With FDA OK, Amgen’s Heart Drug Faces Rival (And Health Budgets)

Xconomy National — 

[Updated and corrected 8/27/15, 7:28pm, see below.] The new race to fight cholesterol is on. For the second time in a month, the U.S. Food and Drug Administration has approved a drug for people with dangerous levels of cholesterol who aren’t getting enough help from statins, which have long been among the world’s most prescribed medicines.

The agency said Thursday that doctors can prescribe evolocumab (Repatha), made by Thousand Oaks, CA-based Amgen (NASDAQ: AMGN), for certain people whose high cholesterol is not being lowered enough by statins and a change in diet.

Just as it did one month ago for a similar drug, alirocumab (Praluent), the FDA has given doctors a wide berth to decide which patients among potentially millions are eligible for the drug. In its press release this afternoon, the FDA said evolocumab could be used in patients who have inherited a condition that gives them dangerously high levels of cholesterol, as well as in patients with a history of heart disease who aren’t being helped enough by statins.

[This paragraph updated to include payment language and Amgen comments.] Amgen has set an annual price of $14,100. But it also said in a press release that the net price of evolocumab would be linked to cholesterol reductions and “anticipated appropriate patient utilization.” Amgen officials did not hold a conference call to discuss the news. When asked whether the language meant Amgen would be paid on a sliding scale based on how well evolocumab worked, or how well patients stayed with their injection schedule, a spokeswoman said the company had no comment beyond what was in the press release. She also declined to say when more details would be available.

When alirocumab gained approval in July, its owners Regeneron Pharmaceuticals (NASDAQ: REGN) of Tarrytown, NY, and France’s Sanofi (NYSE: SNY), announced it would cost slightly more, about $14,500 a year. Patients are meant to self-inject the drugs every two weeks for life. (Evolocumab will also have a monthly option, due out next year.)

Both approvals—and the leeway doctors seem to have to prescribe the drugs—are almost certain to generate pushback from insurance companies and their drug-buying middlemen, who have issued dire warnings about the costs of alirocumab and evolocumab if widely prescribed.

European regulators approved evolocumab in July and are likely to approve alirocumab, as well.

The competition between alirocumab and evolocumab began well before the approvals. In 2014, Regeneron and Sanofi paid $67.5 million in 2014 for a voucher that let them speed up the FDA review of alirocumab by a few months, which is why their approval date arrived one month before Amgen.

Both drugs block a protein known as PCSK9 (proprotein convertase subtilisin/kexin Type 9), that makes it harder for the body to get rid of the bad form of cholesterol, LDL-c. By blocking PCSK9, alirocumab and evolocumab help the liver do its job to flush LDL-c out of our arteries. Both are monoclonal antibodies.

Another PCSK9 inhibitor antibody, from Pfizer, is in Phase 3 trials. Farther down the road is a an RNA-based drug from Alnylam Pharmaceuticals (NASDAQ: ALNY) that should produce Phase 1 data next weekend at a medical conference in London.

The approval of both PCSK9 drugs is good news first and foremost for people who have inherited hypercholesterolemia, a dangerously high level of cholesterol. The so-called homozygous form, often known by the shorthand HoFH, is rare and severe; children with it can die of heart attacks. It afflicts anywhere from 1 in 160,000 to 1 in 1 million people worldwide, according to the FH Foundation. Those people will prime candidates for PCSK9 drugs. They are specifically noted on the FDA’s label for evolocumab, but not on the label for alirocumab, because Regeneron and Sanofi did not test their drug in that population. (If doctors adhere to the label, that puts alirocumab out of reach for the estimated 2,000 people in the U.S. with HoFH.)

[A previous version of this story misstated the U.S. HoFH number.]

The FDA approved both drugs for people with heterozygous hypercholesterolemia, or HeFH, which is inherited from only one parent. One in 200 to 500 people worldwide have HeFH, according to the FH Foundation.

But they could end up in a gray area from an insurer’s point of view, says FH Foundation president Katherine Wilemon, who herself has HeFH—and had a heart attack at age 39.

Insurers might want doctors to exhaust all other possibilities, including more statins, before paying for the new drugs. Wilemon said her foundation is collecting data on denials of coverage for alirocumab that insurers have already begun to issue to people with FH.

People who have stubbornly high cholesterol for other reasons, such as statin intolerance, might also have trouble getting coverage. Insurers have said they will want hard evidence of intolerance before paying for a switch to costlier medicine.

Discussing the alirocumab approval last month, Regeneron officials were circumspect about the potential pool of patients that might receive their drug. Regeneron’s top commercial executive Bob Terifay said 8 to 10 million people potentially fall under the populations described by the FDA—“people who are on statins but not ‘at goal’”—in other words, they’re not at the cholesterol levels their doctors have deemed healthy.

But Terifay added that alirocumab would only be prescribed for people who have reached a maximum dose on statins yet still need to lower cholesterol. Terifay said Regeneron would have an “education program” to make sure that people taking statins are up to their maximum dose. Such a program could “limit the patient population eligible for PCSK9 inhibitors,” he said.

The link between PCSK9 drugs and better health is only indirect. In clinical trials, they’ve shown to be effective at lowering cholesterol—which is good enough for FDA approval—but it will take longer-term studies to show that they lead to fewer heart attacks, strokes, and deaths. Such studies are ongoing, run by Amgen, Sanofi/Regeneron, and Pfizer, and should produce data in 2017 and 2018.

The approval was announced after market close Thursday. Amgen shares were up $1.74, just over 1 percent, in after-hours trading. Regeneron shares were up $2.53, about half a percent, and Sanofi was up 95 cents, nearly two percent.