Amgen’s cholesterol-fighter Repatha rolled back atherosclerosis in a new clinical trial, showing that the drug doesn’t just push LDL cholesterol down by impressive margins. But the results might not be enough to give the PCSK9 drug an immediate boost, analysts said.
In the Phase III GLAGOV trial, Repatha showed it could reduce plaque buildup in the coronary arteries better than intensive statin therapy alone, as measured with a high-resolution imaging tool called IVUS. That benefit continued even as “bad” LDL cholesterol levels fell below typical targets, investigators said.
“In fact, nearly two-thirds of patients on Repatha in this trial, the vast majority of whom were already on high to moderate intensity statin therapy at baseline, experienced a reduction in plaque burden,” Amgen R&D chief Dr. Sean Harper said in a statement.
Though the study, presented at the American Heart Association meeting in New Orleans on Tuesday, wasn’t designed to prove cardiovascular benefits such as heart attack prevention, the trend for Repatha patients was positive, Amgen said. The analysis showed that 12.2% of Repatha patients suffered a cardiovascular event, compared with 15.3% in the statin-only group, with a particular trend toward preventing resvascularization procedures, at 10.3% for patients using Repatha and 13.6% in the statin patients.
Doctors and payers have been holding back on using the two PCSK9 drugs now on the market, worried that their payoff for patients isn’t worth the hefty price tags; the list prices on both drugs run $14,000-plus. Repatha, and its head-to-head competitor Praluent from Sanofi and Regeneron, have posted sales that are positively anemic compared with early blockbuster expectations. Pfizer went ad far as to toss aside its PCSK9 development program, despite its hefty investment; it had launched a bococizumab CV outcomes trial even before FDA approval in an effort to set its drug apart.
The new GLAGOV data do bolster Amgen’s case for Repatha by showing an actual clinical benefit in addition to its ability to dramatically lower LDL levels, a surrogate marker for cardiovascular outcomes. And outcomes data are what doctors and payers say they’re looking for to broaden use of the meds.
Evercore ISI analyst John Scotti pointed out the “linear relationship” between LDL levels and the relative size of plaque in the artery—percent atheroma volume, or PAV—the more LDL levels dropped, the more PAV did as well. That trend continued all the way down to LDL levels of 20 mg/dl.
“Notably, all CV events trended favorably,” Scotti wrote in a Tuesday investor note, with the caveat that the trial wasn’t powered to deliver outcomes results.
But as Mizuho Securities analysts pointed out, the change in PAV came in at 1%, slightly below expectations of 2% to 3%. And though the indication of CV benefits was “good in our view,” the real boost for Repatha won’t come until the cardiovascular outcomes trial data appears early next year.
“Bottom line: We have to wait for FOURIER data in first-quarter 2017,” Mizuho analyst Salim Syed wrote in a Tuesday note.
That’s exactly the tune payers, and to some extent doctors, have been singing for months, as the PCSK9 drugs, initially expected to zoom to a blockbuster finish, faltered out of the gate. Amgen has the jump on Sanofi and Regeneron on that score; its outcomes data likely won’t come till 2018.
And there are high expectations for that data, analysts say. 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 Partners told investors earlier this year. What's substantial? "[C]loser to 50% than 25%," Leerink's Geoffrey Porges quoted some payers as saying.
In the meantime, though, Amgen maintains that payers should start covering Repatha sooner rather than later.
“The compelling data from GLAGOV remove any scientific doubt about the ability of Repatha to lower LDL-C and the impact it has on the critical underlying disease process,” Harper noted in Tuesday’s statement. “We remain concerned that many patients are experiencing barriers to accessing Repatha, despite their physician’s treatment recommendations.”