Sky-high genetic cholesterol primed for blockbuster drug

The market for PCSK9 drugs got another boost last month from a study of a different drug, Merck & Co.’s Zetia, helping calm a debate about cholesterol reduction. A trial of the drug showed that heart risk was reduced when patients got their cholesterol rates even lower than statins could accomplish alone. That bolsters the case for PCSK9s, since it adds to the evidence that FH patients could benefit from cutting cholesterol beyond what statins can do.

Soft sell

Drugmakers also made a softer sell at the heart meeting. There were massive booths offering beverages and educational materials. Sanofi and Regeneron sponsored the meeting’s mobile app, a map of the convention center, and the convention’s hotel room keys had ads touting drugmakers’ PCSK9 research.

Their work is helping identify people who will benefit from a diagnosis and treatment, said Harlan Krumholz, a cardiologist at Yale University in New Haven, Connecticut. There is also the risk that the effort will go too far, he said.

“With FH, there is a hope and a fear,” he said. “My hope is that the many people who have FH who are currently not diagnosed may be identified and counseled and given the opportunity for treatment,” he said in an interview. “But if they overreach and try to expand the market to people for whom the benefits are less clear, they may be doing a disservice.”

Industry sponsors

Patients can also turn to the FH Foundation, the first advocacy organization for the disease. It was created three years ago by Katherine Wilemon, a mother and FH patient from San Marino, California, who struggled to find doctors who understood her condition or other people going through the same thing. The foundation is sponsored by Amgen, Sanofi, Pfizer, Regeneron and other drugmakers, according to its website.

“We are very much supported by the pharmaceutical industry,” said Wilemon, who ran the foundation as a volunteer activity for its first two years and now takes a salary. “That is key in facilitating our efforts. But we are completely independent in how we chose to fulfill our mission.”

It’s not hard for doctors or health care professionals to spot FH once they learn about it. It’s caused by a genetic defect on chromosome 19 that makes it difficult for the body to remove bad cholesterol. Children can have LDL levels greater than 300 milligrams per deciliter, almost 10 times what most people are born with.

Mona Lisa’s disease

Mona Lisa, the woman famously painted by Leonardo da Vinci, is thought to have been a patient. An analysis of the painting found signs of the disease on Mona Lisa’s eye and hand and concluded that she was “probably the first case of familial hypercholesterolemia,” according to a 2008 study in the journal Current Cardiology Reviews.

It’s the less obvious damage — plaque buildup in arteries that nourish the heart and brain — that is most dangerous. Imaging studies can spot the plaque in the carotid arteries leading to the brain in patients as young as 11. By age 50, half of men with the condition have already developed heart disease or died from it, studies show.

Widow-maker artery

Wilemon knew at age 15 that her bad cholesterol topped 300, though she had no idea why. By the time she was 38, Wilemon had suffered a massive heart attack. A key artery, one doctors call the widow-maker, was completely blocked.

“It took two additional years to find a physician who truly understood what I have,” she said. “He suggested I have my daughter checked. She was two. She also has it.”

Since high cholesterol has traditionally been treated the same regardless of the cause — usually with drugs such as Pfizer’s Lipitor, sold now as a generic, or AstraZeneca Plc’s Crestor — there hasn’t been an urgency to find patients. While those drugs alone can’t control cholesterol for most FH patients, they had few other options.

Wilemon’s foundation is sponsoring a patient registry and encourages screening for family members. It’s also trying to get a separate billing code for the condition.

The drugmakers’ effort around the medicines is already having an effect, Yale’s Krumholz said.

“It has been one of the most remarkable educational marketing campaigns of all time,” he said. “We went from not having any understanding of this class of drugs as practitioners, to saying PCSK9 inhibitors off the tops of our tongues. Now I’m fluent.”