After calling for a major discount for Pfizer’s popular transthyretin amyloid cardiomyopathy (ATTR-CM) med tafamidis, a U.S. drug cost watchdog has provided a final analysis that includes a smaller—yet still hefty—price reduction demand.

Pfizer’s tafamidis drugs, Vyndaqel and Vyndamax, need a minimum 85% discount from annual list prices of nearly $268,000 to meet commonly accepted cost-effectiveness thresholds, the Institute for Clinical and Economic Review (ICER) found in an updated ATTR-CM report (PDF) published Monday.

To meet the cost-effectiveness bar of between $100,000 and $150,000 per quality-adjusted life year (QALY) or equal value of life year gained, tafamidis and the transthyretin-stabilizing agent class it belongs to should cost between $13,600 to $39,000 a year, according to ICER. That means a discount between 85% to 95%.

The price numbers are higher compared with those included in a July draft report, in which ICER put the annual wholesale acquisition cost limits at $5,200 and $36,000 based on the same cost-effectiveness thresholds.

In a statement to Fierce Pharma, Pfizer again pointed to “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” when using QALY as a cost-effectiveness measure in rare disease.

The final report comes as the FDA is slated to decide on BridgeBio Pharma’s rival transthyretin stabilizer acoramidis next month and just a few days after Alnylam Pharmaceuticals filed its RNA silencer Amvuttra, aka vutrisiran, potentially disrupting the ATTR-CM market landscape.

The ICER price range covers both tafamidis and acoramidis but not Amvuttra. The Alnylam drug debuted in 2022 with an FDA approval in ATTR-polyneuropathy and an annual list price of $463,500.

The new evaluation includes several modeling adjustments compared with the draft. To explain the increase in price range, ICER’s chief medical officer David Rind, M.D., pointed to a change in the way mortality was estimated, including a recalibration based on how tafamidis’s survival benefit only started to show 18 months after treatment in the phase 3 ATTR-ACT trial, plus an error in the previous calculation of a subjective measurement of quality of life.

The final report again didn’t include a financial assessment of Amvuttra despite new presentation of results from the HELIOS-B trial showing the small-interfering RNA therapy could reduce the risk of death from any reason by 35% versus placebo through 42 months.

ICER gave the HELIOS-B data an “A” rating, indicating it has “high certainty that treatment with vutrisiran, compared with no disease-specific therapy or when added to tafamidis, provides a substantial net health benefit.”

However, Rind said via email that the organization still doesn’t have enough data to build an economic model for Amvuttra. For example, for patients with NYHA class III heart failure, ICER currently lacks information on the likelihood of patients staying stable, improving or worsening all during a single cycle of the model, Rind explained. But he also noted that this information is “reasonably likely to become available eventually,” because European health assessments will ask for it.

In the final report, ICER also argued that it’s impossible to compare the net health benefits between Amvuttra and the stabilizers given the different patient characteristics.

“Additionally, given the findings in HELIOS-B, it may be that a primary issue will be whether combination therapy is superior to monotherapy,” the organization said in the report.

As such, as part of its policy recommendations, ICER said researchers should make efforts to establish the comparative profiles of the three drugs.

“Realistically, I don’t think we’re going to really be sure of the answer to this without more [randomized clinical trials],” Rind said.