With the American Heart Association’s annual meeting in New Orleans underway this week, there’s been plenty of talk about the prospects of so-called PCSK9 inhibitors, a new class of cholesterol lowering drugs that has struggled to gain traction in the market. Though evidence is being accumulated to prove their worth, the biggest piece of proof—data from large studies showing they can improve health outcomes—will have to wait until next year, according to one of the drugs’ developers, Regeneron Pharmaceuticals.
Tarrytown, NY-based Regeneron (NASDAQ: REGN) and partner Sanofi said this morning that a study called Odyssey Outcomes will continue as planned. The massive, 18,000 patient study is testing whether Regeneron’s PCSK9 blocking drug, alirocumab (Praluent), can reduce not just cholesterol levels but also heart attacks and strokes. According to Regeneron, an independent data monitoring committee completed its latest interim analysis of the data, examining the safety and effectiveness of alirocumab so far, and concluded that the trial shouldn’t be stopped early.
In Odyssey Outcomes, Regeneron enrolled patients who couldn’t control their low-density lipoprotein cholesterol(LDL-C, aka “bad cholesterol”) despite taking statins or other lipid-lowering drugs. These patients had suffered a heart attack or had to be hospitalized due to angina within a year of joining the trial. Patients taking statins were randomized to get either an additional 75 mg dose of alirocumab every two weeks or a placebo. If the cholesterol levels of patients on alirocumab remained high after eight weeks, their dose was bumped up to 150 mg. The data monitoring committee has done interim analyses’ on Regeneron’s trial twice, after a pre-specified number of cardiovascular “events,” including heart attacks or strokes, occurred in the study.
Data monitoring boards can stop trials early for good reasons, like if a drug clearly outperforms a placebo or the drug it’s being compared against. A study can also be stopped early when there’s a clear indication that a drug is ineffective or dangerous. Regeneron’s pre-set bar for stopping Odyssey Outcomes early was if alirocumab lead to a roughly 20 percent reduction in the risk of heart attacks or strokes, and a positive trend towards lowering the risk of heart disease-related death, according to a note to investors from ISI Evercore analyst John Scotti.
Given the many possible reasons the board could’ve had for keeping the trial going, Scotti wrote, it’s “impossible to tell at this stage how it will play out.”
“It’s clear that the effect size [at this stage of the trial] was not large enough to stop the trial early, but [we] would caveat from reading in too much to the end result,” he wrote.
Still, shares of Regeneron fell about 3.5 percent in pre-market trading on Thursday, because billions of dollars are at stake in both this trial and a separate one being run by rival Amgen (NASDAQ: AMGN) on its approved PCSK9-blocking drug, evolocumab (Repatha). Both drugs were approved in 2015 and hailed as a huge medical advance in the treatment of heart disease, a leading cause of death in the U.S. But their high price tags—both cost about $14,000 per patient per year—have led to pushback from insurers and disappointing sales. In their last reported quarters, the two drugs had roughly $80 million in worldwide sales combined. Analysts have predicted multi-billion dollar peak sales totals for each drug.
That’s what makes these outcomes studies so important. Should these drugs prove they can lower the risk of a heart attack, their value, and case to payers, could increase tremendously. Both trials are expected to wrap up next year, with data from Amgen, according to Scotti, possible as early as January.
Still, some are convinced that these drugs will remain niche products regardless of how these trials play out because of their price.
“Even if the outcomes studies are positive [these drugs are] still going to cost $14,000 a year,” Kausik Ray, a professor at Imperial College London (and who, it should be noted, is an investigator in trials for a rival experimental PCSK9-blocking drug from Medicines Co. and Alnylam Pharmaceuticals), said to Xconomy earlier this week. “The prices should come down because at the current rate, people are not going to be able to afford them.”
Photo courtesy of Flickr user photosteve101 under a Creative Commons license.