The 2019 approval of tafamidis and tafamidis meglumine (Vyndamax and Vyndaqel, Pfizer) was by all accounts a sea change in the treatment of transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM), but its price is provoking outrage.
"Don't misunderstand, I think it does save lives; it's a brilliant development based on amazing scientific observations," Mathew Maurer, MD, principal investigator of the pivotal ATTR-ACT trial that led to the American approvals, told theheart.org | Medscape Cardiology. "But the risk here is patients won't be able to get access to this compound because it actually just costs too much."
Tafamidis meglumine and tafamidis are priced lower than two drugs used to treat polyneuropathy in hereditary ATTR: inotersen (Tegsedi, Akcea) and patisiran (Onpattro, Alnylam).
But with a list price of $225,000 per year, tafamidis is still the "world's most expensive medication for cardiovascular disease," say Maurer, a cardiac amyloidosis expert at Columbia University Irving Medical Center in New York City, and Jerry Gurwitz, MD, a geriatrician from the University of Massachusetts Medical School, Worcester.
The two pull no punches in a commentary published January 8 in JAMA Cardiology, arguing that the "very high prices" charged for tafamidis meglumine and tafamidis "are not justified and appear to be a particularly egregious example of price gouging."
Because ATTR-CM primarily strikes older adults, the cost of the lifelong medication will especially hit patients in the Medicare Part D coverage gap, who are responsible for up to 5% of drug costs. For those who don't receive additional financial support, out-of-pocket costs are about $1000 to $1500 a month, they note.
In a statement to theheart.org | Medscape Cardiology, a Pfizer spokesperson said the price of tafamidis is commensurate with the value that the breakthrough medicine brings to patients and society.
"Ensuring access and affordability is an important priority for us, which is why we have established a number of patient support programs, including a free drug program, to help patients access this medicine," the statement said. "Based on current regulations, we are limited in how we can help Medicare patients reduce their out-of-pocket costs. We believe this is unfair for patients and we are proactively advocating for adding a reasonable out-of-pocket maximum to the Part D benefit."
A Rare or Underappreciated Disease?
The US Food and Drug Administration granted tafamidis orphan drug status, a designation reserved for drugs designed to treat diseases affecting fewer than 200,000 individuals.
Pfizer says ATTR-CM is both rare, with a prevalence of about 100,000 patients in the United States, and significantly underdiagnosed, with a diagnosis rate of about 4% to 5%.
Maurer and Gurwitz agree the true prevalence of ATTR-CM is not known, but point to a recent study showing that wild-type ATTR accounts for 13% of hospitalized patients with heart failure with preserved ejection fraction (HFpEF). Autopsy data also suggest that 25% of 75-year-olds have amyloid deposits in their heart, but that 100% will by age 100.
Given that HFpEF is the most common type of heart failure in older adults, "the actual number of patients eligible for treatment with these agents could reach into the hundreds of thousands," they write.
Targeted screening in high-risk populations, such as African Americans, in whom the Val122lle mutation of the transthyretin gene is common, at one in 25, may also increase the numbers of patients diagnosed.
In the past, patients often didn't live long enough to develop ATTR-CM or did not undergo a heart biopsy previously required for diagnosis. The arrival of a noninvasive diagnostic strategy — coupling technetium-labeled bone scintigraphy with blood testing for monoclonal proteins — has prompted an upsurge in diagnoses, although some physicians are still not using the two tests in tandem as required, Maurer said.
"You can get very wide varying estimates of the prevalence, but I personally don't think this is anywhere near a rare disease given the cases I'm seeing," he said.
Speaking to theheart.org | Medscape Cardiology, fellow author Gurwitz said: "To be honest, even if it is a rare condition, it's going to have substantial implications from the standpoint of cost and healthcare budgets. But if it is not a rare condition and is more prevalent than is understood at this point in time and it [tafamidis] continues to be priced at this level, its impact is going to be almost unfathomable."
Pfizer noted in its statement that although physicians might be more likely to diagnose ATTR-CM now that there is an approved treatment, it remains to be seen at what rate this will continue.
"As part of our commitment to the ATTR-CM community, we intend to conduct two epidemiology studies to help improve our understanding of the prevalence of the disease. If it turns out this is not a rare disease, we will re-evaluate the price accordingly," the statement said.
Both Maurer and Gurwitz say tafamidis should be the standard of care in comparative efficacy trials, but at its current price would add millions of dollars to the cost of such trials. Maurer is a site principal investigator for four phase 3 trials examining patisiran or AGI0 (Eidos Therapeutics) but noted that none are using tafamidis as the active comparator.
One solution may for the Centers for Medicare and Medicaid (CMS) to cover the cost of a tafamidis–placebo arm. There's already a precedent for this in device development, where CMS pays for the standard-of-care pacemaker or left ventricular assist devices in clinical trials of novel devices, Maurer observed.
The authors also argue that although drug makers should be rewarded for innovation, they should also commit to "responsible pricing" of novel therapies. Maurer noted that tafamidis was actually discovered by Jeffery W. Kelly's lab at the Scripps Research Institute, and acquired by Pfizer in 2011 as part of his biotech company, FoldRx Pharmaceuticals.
"I'm supportive of the idea that without their resources, we would never have been able to complete the [ATTR-ACT] trial, and they did bring the drug to market," he said. "I don't want to disavow them of what 'quote-unquote' finances they are entitled to. But whether this price is justified, I think it's not. That's the bottom line."
Although Pfizer won't reveal its internal costs, annual sales of tafamidis could exceed $1 billion, and the cardiomyopathy amyloidosis population is only growing, Maurer said.
"Last I learned from basic business and finance is that when you expand your market, you lower the price," he said. "This drug costs $225,000 in the United States per year as the list price, and it only costs $60,000 a year in Portugal. I don't understand that. There's more patients in the US, but the price has gone up threefold."
Gurwitz reports personal fees and service on the pharmacy and therapeutics committee from United Healthcare. Maurer reports grants, personal fees, and nonfinancial support from Pfizer and Alnylam; grants and personal fees from Eidos and Akcea; and grants from the National Heart, Lung, and Blood Institute and The National Institute on Aging.
JAMA Cardiol. Published online January 8, 2020. Article
Medscape Medical News © 2020
Cite this: Pfizer's $225K Price for Heart Drug Tafamidis Slammed - Medscape - Jan 15, 2020.