Tafamidis Meglumine

In its final analysis of Pfizer Inc. 's widely used drug for transthyroid amyloid cardiomyopathy (ATRCM), the U.S. drug cost regulator called for a reduction of at least 85 percent from its current list price of nearly $268,000 a year to meet generally accepted cost-effectiveness standards. The conclusion, made official in the latest ATRCM report released Monday by the Institute for Clinical and Economic Review (ICER), makes clear that Pfizer's two tafetamines, Vyndaqel and Vyndamax, are subject to the discount requirement. According to ICER's data analysis, in order to meet the cost-effectiveness criteria of between $100,000 and $150,000 per quality-adjusted life year (QALY) or equivalent life year acquired, the annual cost of Tarfamides and the thyrotropin stabilizer category to which it belongs should be adjusted to between $13,600 and $39,000. That means a price cut of between 85 and 95 per cent. The proposed annual cost range is revised up from a preliminary draft report in July. In its response, Pfizer reiterated the challenges and biases it faces in using QALEs as a cost-effectiveness measure for rare diseases, particularly for older patients who have a shorter life expectancy and limited time to benefit from treatment. In addition, the report comes at a time when the FDA is about to make a decision on BridgeBio Pharmaceuticals' competing drug acoramidis, and Alnylam Pharmaceuticals recently submitted an application for its RNA silencer Amvuttra (vutrisiran). This could further affect the competitive landscape of the ATRCM market. It is worth noting that ICER's price assessment covered Tafamidi and acoramidis, but did not include Amvuttra. Although Amvuttra was approved by the FDA for the treatment of ATR polyneuropathy in 2022 and has an annual price tag of $463,500, ICER said there is still not enough data to build an economic model for it. ICER's chief medical officer, Dr. David Rind, noted that the reasons for the price range adjustment include a change in the mortality estimate methodology and the correction of a calculation error in the previous quality of life assessment. At the same time, he highlighted the difficulty in economic evaluation of Amvuttra, especially the lack of data on the prediction of disease change in patients with NYHA Class III heart failure. However, he expects that the information may eventually be made public to meet the requirements of the European health assessment. In the final report, ICER also raised the complexity of comparing the net health benefits of Amvuttra versus stabilizers, noting that the question of the advantages of combination therapy versus monotherapy needs further study. To that end, the group recommends that researchers work to build a comparative profile of the three drugs and stresses the importance of randomized clinical trials to answer this question.

iStock/ jauhari1 As it nears a crucial FDA action date for its transthyretin amyloid cardiomyopathy candidate, BridgeBio focuses on its late-stage pipeline. Bay area–based biotech BridgeBio, founded in 2015 to be a bridge between promising early-stage academic work and patients with genetic diseases, is now a growing commercial enterprise, with two products on the market and another expecting an FDA decision by the end of November. As such, the company is making strategic moves, spinning out some assets into two new companies, cutting an entire gene therapy program and focusing its remaining resources on its late-stage programs in transthyretin amyloid cardiomyopathy and achondroplasia, which analysts say are key to BridgeBio’s success. “We have the capability, by our tenth birthday, to have had six approved products for a billion-plus dollar market,” Neil Kumar, the company’s charismatic founder and CEO told BioSpace . “So that’s a very, very productive engine.” However, commercial success requires the company to make some adjustments, Kumar continued. “Our investors would like to see us focus our resources to show that we can commercialize,” Kumar said, with a specific focus on the company’s later-stage pipeline. “We’ve shown we can do R&D, but now we have to show we can commercialize and build a business against these products.” To satisfy these investors, BridgeBio has adopted a hub-and-spoke model. In May 2024, it spun out its KRAS-focused cancer portfolio into BridgeBio Oncology Therapeutics , which it endowed with $200 million in initial funding. And last month, BridgeBio debuted GondolaBio to further develop early-stage assets for tuberous sclerosis complex, erythropoietic protoporphyria and alpha-A1 antitrypsin deficiency. Then this week, the company announced that it is discontinuing development of its gene therapy candidate BBP-631 after it failed to show “transformational results” in a mid-stage study in congenital adrenal hyperplasia (CAH). “The data we generated did not suggest that our efforts would result in a meaningful step forward for patients as compared to what we think standard of care will be in the coming years,” Kumar said. “Therefore, we felt our efforts would be better applied to other areas of unmet need,” though the company is seeking a partnership to continue development of BBP-631 and other next-generation gene therapies for CAH. That leaves the company’s two approved products— Nulibry for molybdenum cofactor deficiency type A and the targeted cancer treatment Truseltiq (infigratinib), both approved in 2021—and four assets in late-stage development. First and foremost, BridgeBio is gearing up for a Nov. 29 FDA action date on its transthyretin amyloid cardiomyopathy (ATTR-CM) hopeful, acoramidis. At the same time, the company is continuing Phase III development on three more drug candidates —infigratinib for achondroplasia, BBP-418 for limb-girdle muscular dystrophy type 21/R9 and encaleret for autosomal dominant hypocalcemia type 1. Kostas Biliouris, director of biotech equity research at BMO Capital Markets, noted that the primary interest in BridgeBio is in acoramidis and infigratinib. “The other spinout companies are probably increasing efficiency” for these late-stage products because they effectively remove from BridgeBio’s portfolio “something that investors are not focused on,” he told BioSpace . The Path to Success If approved in November, acoramidis will be going up in the ATTR-CM market against Pfizer’s tafamidis, sold as Vyndaqel and Vyndamax, which Biliouris said is well-established in the market. Like tafamidis, acoramidis is a transthyretin stabilizer. Biliouris said that while acoramidis may be “incrementally better” than tafamidis, it needs to be dosed twice per day, compared to once per day for Pfizer’s drugs, which may limit uptake. In addition, Biliouris said, Pfizer has demonstrated that tafamidis can reduce the risk of mortality, whereas acoramidis did not show a statistically significant effect on this measure. In a survey of 30 physicians conducted by BMO Capital Markets, 50% of doctors said the efficacy is similar between acoramidis and tafamidis, while 40% believed acoramidis to be incrementally better, Biliouris shared. “That’s why it’s not an easy story.” If BridgeBio does secure FDA approval for acoramidis, the company will then need to beat sales expectations in 2025, Biliouris said, estimating these to be about $165 million in the U.S. “If BridgeBio can beat that number, it will be great,” he told BioSpace . “It will help the stock and the story. If not, it will be challenging.” Some of the drug’s success could also be tied to whether or not tafamidis goes generic in 2028 or 2035, Biliouris noted, adding that this won’t be known until 2028. Another piece of the puzzle, according to Biliouris, is infigratinib, which if approved, will go up against BioMarin’s Voxzogo in the achondroplasia space. BridgeBio is anticipating a readout for the drug in late 2025, according to Biliouris. This trial needs to meet its primary endpoint and show a good safety profile, he said. “Usually, this drug treats kids and safety is very sensitive here.” It also “needs to be at least as good, if not better, than its main competitor,” Voxzogo, Biliouris continued, and like acoramidis, will also need to beat sales expectations. Kumar, for one, is confident in BridgeBio’s future success, noting that its ultimate goal is “to serve as many patients as possible across as many indications that effectively allow us to do high probability drug discovery development. What some companies would do [in BridgeBio’s position] is they would push pause,” he said. “But I don’t believe in pushing pause.”