The latest cholesterol-lowering drugs rank pretty high on the list of disappointing market launches in recent years. Investors predicted PCSK9 inhibitors could be blockbusters, but they've yet to gain favor with payers due to hefty price tags.
But with a huge potential market, big pharma companies keep trying.
To address cost concerns of insurers and pharmacy benefit managers, Amgen Inc., Sanofi SA and Regeneron Pharmaceuticals Inc. have turned to real-world evidence to tout the benefits of their respective PCSK9 products, Repatha (evolocumab) and Praluent (alirocumab).
The journal JAMA Cardio published results last year from an Amgen-sponsored study of Repatha's cost-effectiveness, in part using real-world cardiovascular outcomes data. The three drugmakers have also inked value-based pricing deals with Cigna Corp. for their meds. As of 2017, Repatha and Praluent's annual costs were around $14,000, significantly higher than the statin therapies many physicians prescribe.
Despite those moves, the treatments still report lackluster sales. The dilemma illustrates that while real-world evidence can shed light on how pharmaceuticals work outside the confines of the clinic, they aren't a sure-fire way to boost a drug's profile — or uptake.
And there are risks. If findings are negative, they could end up hurting product sales or raise new safety signals. And even when outcomes are rosier, real-world data require a great deal of resources to collect, and often leave researchers with more questions than answers.
Where's the data?
Real-world data come in many forms. Patient charts from hospital visits, claims and billing statements from insurance companies, and information from mobile phones or in-home usage testing all fit the bill.
Mining that data can offer valuable insight about patients, like what regimens click best or how certain groups respond to treatment.
"Labels are fairly broad, so we want to find out whether there are specific subgroups of patients that may benefit the most — or the least, quite frankly," Rachele Berria, head of U.S. Diabetes Medical at Sanofi SA, told BioPharma Dive.
Yet, like the rising tower in a game of Jenga, pieces of data are likely to fall astray as the pile of records grows taller.
"In each and every one of the steps there are data missing, information you don't have," Berria said.
The FDA in August issued guidance on the role of real-world evidence in regulatory decisions for medical devices, ultimately concluding that such data, so long as they were pertinent, could be used in those decisions. It's clear the agency is still ironing out its position for drugs, though, complicating matters for manufacturers looking to apply real-world evidence to their products.
"[I]s 'real-world' blood pressure data gathered from an individual’s personal device or health app better (e.g., more reliable and accurate) than a blood pressure measurement from a doctor’s office? It could be," wrote former FDA head Robert Califf and current FDA Principal Deputy Commissioner Rachel Sherman in a Dec. 2015 agency blog post.
"But at the same time, do we know enough about the data gathered from the patient’s personal device — how accurate is it? Is the patient taking their own blood pressure correctly? What other factors might be affecting it? —to use it for generating evidence? Already we are being reminded of the complexities of potentially relying on data that were gathered for purposes other than the ones for which they were originally intended," they wrote.
In the meantime, companies have tinkered with real-world data and the strategies surrounding its use.
Sanofi, for example, has published an analysis of electronic medical records detailing the efficacy, safety, hypoglycemia reduction and healthcare cost utilization for its diabetes medication Toujeo (insulin glargine). The French pharma has also worked on randomized pragmatic trials, a type of clinical study that allows for input from health systems, healthcare professionals and patients.
A payout isn't promised
While negative findings from real-world evidence could prompt the FDA to reconsider a drug's approval, researchers note such an outcome isn't very likely.
"Certainly there are post-approval safety studies that are kind of more real-world evidence that could somehow uncover or magnify a safety signal that we weren't aware of or we didn't appreciate," Todd Hobbs, chief medical officer of North America at Novo Nordisk A/S, told BioPharma Dive. "But by the time that we run the clinical trials and are through the phases and get approval, we've really explored a great deal of safety data that we feel obviously very comfortable with."
Rather, real-world evidence is most frequently used to determine whether a drug performs better to rival therapies or is worth coverage from payers.
Diabetes drugmakers like Sanofi and Novo, pinched by pricing pressures and negotiating power from PBMs, know all too well just how important that data is. In the third quarter, Sanofi watched sales for its blockbuster Lantus (insulin glargine) fall 15% year over year, largely because of formulary exclusions.
"The cost-effectiveness element and finding out what makes [treatments] appropriate for that specific patient that we want to help, that's the big payout," Sanofi's Berria said. "It's also what the payers are looking into more and more."
Amid lower Lantus sales, Sanofi has set its sights on proving Toujeo is a formidable follow-on product. Last June, the company touted real-world evidence from a study showing at-risk, older adults with Type 2 diabetes were at significantly less risk of developing hypoglycemia with similar blood sugar control after switching to Toujeo versus another basal insulin, including Lantus, Novo's Levemir (insulin detemir) and Novo's Tresiba (insulin degludec).
The evidence hasn't exactly solved Sanofi's woes, though. U.S. third quarter sales of Toujeo were down 6.6% to €108 (about $134 million) compared to the same period in 2016. The company's overall diabetes business fell 10% in the quarter.
Sanofi and many other biopharmas remain invested in the potential of real-world data, despite the muted clout the information has garnered thus far. A recent Deloitte survey of life sciences companies found more than half intended to pump more money into expanding the capacity of their real-world programs.
"Whether approved already products or one that's in development, it's going to continue to rise in importance," Hobbs said of real-world data. "The days of just having the clinical trial data, and then you're able to go forth and be used out there in the free market without the worries of long-term [outcomes], that's gone."