Pfizer's ATTR Heart Disease Drug Needs Hefty Discount, Says ICER Draft Report. What About Alnylam's Amvuttra?

Pfizer’s blockbuster drug tafamidis for the treatment of the rare heart disease transthyretin amyloid cardiomyopathy (ATTR-CM) needs at least a 96% discount off its list price to be considered cost-effective under common benchmarks.

The finding came from a draft report (PDF) published Wednesday by the Institute for Clinical and Economic Review (ICER), an influential organization focused on evidence-based drug-cost analysis.

Specifically, the ICER report suggests that tafamidis—sold under the brands Vyndaqel and Vyndamax—should cost below or between $5,200 and $10,400 per year under two quality-adjusted life year (QALY) gained thresholds that are commonly used in cost-effectiveness reviews to help payers make decisions about drug coverage.

The range, even at its upper end, comes far below tafamidis’ current price, which is nearly $268,000 at the wholesale acquisition cost or around $194,000 after discounts. The tafamidis family has been a major growth driver for Pfizer, with sales up 36% last year to reach $3.3 billion.

In a statement to Fierce Pharma, Pfizer said it’s open to dialogue with all stakeholders about the value of ATTR-CM medicines, including with ICER.

“The use of QALY as a cost-effectiveness measure is well established, however, in rare diseases, this poses some challenges and bias particularly against elderly populations suffering from serious diseases who have a shorter life expectancy and less time to benefit from treatment,” Pfizer said.

As the only approved drugs for the rare heart disease, Vyndaqel and Vyndamax have the strongest recommendation in clinical guidelines. The New York pharma also pointed to clinical data showing the drug’s ability to reduce all-cause deaths and cardiovascular-related hospitalizations for ATTR-CM patients.

The draft report is now open for comments, and ICER plans to publish an updated evidence report on Sept. 5. Then, following a public meeting, the organization plans to publish the final report on Oct. 21.

The price range that ICER generated covers a class of drugs known as transthyretin stabilizer, which also includes BridgeBio’s investigational acoramidis. The California biotech, while awaiting an FDA decision in ATTR-CM in November, declined to comment on the ICER report.

ICER also conducted a preliminary analysis of Alnylam’s RNA interference therapy Amvuttra, which recently reported a positive phase 3 readout in ATTR-CM. But the draft report didn’t provide a cost-effectiveness price for Amvuttra because the existing top-line results from Alnylam’s HELIOS-B trial were not enough to perform such an analysis, ICER’s Chief Medical Officer, David Rind, told Fierce Pharma via email.

Amvuttra was launched in 2022 at an annual list price of $463,500 to treat another form of ATTR affecting the peripheral nerves.

Alnylam is expected to provide detailed data from HELIOS-B at the upcoming European Society of Cardiology annual meeting in late August and early September. Rind said ICER may have the necessary data by the time of the final report.

Before that, analysts at William Blair spotted a positive sign in ICER’s draft report for Amvuttra.

Pfizer got tafamidis approved based on data from the phase 3 ATTR-ACT trial showing it reduced the risk of death by 30% compared with placebo. But ICER noted that ATTR-CM patients today are being diagnosed earlier in their disease course. Even though a subgroup analysis of ATTR-ACT suggests greater benefit of tafamidis in less symptomatic patients, ICER argued that the magnitude of the benefit of tafamidis in this contemporary population is not firmly established.

As for acoramidis, the BridgeBio drug didn’t meet statistical significance on reduction of all-cause mortality in the phase 3 ATTRibute-CM trial. In its draft report, ICER also said, “any mortality benefit of acoramidis was small and of questionable statistical significance.”

By comparison, ICER acknowledged Amvuttra’s reported statistically significant 35.5% reduction in the risk of death, which included 40% of patients on background tafamidis.

Analysts are awaiting detailed data from HELIOS-B to see how early Amvuttra showed a survival benefit and how it performed when used in combination with tafamidis. For now, the William Blair team argued that ICER’s commentary “continues to bode well for [Amvuttra] positioning.”

Nevertheless, even if Amvuttra eventually got a higher price tag than tafamidis did in ICER’s final report, it would likely still need a major discount to be considered cost-effective given the Alnylam injection is already much pricier than Pfizer’s oral med.