From Concept to Clearance: Why It’s So Expensive to Develop New CV Drugs

It costs tens of millions of dollars to approve any new therapy for clinical use, but a recent analysis found cardiovascular drugs can come at a price more than 100-fold higher than the average (JAMA Intern Med 2018;178[11]:1451-7).

Thomas J. Moore, a senior scientist at the Institute for Safe Medication Practices, and colleagues studied FDA Center for Drug Evaluation and Research reports, ClinicalTrials.gov, FDA reviews and peer-reviewed publications to determine how much money sponsors need to spend to prove a therapy is effective. They found the average clinical trial needed for a drug to earn FDA approval costs $19 million.

The researchers identified 59 novel therapeutic drugs studied in 138 pivotal clinical trials conducted between 2015 and 2016. Estimated costs of trials ranged from under $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 a heart drug.

Moore says a handful of factors make the biggest contributions to trial costs: the numbers of patients and sites, and the trial length.

“Drugs are more expensive to test when they have smaller effects that require observing more patients for longer periods of time,” he told CardiovascularBusiness.com. “This applies to many cardiovascular drugs because they have to be shown noninferior 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 was linked to existing therapies, driving the cost upward. The trial tested a novel sacubitril-valsartan combination drug for heart failure against enalapril. Edoxaban trials took a similar effort, costing $174.3 million to prove the drug’s clinical benefit over heparin and warfarin.

Cost of complexity 

Cardiovascular drug development hasn’t always such been a pricey process. In 2014, an analysis commissioned by the Department of Health & Human Services  (HHS) found the costliest phase III clinical trials were in pain and anesthesia, with an average $52.9 million price tag. Ophthalmology studies ranked second ($30.7 million), 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 to dermatology’s $8.9 million). So why, in 2019, is it a struggle to afford new therapies?

Moore says it’s the kinds of drugs being developed that are raising costs the most. “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 explains. 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 for the sacubitril-valsartan trial is a sliver of the total cost to develop and market the treatment. It's unclear how those dollars affect the eventual prices of heart drugs, which some patients struggle 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 says. “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 says it is 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,” he says, “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.”