Amgen's Repatha wins in outcomes trial, but is the score high enough?

Repatha pack and injector
Amgen's new Repatha data show PCSK9 drugs beat statins alone at cutting CV risks, but "we do not know the full benefit and thus cannot predict if and when any payers will open up access to the class,” Barclays analysts said Friday.

It’s official: Amgen’s cholesterol-fighting PCSK9 drug Repatha cut cardiovascular risks in an outcomes trial. The drug hit its primary and secondary goals in that study, dubbed Fourier, the company said Thursday.

But that’s all it said. And with detailed data awaiting presentation next month at the American College of Cardiology meeting, the release understandably left most questions unanswered, including the most important question: Will the new outcomes data be enough to persuade insurers and pharmacy benefits managers to open their pocketbooks and routinely pay for the drug?

“Today’s results indicate that while PCSK9 inhibitors offer an improvement over statins, we do not know the full benefit and thus cannot predict if and when any payers will open up access to the class,” Barclays analyst Geoff Meacham said in a Friday note.

Pharma watchers had generally expected Repatha to succeed in the trial, given PCSK9 drugs’ ability to dramatically lower LDL cholesterol levels. Previous clinical trials have shown that lowering LDL levels can lower heart risks, as seen in studies of statin meds, the current standard therapy, and Merck & Co.’s Zetia, a cholesterol fighter that works in a different way.

The big question for Repatha—and for PCSK9 drugs in general, including Sanofi and Regeneron’s Praluent, the only other drug in the class now on the market—is the size of that risk reduction. Payers, physicians and analysts have said that, with list prices north of $14,000, the two meds need to cut risks by a hefty margin—20% is an oft-quoted number, though others think the threshold is much higher—to gain strong insurance coverage and broad adoption among prescribers.

Repatha and Praluent can’t boast of either right now. Since the two meds were approved virtually at the same time in October 2015, payers have raised prior authorization hurdles to limit use of the PCSK9 class, blunting their launches. Further complicating matters, some top cardiologists limited their own prescribing, saying they’d wait for more evidence that the drugs could actually cut heart risks in addition to reducing cholesterol.

For two meds that had been vaunted as certain blockbusters, those setbacks were big disappointments—and the outcomes trials underway have been even more hotly anticipated because of them.

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Right now, what we know is that Repatha “significantly reduced the risk of cardiovascular events” in patients with clinically evident atherosclerotic CV disease, compared with statin therapy alone, as Amgen noted in its Thursday release. The drug hit its primary goal of reducing the risk of a composite endpoint, composed of CV death, nonfatal heart attack, nonfatal stroke and coronary revascularization, aka bypass surgery. It also hit the “key secondary composite endpoint,” Amgen said, which comprised CV death, nonfatal heart attack and nonfatal stroke.

Repatha has delivered some outcomes data before; in Amgen’s Glagov study, the drug reduced plaque buildup in the arteries better than intensive statin therapy alone, as measured with high-resolution imaging technology. Nearly two-thirds of the patients in the trial saw a reduction in plaque burden, Amgen R&D chief Sean Harper said at the time.

Also at the time, Harper scolded payers for dragging their feet on coverage. Now, he says he’s looking forward to rolling out the Fourier data at the ACC meeting. The study results “show unequivocally the connection between lowering LDL cholesterol with Repatha and cardiovascular risk reduction, even in a population already treated with optimized statin therapy," Harper said in Thursday’s statement.

Will those numbers be enough to sway payers? Meacham said his firm expects a 20% reduction, and at least that much would be necessary to win broad coverage—with 25% “ideal” but unlikely, he wrote. Leerink Partners think the number is higher. To make a big difference with doctors and insurers—and to really boost adoption of the PCSK9 drugs—they’ll need to see "substantial benefit in the outcomes trials, including overall survival," Leerink’s Geoff Porges told investors earlier this year. "[C]loser to 50% than 25%,” he said.

Of course, Sanofi and Regeneron’s Praluent doesn’t just need to deliver its own outcomes data, which are due to begin rolling in later this year, Sanofi said on Thursday. They’re in a pitched battle to defend their drug in a patent fight with Amgen—one that could force Praluent off the market as soon as next month. Sanofi and Regeneron have appealed a district-level court decision in Amgen’s favor.