(Bloomberg) — Cardiologist Dan Rader has an unnerving party trick. When he meets people with subtle signs of sky-high cholesterol, he may ask to feel their Achilles tendons. Several times he’s diagnosed a condition that makes them 20 times more likely to die young of a heart attack.
Rader, head of preventive cardiology and human genetics at the University of Pennsylvania in Philadelphia, is looking for fatty buildups in the knees and ankles or white arcs around the cornea of the eye. The hereditary condition he’s seeking, known as familial hypercholesterolemia, affects as many as 1.5 million Americans — a group drug companies see as one of the first markets for a set of potential blockbuster cholesterol drugs.
Diagnosing the patients and their family members won’t only improve their chances for a long and healthy life, it will identify the most robust market for the new drugs. Called PCSK9 inhibitors, analysts estimate the injections will generate more than $2 billion a year each for companies including Amgen Inc., Pfizer Inc., Sanofi and Regeneron Pharmaceuticals Inc.
To capture those sales, drugmakers first need doctors to think like Rader and find the patients.
“Most physicians rarely, if ever, make the diagnosis,” said Rader. “On the patient level, there is virtually no recognition whatsoever. FH is essentially unknown.”
Familial hypercholesterolemia, or FH, increases LDL, or bad, cholesterol levels to as high as 400 milligrams per deciliter, compared with a goal level of 100 milligrams. Already at a greater risk of heart attack and early death, patients also have a 50 percent chance of passing it on to their children.
While there’s a genetic cause of FH, doctors diagnose it based on dramatically high bad cholesterol levels and family history, rather than a DNA test.
Patients are typically treated first with statins, like Pfizer’s Lipitor, though the medicines aren’t usually enough. The PCSK9 drugs are likely to be used at first in patients who can’t take statins, have FH, or who for some other reason can’t get their bad cholesterol levels down.
Karol Watson, co-director of preventive cardiology and director of the Barbra Streisand Women’s Heart Health Program at the University of California, Los Angeles, said she wants hard proof that the PCSK9 inhibitors avert heart attacks before she prescribes them broadly. For the 15 percent of patients she sees with FH, though, she will start recommending them immediately.
Drive it down
“These are individuals with LDL in the 300, 400, 500 range,” she said in an interview. “I have them on four drugs just hoping to get their LDL below 200. We want to drive that down as much as possible.”
A first wave of trials for PCSK9 drugs were designed to show they cut bad cholesterol, which regulators at the U.S. Food and Drug Administration have used as a marker for lowering risk. Along with FH, the drug could be used in patients who can’t take or don’t respond to statins, a population of about 10 million.
Longer trials with thousands of patients are attempting to prove definitively that the PCSK9 drugs reduce risk of heart attacks, stroke and death, which could eventually expand their use into anyone with high cholesterol, a much larger market.
Drugmakers haven’t said how much the injections, which will likely be taken every few weeks or once a month for the rest of patient’s life, will cost. Mark Schoenebaum, an analyst with Evercore ISI, estimates they may charge $4,000 to $5,000 a year.
Taking no chances
The industry isn’t leaving the discovery of the highest-risk patients to chance. At an American Heart Association meeting last month, the companies highlighted the progress made with antibodies to block PCSK9, a protein that interferes with the body’s removal of cholesterol. The medicines can cut cholesterol more than 70 percent and may be the best hope for getting FH patients to healthy levels.
It’s not the first time the industry and medical community has embarked on a campaign to track down an under-diagnosed group. As a new, better generation of treatments for hepatitis C got closer to market, U.S. public health authorities urged people at risk to get screened, identifying thousands of new patients to drugmakers for treatment.