The quest to inhibit the cholesterol-related enzyme PCSK9 has produced two high-profile drugs and a massive patent battle between their makers. Now a group of scientists in Europe, along with the biotech company Affiris, are proposing a different way to inhibit PCSK9—with a vaccine that they say showed promising results in mice.
A study published in the European Heart Journal concludes that it may be possible to immunize people against developing high cholesterol and atherosclerosis, or the narrowing of the arteries, according to a press release. The vaccine, AT04A, consists of a molecule that prompts the body to produce antibodies against the enzyme. Once PCSK9 is inhibited, the body is able to properly clear LDL cholesterol, commonly dubbed the “bad” cholesterol.
When the vaccine was injected in mice that were fed fatty food to induce high cholesterol and atherosclerosis, their total cholesterol fell 53%, according to the release. Damage to blood vessels fell 64%, while blood vessel inflammation decreased by at least 21%, the scientists said.
“As antibody concentrations remained high at the end of the study, it can be assumed they would continue to reduce cholesterol levels for some time afterwards, resulting in a long-lasting effect,” said Günther Staffler, chief technology officer at Affiris, in the release. He added that if those results translate to people, it may be possible to protect against high cholesterol and its impact with an initial vaccination and then an annual booster.
Just how safe such a strategy may be remains to be proven, however, said Ulrich Laufs of Saarland University in Germany and Brian Ference of the University of Bristol, U.K., and the Wayne State University School of Medicine in Detroit, in an accompanying editorial. Existing drugs designed to lower cholesterol have been associated with an increased risk of diabetes, they noted. That’s among the risks that “need to be very carefully addressed during the course of clinical development," they said.
The potential for targeting PCSK9 in people with uncontrollably high cholesterol has not yet been fully realized. When Amgen’s PCSK9 inhibitor Repatha and the rival Sanofi/Regeneron drug Praluent were approved a couple of years back, analysts predicted the total market would hit $3 billion by 2022. But in the first quarter of this year, each drug brought in about $20 million—largely because insurers are balking at their high price tags and making doctors prove their patients really need them.
And just who will dominate the PCSK9 market remains a question that may well be answered in court. Amgen won an injunction against Sanofi and Regeneron in a patent dispute earlier this year, which threatened the removal of Praluent from the market. That’s now on appeal, with the balance of the market prognosticators betting that Amgen will win and have the market to itself.
The folks at Affiris aren’t fazed by the travails of early PCSK9 contenders. They’ve already started a phase 1 trial of AT04A in people. And if the approach proves safe and effective, said Laufs and Ference in their editorial, it could prove more affordable than antibody approaches like Repatha, especially because the vaccine would be given once per year, versus monthly for Amgen’s drug. Therefore, they wrote, “it appears promising to evaluate further the long-term LDL-C lowering by vaccination against PCSK9 for the prevention of atherosclerotic events.”