceuticals Inc. are also developing PCSK9 inhibitors.
The drugs are being developed for patients who can’t take or aren’t helped enough by statins, a class of cholesterol-lowering medicines that includes Pfizer’s Lipitor and AstraZeneca Plc’s Crestor. About 12 million people in the U.S. and 21 million people worldwide don’t achieve the recommended reduction in LDL cholesterol with statins, according to a Sanofi presentation last year.
Heart disease and stroke are the two biggest causes of death worldwide, accounting for about 25 percent of deaths in 2012, according to the Geneva-based World Health Organization. The low-density lipoprotein, or LDL, form of cholesterol raises the risk of the two illnesses by clogging arteries.
The Sanofi and Amgen medicines lower LDL cholesterol by blocking the PCSK9 enzyme. When left unchecked, the enzyme prevents liver cells from processing LDL cholesterol, leading to higher levels of the fat in blood.
Sanofi and Regeneron said a month ago that alirocumab had met the main goal of nine trials, without providing further data. The two companies presented results from four of the studies at the European Society of Cardiology meeting in Barcelona today.
In the so-called Odyssey Long Term trial, patients taking alirocumab had a 61 percent reduction in LDL cholesterol after 24 weeks of treatment, compared with a 1 percent increase among patients who got a placebo, equivalent to a 62 percent benefit. After a year of treatment, the reduction was 57 percent in the alirocumab group compared with a 4 percent increase in the placebo group, or a 61 percent benefit.
Among those getting alirocumab, 1.4 percent died of heart disease, had a heart attack or stroke or were hospitalized, compared with 3 percent of those who received a placebo. A larger study called Odyssey Outcomes will provide conclusive evidence for whether the drug cuts the risk of death, even though the FDA has said it won’t require evidence the drugs prevent heart attacks and death before approving them.
“It’s important to see this as a signal, but a landmark signal,” Zerhouni said. “For the first time, we have a second drug which seems to indicate” an outcome benefit, he said.
A second trial called Odyssey Combo II showed the drug cut LDL cholesterol by 51 percent, compared with a 21 percent drop in patients taking Merck & Co.’s Zetia, or a 30 percent benefit.
Two other studies, dubbed Odyssey FH I and FH II, showed a 58 percent and 51 percent benefit, respectively, among patients taking the maximum dose of statins and, in most cases, Zetia as well.
Sanofi won rights to alirocumab as part of an alliance with Tarrytown, New York-based Regeneron, in which it owns a 22 percent stake. Sanofi Chief Executive Officer Chris Viehbacher said last year that increasing the holding to the 30 percent limit allowed under the companies’ partnership agreement “could well make sense.”