Amgen, Regeneron Stocks Go Up As Drugs Bring Cholesterol Down

Ask people at Amgen and Regeneron Pharmaceuticals how they plan to differentiate their powerful cholesterol-lowering drugs from the next guy’s and the answers are a bit muddy.

It hardly matters to investors. Both companies are going to make a bundle in their eyes.

Shares of Thousand Oaks, Calif.-based Amgen rose 5.7 percent today, to close at $163.03, while Tarrytown, New York-based Regeneron climbed 5.2 percent to $451.77. The gains came the first day after investors soaked up data the companies presented over the weekend at the American College of Cardiology meeting in San Diego.

The two biotech companies are both coming down the home stretch with development of targeted antibody drugs made to bind specifically with a protein called PCSK9. This new approach to lowering LDL cholesterol is underpinned by some elegant genetics, and a mounting body of clinical trial evidence that says both drugs can consistently lower LDL cholesterol by 50 to 60 percent and more. That’s lower than generic statins can go, and it’s welcome news for a couple million people who can’t tolerate statins, and for others with genetic abnormalities that give them extremely high cholesterol counts that can’t be adequately controlled by statins.

Both companies are seeking FDA approval for their new medicines, which are both given through injections patients give themselves just under the skin. Both companies are running long-term studies with thousands of patients in an effort to show the drugs are safe with chronic usage.

Regeneron, which is developing its drug alirocumab (Praluent), in collaboration with Sanofi , reported on 18-month follow-up results of their drug in 2,341 patients with high cardiovascular risk. After roughly six months, researchers saw LDL levels drop by 62 percent for those on the drug, compared with those on a placebo. Although the study wasn’t designed to answer the big burning question in cardiology—does that LDL lowering translate into fewer heart attacks, strokes, and cardiovascular deaths over the long haul?—it did offer signs of being on the right track. Regeneron said that 27 of 1,550 patients in the drug group (1.7 percent) suffered heart disease death, heart attack, stroke, or unstable angina requiring hospitalization. That compared with the placebo group, in which 26 of 788 patients had at least one of those major adverse cardiac events (3.3 percent).

Amgen, for its part, had some of its own data along the same lines, published in the New England Journal. The company said its PCSK9 drug, evolocumab (Repatha) plus standard of care treatment reduced adjudicated cardiovascular events, which were defined as death, heart attack, unstable angina requiring hospitalization, coronary revascularization, stroke and transient ischemic attack or heart failure requiring hospitalization. The company reported on two company-sponsored trials that enrolled 4,465 patients, and evaluated their cardiovascular events after one year. Researchers saw adjudicated cardiovascular events pop up 0.95 percent of the time for patients on the Amgen drug, and 2.18 percent of the time for those on the standard of care.

Jay Edelberg, the head of Sanofi’s PCSK9 development and launch unit, noted that his company has developed a 75 milligram low dose, and a 150 milligram high dose, each taken every other week to provide flexibility. The company is also testing a once-monthly injection. “Physicians can choose the dose to get the patient to the target they are aiming for,” Edelberg said.“That type of flexibility is important to physicians treating high-risk patients and to the patients themselves.”

Sanofi estimates there are 11 million people in the U.S., and another 13 million in Europe, who are considered at high risk of cardiovascular disease, who aren’t at their LDL targets.

Amgen’s Scott Wasserman, an executive medical director, said his company is drilling deeply into some of the underlying biology, using sensitive ultrasound technology, to see what’s happening inside blood vessel walls in patients who are seeing such dramatic drops in their LDL scores. Many patients in the studies have long-term histories of plaque buildup in their arteries. “All that atherosclerosis takes times to build up, the hope and thought is that the long-term therapy with these [PCSK9] agents can reverse some of that,” he said.

There is some concern in the medical community that all this cholesterol lowering could be too much of a good thing. Many are asking how low is too low when it comes to LDL cholesterol, and whether there might be a connection to neurocognitive defects.

Regeneron did disclose this risk in its recent 10-K filing, adding that the FDA is keeping an eye out for neurocognitive effects in the PCSK9 drugs. As the company stated:

“The FDA had requested that we and Sanofi make an assessment of potential neurocognitive adverse events across the global development program for Praluent, especially in the longer-term studies. Additionally, the FDA requested that we address the feasibility of incorporating neurocognitive testing into at least a subset of patients in our ODYSSEY OUTCOMES trial or other long-term Phase 3 trial(s). While we have reported, based on analyses conducted to date, that neurocognitive adverse events were generally balanced between treatment groups in our Phase 3 studies, if this or another adverse event signal is detected in future analyses or in subsequent data, the possible approval of Praluent may be delayed or fail, or its commercial value diminished, which could severely harm our future prospects.”

There's another potential risk around pricing, and potential resistance from payers to the prices that Amgen and Regeneron/Sanofi are likely to command for their potent new cholesterol-lowering drugs. But at least today, investors didn’t appear too concerned.