Amgen Inc. (AMGN)’s experimental heart drug, designed to imitate the cholesterol-lowering effects of a rare genetic mutation, cut levels of the blood fat by 55 percent to 66 percent in clinical trials.
Three studies of Amgen’s evolocumab, presented today at the American College of Cardiology meeting in Washington, showed the drug’s benefits emerged within weeks of starting therapy and showed no serious safety risks in patients taking the drug for as long as a year. Amgen, based in Thousand Oaks, California, said it could file for U.S. approval by the end of this year.
Amgen’s drug is from a novel class of medicines targeting a protein called PCSK9 that’s associated with high levels of bad LDL cholesterol. At least three drugmakers are testing their own versions. The medications are meant to mimic a rare genetic condition in which about 3 percent of people naturally have extremely low cholesterol levels.
“There’s a really nice analogy between what happens in the genetics and what happens with our therapy,” said Scott Wasserman, head of cardiovascular clinical development for Thousand Oaks, California-based Amgen.
About 71 million Americans suffer from high cholesterol, according to the U.S. Centers for Disease Control and Prevention. PCSK9 inhibitors are being aimed at those who can’t tolerate statins or who don’t get their cholesterol under control with older medicines.
About 5 percent of people diagnosed with high cholesterol can’t take statins, and a smaller group -- 1 in 500 -- have inherited very high cholesterol levels. In addition, up to a third of high-risk patients can’t get their cholesterol low enough, even when taking pills such as Merck’s Zetia, AstraZeneca Plc’s Crestor, and generic versions of Pfizer Inc.’s Lipitor, according to a 2009 study in the journal Circulation.
Pfizer, the world’s largest drugmaker, is testing a PCSK9 inhibitor called bococizumab. Sanofi and Regeneron Pharmaceuticals Inc. are working together on another, called alirocumab. Sanofi and Regeneron expect to seek approval early 2015. Pfizer hasn’t said when it plans to seek approval.
Sanofi, Regeneron and Pfizer also released data at the meeting from their own trials. In a final-stage trial, Sanofi and Regeneron’s drug alirocumab cut bad cholesterol levels by 47 percent, compared with 15 percent for Zetia. Pfizer’s drug cut LDL cholesterol by about 52 percent when given every two weeks.
Determining the drugs’ effectiveness in reducing heart attacks and strokes will take years of further study, through what are known as outcomes trials. Pfizer is aiming to have those results as by August 2017, and Amgen, Sanofi and Regeneron by 2018, the companies have said. The U.S. Food and Drug Administration has said it could approve the drugs based on their cholesterol-lowering ability alone.
“The PCSK9 antibodies we’ve seen data for so far are not much differentiated in efficacy and safety, making dosing convenience a potential source of competitive advantage once multiple agents are on the market,” Mark Purcell, an analyst with Barclays Plc, said in a March 27 note to clients.
All of the companies are also working to make sure that their injection devices are easy to use and don’t require large volumes of drug that patients have to inject under the skin.
Amgen is developing two devices to inject the drug -- an “auto-injector” that’s basically a spring loaded syringe, and an automated device about the size of a pager. Patients will peel of an adhesive backing, stick it to their skin and press a button to inject the drugs. After that they can throw it away.
Sanofi is testing an auto-injection pen, as well as a pre-filled syringe. It plans to move both forward in its final trials. Pfizer says it will also have an auto-injector, though wouldn’t say what volume of liquid will be needed.
The Amgen study, dubbed Descartes, in 901 patients with high cholesterol, found a year of monthly injections with evolocumab slashed levels by 57 percent compared to a placebo. The drug offered additional benefits even to those patients who were already getting aggressive therapy. It cut bad cholesterol by an additional 49 percent in patients who were also on a generic version of Pfizer’s Lipitor plus Merck’s Zetia.
In 614 patients with high cholesterol who weren’t getting any treatment, three months of evolocumab slashed LDL cholesterol by 55 percent to 57 percent compared to a placebo. When the drug was compared with Merck’s Zetia, the drop was 38 percent to 40 percent greater, according to the Mendel study published simultaneously in the New England Journal of Medicine.
A third study, called Rutherford, in 329 patients with an inherited condition that causes dangerously high and hard to control cholesterol levels, the drug reduced bad cholesterol by 59 percent to 66 percent. The medicine was given for three months in combination with standard medicines known as statins and other drugs approved to reduce cholesterol levels.
Amgen will release results from two more studies at the meeting tomorrow.
To contact the editors responsible for this story: Reg Gale at firstname.lastname@example.org Angela Zimm