‘Outrageous’ $225,000 per Year List Price for Tafamidis Draws Outcry

Several heart failure physicians, specifically those who treat patients with cardiomyopathy caused by transthyretin amyloidosis (ATTR-CM), are calling attention to the extraordinarily high price of tafamidis and tafamidis meglumine (Vyndamax and Vyndaqel; Pfizer), both of which received orphan drug designation and were approved by the US Food and Drug Administration in 2019.

With a list price of $225,000 per year, tafamidis is the most expensive cardiovascular drug on the market. Mathew Maurer, MD (Columbia University Irving Medical Center, New York, NY), who published his views along with Jerry Gurwitz, MD (University of Massachusetts Medical School, Worcester), January 8, 2020, in JAMA Cardiology, told TCTMD the high prices for tafamidis “are not justified and appear to be a particularly egregious example of price gouging.”  

The out-of-pocket costs for most patients are difficult to pin down given rebates and subsidies, but Maurer said his patients pay roughly $1,000 to $2,000 each month if they don’t receive additional financial support. “It’s anxiety provoking,” he said. “If nobody believes that, come to my clinic where I have to sit with patients who are worried how they’re going to get it, if it’s going to be sustainable, and if it’s going to work out. That’s a shame if you’re sick.”

It’s anxiety provoking. If nobody believes that, come to my clinic where I have to sit with patients who are worried how they’re going to get it. Mathew Maurer

Rodney Falk, MD (Brigham and Women’s Hospital, Boston, MA), who runs a specialized cardiac amyloidosis program, called the list price “outrageous.”

“Almost two-thirds of our patients have an initial monthly copay of more than $1,000 per month with Medicare,” he told TCTMD. “Those with very low incomes—those are people who can usually get some type of subsidy. But for the average person on an average income, $1,000 is still a lot of money and they can’t get any subsidies.”

One patient with ATTR-CM, said Falk, ran the numbers and weighed the financial impact with his current symptoms, and despite his life-threatening, progressive condition ultimately decided against tafamidis. “He went out and bought himself a brand-new pickup truck,” Falk recalled, “because he said that’s the drug cost for the first 2 years and he might as well enjoy himself.”

What Is ATTR-CM?

ATTR-CM is inherited as an autosomal dominant trait caused by mutations in the transthyretin gene (TTR) or by the deposition of wild-type transthyretin proteins. Tafamidis slows the progression of ATTR-CM—it doesn’t cure it—but experts have cautioned that a delayed diagnosis typically leads to worse prognosis. The average life expectancy from the time of diagnosis until death is roughly 2 to 6 years.  

That quarter-of-a-million dollar per year price tag might be justified if ATTR-CM was an extremely rare condition, but experts say that just isn’t the case. To TCTMD, Ronald Witteles, MD (Stanford University Medical Center, CA), who is co-director of the amyloid program at his institution, said he was “surprised, and not happily so” when Pfizer announced the price of tafamidis following the FDA approval.

“It was priced like a drug is typically priced for a truly rare disease, which this simply isn’t,” he said, adding that if there were 1,000 people or fewer in the country with ATTR-CM, the inflated price tag might be expected. “It’s not common like high blood pressure or coronary artery disease, but it is definitely not truly rare.”

Like Maurer and Gurwitz, Witteles pointed out that Medicare Part D patients in the coverage gap can be responsible for up to 5% of the drug costs. “For a drug that’s $1,000 a year that isn’t too big a burden,” he said. “For a drug that’s $225,000 a year, that’s a very different story.”

Maurer said the prevalence of ATTR-CM is not truly known, noting that there are few population-based epidemiological studies documenting the disease. Pfizer estimates the prevalence of ATTR-CM to be approximately 100,000 people in the United States and that approximately 4 to 5% of people are diagnosed, but Maurer and Gurwitz highlight one study suggesting a prevalence of 13% among patients with heart failure with preserved ejection fraction (HFpEF) and increased wall thickness.

It was priced like a drug is typically priced for a truly rare disease, which this simply isn’t. Ronald Witteles

“It’s much more common than we recognized a decade ago,” said Falk. “Every single major amyloid center has seen an enormous surge in TTR amyloid, particularly wild-type TTR amyloidosis. Many people believe it’s responsible for about 5% to 10% of older patients with heart failure with preserved ejection fraction, which is an awful lot of patients.”

In the past, said Maurer, people simply never lived to an age when they’d develop ATTR-CM, a disease that strikes individuals 65 years and older. Also aiding in the increased number of cases is the development of a noninvasive diagnostic strategy, as opposed to a previously required heart biopsy, that uses technetium-labeled bone scintigraphy along with blood testing for monoclonal proteins.

Maurer said that awareness around ATTR-CM is also growing because physicians recognize the deadly nature of the disease. “It’s not an innocent bystander,” he said. “It’s clear that if you find it and treat someone you can help them live longer and feel better, or at least feel less worse.”

In the pivotal ATTR-ACT study, led by Maurer and published in the New England Journal of Medicine, researchers showed that tafamidis reduced the risk of all-cause mortality and cardiovascular hospitalizations at 30 months when compared with placebo . In terms of symptoms, tafamidis treatment led to improvements in the 6-minute walk test and various quality-of-life scores.

To TCTMD, Gurwitz praised Maurer, noting that he’s been on the forefront of research leading to breakthroughs in the diagnosis of ATTR-CM. In their article, the two state that if the prevalence of any disease or condition exceeds 200,000 persons, the orphan drug designation and its market exclusivity should be revisited.

