The U.S. Food and Drug Administration has approved the first oral drug of its kind that targets the PCSK9 protein to lower bad cholesterol, in a move that could provide an easier and less expensive option for patients compared to injection treatments.
The new drug, called Lepfindra (Enlistid), works by inhibiting the PCSK9 protein, which limits the body's ability to remove LDL (bad) cholesterol from the blood. It is taken once daily, along with a healthy diet and exercise, to treat adults with high cholesterol, including those with heterozygous familial hypercholesterolemia (HeFH), a genetic disorder that causes high cholesterol levels.
The importance of this treatment stems from the fact that it is an oral alternative to PCSK9 inhibitors, which were previously available in the form of injections. These drugs are effective in lowering cholesterol but can be expensive, with prices ranging between $500 and $600 per month or more, and some patients prefer to avoid injections.
Julie Cunningham, a spokeswoman for Merck, the drug's developer, said that Lepfindra will cost $315 for a 30-day supply and is expected to reach pharmacies within a few weeks.
The FDA approval came after two clinical trials involving 3,207 adults who were already taking the highest dose of statin drugs they could tolerate.
The first study, which included people with or at risk of developing ASCVD, showed that the drug reduced the average level of LDL cholesterol by 56% after 24 weeks compared to a placebo, after the baseline level had been 96 mg/dL.
The second study, which focused on adults with heterozygous familial hypercholesterolemia, showed a 59% reduction in LDL cholesterol levels, which had an average of 119 mg/dL.
Cardiovascular atherosclerosis occurs as a result of the accumulation of plaque inside the blood vessels that supply the heart, and high levels of LDL cholesterol are a major factor that increases the risk of heart attacks and strokes.
The FDA reported that side effects from the drug occurred at rates nearly identical to those from the placebo in one trial, while diarrhea and dizziness were more common among participants taking lepfendra in a trial for patients with heterozygous familial hypercholesterolemia. A similar number of patients in both groups discontinued treatment due to side effects.
Previous data indicates that injectable PCSK9 inhibitors reduce the risk of heart attacks, strokes, and cardiovascular-related deaths by up to 20% in high-risk patients. Merck is currently conducting a clinical trial to determine if Lepvendra offers similar benefits.
Cardiologists welcomed the drug's approval. "I'm very pleased," Dr. Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston, told The New York Times. Dr. David Maron, a preventive cardiologist at Stanford University, added that the drug could represent a significant change compared to the cost of injectable PCSK9 inhibitors.
Dr. Dean Lee, president of Merck Research Laboratories, said the company is seeking to make lowering cholesterol with this drug a routine procedure similar to taking statins, so that primary care physicians can also prescribe it, not just cardiologists.
Recent guidelines from the American Heart Association and the American College of Cardiology recommend lowering LDL cholesterol to less than 70 mg/dL for people at higher risk of heart attacks or strokes, and to less than 55 mg/dL for higher-risk groups, such as heart attack survivors.
