In a tale of two studies, health researchers report that Amgen Inc.’s cholesterol medication Repatha reduces the risk of heart disease, while another study finds that insurers balk at paying the steep price for the first-in-its-class drug. Thousand Oaks-based Amgen’s Repatha is one of a new class of pharmaceuticals called PCSK9 inhibitors that work by reducing LDL or “bad” cholesterol by binding to the PCSK9 protein, which is responsible for regulating the liver receptor that clears cholesterol. Since hitting the market in August 2015, Repatha’s adoption rate has been off to a slow start as insurers are reluctant to pay the lifelong medication’s $14,500 annual price tag and physicians are hesitant to prescribe a pioneering drug lacking long-term data. Last month the Institute for Patient Access released its Health Plan Coverage Report Card, where it analyzed reimbursement rates by different insurers for PCSK9 inhibitors. The physician-led policy research organization is funded by many of the major drug companies, including Amgen and Regeneron Pharmaceuticals Inc., which in partnership with Sanofi, makes Praluent, the only other PCSK9 drug on the market. The report concluded that insurance companies rejected requests for PCSK9 medications an average 39 percent of the time in California from mid-2015 to mid-2016. Federal Employee Benefit Plan and Blue Shield of California topped the thumbs-down list, rejecting 84 and 66 percent of PCSK9 inhibitor claims respectively. Molly Weedn, Blue Shield’s senior manager of corporate communications, could not confirm the study’s results, stating in an email to the Business Journal that it was “unclear” where the data used was derived from. She also discussed Blue Shield’s determination process for PCSK9 inhibitor claims. “In our experience, we’ve found some requests for PCSK9s either do not meet medical necessity because the requested use is not consistent with the FDA approved label or there is not enough information to make a determination initially,” she wrote. “We’re always monitoring medical literature and if new evidence supports expanded use of currently approved drugs, we evaluate our criteria supported by that evidence.” Positive data About the same time as the Institute for Patient Access’ report, a new clinical trial, known as Fourier, examined 27,564 patients at risk of heart attack or stroke, who were already taking optimal doses of standard statin cholesterol medications, like Lipitor from Pfizer Inc. or Crestor from Shionogi & Co. Ltd. On top of their statin treatments, half of the group received Repatha injections, while the other half were given placebos. “These Fourier 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,” Dr. Sean Harper, Amgen’s executive vice president, said in a statement. Amgen did not respond to a request for comment. The trial found that adding Repatha to statin therapy resulted in a 20 percent reduction in suffering from a heart attack or stroke or dying from heart disease. When accounting for those events and adding the possibility of hospitalization due to chest pain or stent implantation to open a blocked artery, the study found a 15 percent reduction in Repatha users. However, Fourier found “no observed effect” on cardiovascular death rate, which could arguably change over time as this study was limited to two years. Amgen analyst Eric Schmidt of Cowen & Co. said Repatha’s upside gives the drug blockbuster potential in the future. “This is excellent news,” he explained in an email to the Business Journal. “Many physicians and payers had been withholding use of Repatha pending proof that the drug not only lowered cholesterol but also lowered cardiovascular disease risk. This data opens up the possibility of much more widespread physician prescribing and greater access in terms of reimbursement.” In his March 17 report, Schmidt projected Repatha revenue in 2017 to hit $400 million, reaching $1.9 billion annually by 2021. He also estimated that each incremental increase of $100 million in Repatha revenue translates to approximately 5 cents earnings per share for Amgen shareholders. Last year, the drug generated $141 million in sales, according to the company’s 2016 full-year financial results. Third-party logic Dr. Tien Ng, an associate professor of clinical pharmacy at USC, said for revenue to rise, insurers must pick up the bill. “If third-party payers don’t ever get on board, the drug company knows the drug won’t have a large market share,” he explained. “The biggest barriers are PCSK9 inhibitors are expensive and we currently don’t have enough data on their effect on long-term outcomes. If the data was more comprehensive, more people could potentially require the drugs, and then the drug companies could recoup their investment in drug development even while lowering drug acquisition cost. We haven’t had rigorous outcome data until now, and even now, we need more data to understand the magnitude of benefit in different people and over a longer period of time.” Even with this new study, Ng said insurers may still need more information to prove cost effectiveness, meaning to justify reimbursement, the medication’s impact must outweigh its price. For example, based on this new data, 74 patients would have to be treated for two years to prevent one heart attack, stroke or death caused by heart disease, he said. Thus, the cost to prevent one major adverse cardiovascular event would be north of $2 million, or 74 patients multiplied by $14,500 multiplied by two years. Dr. Seth Baum, who sits on the scientific advisory boards of Amgen, Regeneron and Sanofi and is a member of the cardiovascular disease working group for the Alliance for Patient Access, the Institute’s affiliate member organization, said if a drug is on an insurer’s formulary, then the company has already agreed to the price and should provide it if prescribed. “Unfortunately, although we have a good deal of evidence that many of the patients meet the requirements that the FDA designated in the PI (prescribing information), they are still being denied drugs,” he said. “The PCSK9 rejection process is unprecedented; we’ve never seen this before. It (the PCSK9 inhibitor) represents the single greatest advance in lipid-lowering therapy in three decades, so you don’t want pushback like this for a great therapeutic.” Patent battle The potential for the drug is not lost on Amgen as the biotech has been engaged in an ongoing patent war with New York-based Regeneron and French pharma Sanofi over their competing drug Praluent, which hit the market one month before Repatha. However, Amgen was first to file its patents, which cover the antibodies that inhibit the PCSK9 gene, and is now claiming infringement. The company filed suit in October 2014, and earlier this year, the U.S. District Court in Delaware granted Amgen a permanent injunction, prohibiting the other companies from selling Praluent. The U.S. Court of Appeals suspended that injunction until the companies’ appeal is heard. “This decision is important for patients in the U.S. who will continue to have access to Praluent during the appeal process, giving them a choice in PCSK9 inhibitor treatments to best meet their individual needs,” Karen Linehan, Sanofi’s executive vice president and general counsel, said in a statement. If Regeneron and Sanofi’s motion to suspend proceedings was denied, it could have ceased Praluent sales for up to 12 years until Amgen’s two patents expire in 2028. Depending on the final decision, the lawsuit could give Amgen absolute market share, at least until another PCSK9 pharmaceutical becomes commercially available, or could require Regeneron and Sanofi to pay Amgen royalties to keep Praluent on the market to preserve patient choice. But for now, Repatha remains an expensive medication in the midst of litigation. As a practical matter, if insurance companies routinely deny coverage for a drug, then the benefits of controlling the patents are limited. USC’s Ng said if future data for PCSK9 inhibitors continues in a positive direction, like in the case of the Fourier study, that will force guidelines and experts to better determine how the therapy should be used. That, in turn, will put more pressure on the drug makers to bring down the price for humanitarian reasons as well as pressure insurers to pay for the treatment under the same reasoning. In addition, if more pharmaceutical companies have success with drugs targeting the PCSK9 protein, the increase in competition could also drive down price. “As a clinical practitioner, I think this drug class works, and it’s going to have a niche,” he said. “Patients will benefit, but we have to find common ground on pricing and making the drug more accessible to a broader range of patients.”