“How would the drug be priced if [ATTR-CM] was a more prevalent condition?” asked Gurwitz. “We don’t know. It could have been priced at the same level, who knows, because pricing isn’t rationale or value-based in any way.”

In a statement, a Pfizer spokesperson told TCTMD the company believes the price of tafamidis is in line with the value the drug brings to patients and society and noted that the list price is not what patients pay. Pfizer also agreed that it’s difficult to measure the true prevalence of ATTR-CM.

“While physicians may 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 in the coming months and years,” the statement reads. “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 reevaluate the price accordingly.”

Subset of the HFpEF Population

Speaking to broader issues, Maurer said researchers have spent 25 years trying to identify the pathophysiology of HFpEF, or diastolic HF. Countless trials testing agents successful in systolic HF have not panned out, but there has been some success in breaking HFpEF patients into different subgroups. ATTR-CM is one of those subgroups, and dedicated research looking only at these patients has led to successful treatment with tafamidis. However, there are a number of other HFpEF subgroups, and if future agents also receive orphan-status designation cost is going to be a major factor.

“How are we going to afford this?” asked Maurer. “If we’re taking what is a common condition and making it into a rare disease because we’ve found a small subgroup, it sounds to me like this is unsustainable. Trust me, I’m thrilled that this drug works. I have hundreds of patients and I’m grateful to give it to them. And I want to be transparent—I think the scientist who developed this, Jeffery Kelly, is brilliant. In my opinion he deserves a Nobel Prize. I don’t even fault the drug company per se. I want them to get their due, but I don’t think we’re considering the societal issues.”

There’s no reason why Pfizer couldn’t swallow the research costs because of the huge profits they’re making off other drugs. Ronald Falk    

Maurer criticized the current system, noting that the US government is unable to set drug prices for Medicare patients and is suffering the consequences for it.

“I think it’s a little bit ludicrous—I love my patients and I think they should get the drug—but to spend a quarter of a million dollars every year on patients who are 80 years of age? Not to be disrespectful to them, but it’s not sustainable,” he stressed.

To TCTMD, Falk said the traditional response from pharmaceutical companies is that the high price is justified given the enormous outlay in research and development.

“I don’t buy that argument,” he said. “There’s no reason why Pfizer couldn’t swallow the research costs because of the huge profits they’re making off other drugs. Secondly, we’ve prescribed it to 100 patients this year. If you reckon $225,000 per year, that’s $22 million that we put into Pfizer. Multiply that by a couple of years, that’s $40 or $50 million and that’s from one center. They’ve made their money back, unquestionably.”     

Moreover, Pfizer isn’t a small company making a single drug. Pharmaceutical companies are frequently touting their commitment to patient care, and this is an opportunity for Pfizer to put their money where their mouth is, Falk said. They could take a loss on tafamidis and earn the money back with drugs for more common conditions.

“They could show themselves to be, I won’t say altruistic, but they could back up what they’re actually saying,” said Falk. “They say, ‘We want to help patients with these [rare] diseases’ and so on and so forth. They could do that.” 

In cardiology, the makers of the PCSK9 inhibitors faced significant backlash when they initially priced alirocumab (Praluent; Sanofi/Regeneron) and evolocumab (Repatha; Amgen) at nearly $15,000 per year, although that drug class is for a much more common disease affecting a significantly larger number of patients. The companies eventually cut their prices—slashing the costs by roughly 60%—when uptake stalled.

“The thinking is, if you lower the price, the drugs will be prescribed more,” said Gurwitz. “Perhaps that might happen here, but I’m not so sure. This isn’t the same scenario.” 

Implications for Research

In addition to the burden for patients and payers, the high cost of tafamidis also has research implications, according to Gurwitz and Maurer. Given the price tag, Pfizer essentially blocks future clinical trials that could use tafamidis as an active comparator, which Maurer said is wrong. Tafamidis is the current gold standard of care in ATTR-CM so future studies should be compared on top of or against tafamidis and not placebo. Maurer is the site principal investigator of several phase III clinical trials about to launch.

“Each one of those trials should, in theory, offer tafamidis to the control group,” Maurer told TCTMD. “That’s what should happen scientifically. That’s important for what I as scientist want to know, as do patients. Is this new drug, when added on top of tafamidis or compared with tafamidis better or worse?”

For that to happen, competing companies would need to buy tafamidis from Pfizer at the list price, which ups the cost of a clinical trial by a couple hundred million dollars depending on its size and duration. “We’re forced to do studies in unideal circumstances,” said Maurer. “And this prevents patients from getting the best drug the fastest.”

As a solution, Maurer believes the US government could get involved by paying for tafamidis in active comparator studies. As part of that deal, they could force companies to keep their prices much lower than Pfizer’s $225,000 price tag if the new drug was successful in clinical testing, he suggested.  

Two agents, inotersen (Tegsedi; Akcea) and patisiran (Onpattro; Alnylam), both of which are approved as orphan agents for the treatment of the much-rarer hereditary amyloidosis, a disease the primarily affects the nervous system, will be tested in patients with ATTR-CM. Patisiran currently has a list price of $350,000 per year, while inotersen costs $450,000. An investigational small molecule (AG10, Eidos Therapeutics) that stabilizes TTR is also being developed for and tested in cardiomyopathy and polyneuropathy. AG10 has already been designated an orphan drug by the FDA.