Coming Soon: Lower Cholesterol From a Twice-a-Year Shot?
TUESDAY, Nov. 15, 2016 -- Instead of popping a pill every day, people might soon control "bad" LDL cholesterol by getting an injection at their doctor's office two or three times a year.
Researchers testing a new injectable drug called Inclisiran found it cut LDL cholesterol by half or more. According to early clinical trial data, the effect could last for four to six months.
Inclisiran produced "significant and durable reductions in LDL cholesterol, and thus could potentially impact cardiovascular events," said study presenter Dr. Kausik Ray, a professor of public health at Imperial College London in England.
Such long-lasting effects could provide a major advance in preventing heart disease, heart attack and stroke, by helping reduce hardening of the arteries, the researchers said.
The trial results were presented Tuesday at the American Heart Association annual meeting in New Orleans. Another phase of research is needed before Inclisiran can receive U.S. Food and Drug Administration approval.
However, another clinical trial presented at Tuesday's meeting showed that combining statins with Inclisiran's class of cholesterol-lowering drugs -- PCSK9 inhibitors -- can help drive LDL cholesterol levels down to previously unseen levels.
When paired with a statin, a PCSK9 inhibitor called Repatha (evolocumab) reduced LDL cholesterol levels by nearly 60 percent more than statins alone, said lead researcher Dr. Steven Nissen. He's chair of cardiovascular medicine at the Cleveland Clinic in Ohio.
Ultrasound scans showed that bringing cholesterol levels that low prompted hardening of the arteries to reverse in four out of five patients, Nissen said.
The Repatha study involved 846 patients with coronary artery disease. Half received statins alone, and others received the PCSK9 inhibitor and statins.
About 81 percent of patients taking Repatha and statins showed a reduction in arterial plaque volume, the results showed.
"We have never seen levels of regression at that magnitude in any study previously," Nissen said. "It's really quite extraordinary."
Nissen's study results were also published online Nov. 15 in the Journal of the American Medical Association.
Drugs such as Repatha and Inclisiran spur the liver to flush more LDL cholesterol out of the bloodstream by blocking a protein called PCSK9.
Unfortunately, first-generation PCSK9 inhibitors like Repatha require patients to receive 12 to 24 injections a year, making them inconvenient and expensive, Ray said.
Inclisiran is a next-level PCSK9 inhibitor, which works on a genetic level to prevent cells from producing PCSK9 in the first place, Ray said.
The Inclisiran clinical trial involved 500 people who were assigned to either a "control" group or one of four groups that received different doses of the drug.
One dose of Inclisiran at 300 milligrams or greater caused a 51 percent drop in LDL cholesterol that lasted at least 90 days, while two doses caused a 57 percent reduction that lasted up to six months, Ray reported.
Based on these results, Ray and his colleagues estimate patients would only need an Inclisiran injection two or three times a year to control their cholesterol.
However, Dr. Borge Nordestgaard noted that these are early results.
"The key question is, will the LDL cholesterol reduction, which is very impressive, be sustainable over time," said Nordestgaard, a clinical professor with Herlev-Gentofte Hospital in Herlev, Denmark.
There are similar questions regarding the reduction of arterial plaque related to PCSK9 inhibitors, said Dr. Robert Eckel, a professor of cardiology at the University of Colorado Anschutz Medical Campus.
While drastically lowering LDL cholesterol does reduce arterial plaques, Eckel said he is waiting for the clinical trials to show whether this will actually reduce heart attacks and strokes in these patients.
If the remaining arterial plaques are softer and less dense, they might actually pose an increased risk because they are more likely to break free and block an artery, Eckel explained.
"We have to wait to see if this will impact patient outcomes," Eckel said.
Both clinical trials showed side effects from the drugs similar to those reported by people taking either statins or placebos, the researchers reported. Muscle aches, headache, fatigue, back pain, high blood pressure, diarrhea and dizziness were the most common side effects.
Both trials are funded by the drug's manufacturers, The Medicines Company for Inclisiran and Amgen Inc. for Repatha.
Data and conclusions presented at meetings should be considered preliminary until published in a peer-reviewed medical journal.
For more on PCSK9 inhibitors, visit Harvard Medical School.
Posted: November 2016