By AMERICAN HEART ASSOCIATION NEWS

0826-Feature-PCSK9 inhibitors_Blog

A second in a new class of drugs that sharply lowers cholesterol is set for federal approval by Thursday – a “game-changer” for the hardest-to-treat patients who are in danger of heart attacks and strokes.

For people with familial hypercholesterolemia, or FH, a genetic condition that causes very elevated levels of “bad” LDL cholesterol, drugs called PCSK9 inhibitors will be a new hope in preventing premature heart disease, said Daniel J. Rader, M.D., chair of the department of genetics at the Perelman School of Medicine at the University of Pennsylvania.

The U.S. Food and Drug Administration last month approved Praluent (alirocumab) from Sanofi and Regeneron Pharmaceuticals. A second drug, Repatha (evolocumab) from Amgen Inc., is set for a decision by Aug. 27.

Both drugs, given by injection, decrease LDL by targeting the PCSK9 protein that regulates how much LDL the liver can flush from the body. Statins, the current mainstay therapy for high cholesterol, block the liver’s production of LDL cholesterol. High cholesterol can contribute to plaque buildup in arteries that feed the heart, brain and extremities, which can lead to heart disease, blockages and strokes.

Clinical trials have shown that PCSK9 inhibitors can decrease LDL by about 40 percent to 60 percent, whether used alone or with statin drugs. The FDA approved Praluent for use with diet and maximized use of statins in adults with FH or who have cardiovascular disease and require additional substantial lowering of LDL cholesterol.

“It’s quite dramatic,” said Rader, who is also the chief science advisor for the FH Foundation, a nonprofit focused on education, advocacy and research about the condition. “This is the first new LDL-lowering class of drugs approved for a broad segment of the population in over a decade. The value to the individual patient who needs this treatment is huge.”

That’s almost an understatement for Jonathan Karas. He, his wife and their 8-year-old son have FH. For Karas, the condition led to a heart attack at the age of 28. His son has a rarer aggressive form of the condition called homozygous FH.

“This brings hope to families who are dealing with FH,” said Karas, who is now 40. “I believe the more options, the better.”

For now, Karas’s condition is holding steady with a statin and another drug. But he said he feels safer knowing PCSK9 inhibitors could be a possibility in the future for his wife and possibly for his son.

Thousands of FH patients around the world have participated in clinical trials to prove that PCSK9 inhibitors are effective and safe, Rader said. Final results from definitive studies looking at whether the drugs prevent heart attacks and strokes won’t be available until at least 2017.

FH affects an estimated 1.3 million Americans, yet only 10 percent have been diagnosed, according to the FH Foundation. Others who might also benefit from the new drugs are patients who have adverse reactions to statins or for whom the drugs are not effective.

Rader said an important part of the discussion about the possibilities of PCSK9 inhibitors will be just how to determine who needs additional lowering of LDL cholesterol. The newest American Heart Association guidelines on treatment of cholesterol in 2013 showed that the best scientific evidence did not support the setting of specific LDL targets and recommend statin use for all at-risk patients with elevated LDL.

A critical question also will be what criteria insurance companies use in deciding to reimburse for the drugs, Rader said.

The wholesale acquisition price for Praluent on the U.S. market will be nearly $14,000 a year – $1,120 every 28 days for both the 75 mg and 150 mg doses, according to Sanofi-Aventis and Regeneron Pharmaceuticals.

“Now that PCSK9 inhibitors are available, it is a different ballgame with regard to LDL targets,” said Rader, who thinks the AHA guidelines will need to be revised to give doctors and payers more clarity.

“In the current climate, how does a clinician define when LDL is too high and the patient needs a PCSK9 inhibitor?” Rader said. “I’m going to predict there are going to be lots of battles on what constitutes acceptable LDL levels, who needs [these drugs] medically and who is going to pay for them.”

Editor’s Note: The FDA approved Repatha on Aug. 27.