Transthyretin amyloidosis (ATTR) has rapidly shifted from a rarely recognized, fatal condition into one of the most closely watched rare-disease markets in biopharma.
With multiple therapeutic entrants, distinct scientific platforms, and increasingly sophisticated payer strategies, ATTR now serves as a template for how innovation, diagnosis expansion, pricing, and access come together to shape a complex specialty category.
This deep dive draws on recent research into the ATTR space, collected via MMIT’s Payer Message Monitor across 100 payers and 150 panelists.
Understanding Transthyretin Amyloidosis
ATTR is caused by misfolded transthyretin (TTR) proteins that accumulate in tissues — especially the heart and peripheral nerves — leading to severe, progressive organ damage. It appears in two forms: hereditary ATTR (hATTR), which affects roughly 50,000 individuals globally, and wild-type ATTR (wtATTR), the far more common, age-related form which impacts more than 300,000 people worldwide.
The disease primarily presents as either ATTR-CM (cardiomyopathy) or ATTR-PN (polyneuropathy). Historically underdiagnosed, ATTR identification has accelerated dramatically as imaging, genetic testing, EMR-based alerts, and clinician awareness continues to evolve, turning what was once a hidden disorder into a rapidly expanding therapeutic field.
Four Key Players in the Dynamic ATTR Market
The market basket for ATTR is comprised of three gene silencers and two stabilizers, with many more in the pipeline. Here are the main players:
Pfizer’s Vyndamax (tafamidis): Vyndamax, Pfizer’s flagship stabilizer therapy, has set the benchmark in ATTR-CM by preventing TTR misfolding and slowing disease progression. Pfizer’s ATTR-ACT study demonstrated substantial reductions in mortality and cardiovascular hospitalizations, helping cement the brand’s leadership. Pfizer is phasing out Vyndaqel, a bioequivalent ATTR therapy that requires more frequent dosing, by the end of 2025. Vyndamax remains central to Pfizer’s strategy, supported by brand familiarity and strong physician confidence.
Alynylam’s Amvuttra (vutrisiran): In March 2025, Amvuttra became the only therapy currently approved for both hATTR-PN and ATTR-CM, using RNA interference to suppress TTR production. Quarterly dosing, the compelling mortality and CV outcomes demonstrated in Alynylam’s HELIOS-B trials, and the brand’s successful early commercialization are helping to position Alnylam as a leader in disease-modifying ATTR therapy. However, payers have expressed concerns about Amvuttra retaining the same high price point, despite transitioning from the ultra-rare ATTR-PN indication to the more common ATTR-CM indication. Some payers have requested discounts via contracting.
BridgeBio’s Attruby (acoramidis): Attruby entered the market in December 2024 as a high-value stabilizer alternative, with data from BridgeBio’s ATTRibute-CM trial showing robust mortality and hospitalization benefits and visible improvement as early as one month. Priced at approximately 10% less than Vyndamax, Attruby’s positioning blends clinical strength with economic value.
AstraZeneca’s Wainua (eplontersen): Wainua, an antisense therapy approved to treat hATTR-PN, reduces TTR production and improves neuropathy and quality of life. The company is currently running a Phase 3 ATTR-CM trial for eplontersen, CARDIO-TTRansform. In the meantime, AstraZeneca is advancing NI006, a monoclonal antibody targeting amyloid clearance, a new frontier in ATTR treatment. AstraZeneca is also investing heavily in IDN partnerships to expand diagnosis capabilities and build future patient pipelines.
Strategic Positioning and Access Tactics in ATTR
The major competitors in the ATTR space have adopted various strategies depending on their therapy’s strengths and weaknesses.
Pfizer’s strategy centers on proactive brand transition from Vyndaqel to Vyndamax. The company is leveraging its entrenched presence in cardiology, as well as physicians’ familiarity with its brands, to secure long-term share. In the wake of the IRA, Medicare patients have lower out-of-pocket costs, supporting adherence and patient continuity. Strong clinical confidence and established pathways reinforce Pfizer’s leadership position, even as competition intensifies.
Alnylam’s strategy centers on Amvuttra’s approval for both ATTR-CM and hATTR-PN. Along with dual indications, Amvuttra’s major differentiators include convenient quarterly dosing and its RNAi mechanism, which offers disease-modifying potential. BridgeBio’s narrative spans clinical strength and pricing discipline. BridgeBio is offering a lower WAC than Vyndamax, emphasizing affordability as well as clinical outcomes. The company is presenting itself as a rare-disease innovator with payer alignment in mind.
As for AstraZeneca, its strategy pairs scientific breadth with system-level patient-finding tools. Through AI-based screening, EMR algorithms and IDN engagement — as well as real-world evidence programs like MaesTTRo — AstraZeneca is building infrastructure designed to identify patients earlier, and hopefully to convert that diagnostic momentum into future therapeutic uptake.
Market Access Implications for Rare Disease
This deep dive into the complexities of the ATTR market offers a few key takeaways for other rare diseases:
- Early Diagnosis as a Market Enabler
Diagnostic innovation is dramatically increasing patient identification. From AI-driven EMR alerts to cardiology–neurology collaboration pathways, early diagnosis is no longer a support function. It is a core commercial lever, expanding the treatable population and accelerating initiation timelines.
- Pharmacy Benefit Shift
Payers are increasingly organizing ATTR therapies through the pharmacy benefit to simplify distribution, manage adherence programs, and standardize utilization management. This shift also reflects the complexity and touchpoint intensity of rare-disease support models.
- Pricing Pressure
Even in rare disease, competitive pricing and affordability considerations now shape decision-making. Affordability programs and real-world evidence requirements are becoming central to ATTR access. Payers are signaling a need for sustained functional improvement, hospitalization reduction, and real-world mortality benefit — not just clinical trial success.
- Modality Diversification
Stabilizers, RNAi therapies, antisense platforms, and antibody-based removal mechanisms are coexisting, highlighting how multimodal innovation can rapidly mature a market. ATTR is effectively running four scientific strategies simultaneously, offering learnings about how payers deal with differing mechanisms of action (MoAs).
- Rare Disease as a Scalable Model
The expansion of ATTR from underdiagnosed condition to multi-billion-dollar therapeutic ecosystem reflects the future of rare disease: precision science, payer alignment, diagnostic expansion, patient services, and real-world evidence working in parallel. ATTR is showing the playbook for scalable rare-disease commercialization.
ATTR amyloidosis has evolved from a rarely recognized disorder into one of the most sophisticated rare-disease commercial arenas. With four major players pursuing distinct strategies across mechanism, pricing, evidence, and diagnosis infrastructure, the space now represents the future of rare-disease commercialization — where access strategy, scientific differentiation, and patient-finding engines are as critical as clinical performance.
As the market grows and competition intensifies, ATTR stands as a model for building sustainable, patient-centered, clinically rigorous, and payer-aligned therapeutic ecosystems, offering a preview of how the next chapter of rare-disease innovation will unfold.
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