It costs tens of millions of dollars to approve any new therapy for use in a clinical setting, but a recent analysis published in JAMA Internal Medicine found one class of medication comes at a price more than 100-fold higher than the average: cardiovascular drugs.
According to the JAMA study, the average clinical trial needed to push a drug through FDA approval costs $19 million. Lead author Thomas J. Moore, a senior scientist at the Institute for Safe Medication Practices, and colleagues scrutinized reports from the FDA Center for Drug Evaluation and Research, ClinicalTrials.gov, FDA reviews and peer-reviewed publications in an effort to determine just how much money sponsors need to shell out to prove their novel therapy is an effective one.
Moore et al. ultimately identified 59 novel therapeutic drugs represented in 138 pivotal clinical trials between 2015 and 2016, considering dozens of each study’s scientific characteristics. Estimated costs of trials ranged from less than $5 million for studies without a control group for three orphan drugs and less than 15 patients to $346.8 million for a noninferiority trial assessing the clinical benefit of a heart drug.
Moore said there are a handful of factors that contribute most heavily to trial costs, including the number of patients researchers need to recruit to document a drug effect, how many sites are needed around the world and the length of the trial itself.
“Drugs are more expensive to test when they have smaller effects that require observing more patients for longer periods of time,” he told Cardiovascular Business. “This applies to many cardiovascular drugs because they have to be shown non-inferior to drugs we already have, or because they are intended to reduce risk of future events, such as strokes or heart attacks, that may occur rarely. In contrast, an effective new antibiotic could potentially benefit every treated patient in a few weeks’ time.”
The $346.8 million trial Moore and his team identified in their study was indeed linked to existing therapies, driving the cost of the study into the hundreds of millions. The trial tested a novel sacubitril-valsartan combination drug for heart failure (HF) against enalapril, a proven agent in the HF population. Edoxaban trials took a similar effort—it cost researchers $174.3 million to prove the drug’s clinical benefit over two already effective anticoagulants, heparin and warfarin.
Cardiovascular drug development hasn’t always such been a pricey process. In 2014, a large-scale analysis commissioned by HHS found the costliest phase III clinical trials were in the area of pain and anesthesia, with an average $52.9 million price tag. Ophthalmology studies ranked second-most expensive ($30.7 million for phase III trials), while cardiovascular trials ranked third ($25.2 million).
Phase I costs for cardiovascular studies hovered around the therapeutic average, according to the HHS report, and researchers spent the least on cardiovascular trials in phase II ($7 million, second only to dermatology’s $8.9 million). So why, in 2019, are we struggling to afford new therapies?
Moore said it’s the kind of drugs being developed that are raising costs more than anything else.
“The obstacle is that we already have a large portfolio of cardiovascular drugs for many purposes, and some are quite effective, and most now (have) inexpensive generics,” he said. Continuing to develop increasingly complex drugs will only cost more.
And even with further innovation and higher costs for drug development and clinical trials, the $346.8 million it cost sponsors to prove their sacubitril-valsartan combo is just a fragment of the total cost to develop and market the treatment. It's unclear how those dollars affect the eventual prices of heart drugs, many of which patients are currently struggling to afford.
“Our research showed that the typical pivotal clinical trial cost only about $19 million, a small fraction of much higher overall development costs,” Moore said. “We have not studied drug prices, but it is clear that the cost of pivotal trials does not explain the prices charged for some new therapeutic drugs.”
Still, he said it was important the FDA doesn’t lower its expectations for new treatments and continues to require rigorous scientific evidence for new therapies.
“The worst bargain we could possibly make would be to reduce the required testing of new cardiovascular drugs and end up with millions of people paying a lot for a drug that is worse than what we already have,” he said.
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.