The Evolving Landscape of ATTR-CM: Key Drugs and Companies Leading the Charge

Transthyretin amyloid cardiomyopathy (ATTR-CM), once a rare and underdiagnosed cause of heart failure, has become a major focus of pharmaceutical innovation. With the first wave of therapies approved and a rich pipeline in late-stage development, ATTR-CM is now a rapidly evolving competitive space with significant market potential.

Approved Therapies: Leading the Way

The approval of tafamidis in 2019 marked a turning point in ATTR-CM treatment. Since then, other modalities have emerged, bringing variety in mechanisms, delivery, and potential outcomes.

(Vyndamax® / Vyndaqel® – Pfizer)

• Mechanism: TTR stabilizer
• Approved for: Both wild-type and hereditary ATTR-CM
• Differentiator: First-in-class, oral, once-daily treatment
• Data: Reduced all-cause mortality and cardiovascular-related hospitalizations in the ATTR-ACT trial
• Status: Market leader, but expensive (>$200,000/year), with reimbursement barriers in some countries

Vutrisiran (Amvuttra® – Alnylam)

• Mechanism: Next-gen subcutaneous RNAi
• Approved for: wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) (2025)
• Differentiator:  
  • Quarterly SC dosing, more convenient than IV patisiran
    • First RNAi therapeutic to reduce cardiovascular death, hospitalizations and urgent heart failure visits in adults with ATTR-CM
• Mechanism: transthyretin stabilizer
• Approved for: wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) (2024)
• Differentiator: First and only approved product with a label specifying near-complete stabilization of TTR

Acoramidis (Attruby™- BridgeBio)

• Mechanism: transthyretin stabilizer
• Approved for: wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) (2024)
• Differentiator: First and only approved product with a label specifying near-complete stabilization of TTR

The Late-Stage Pipeline: Who’s Next?

NTLA-2001 (Intellia Therapeutics/Regeneron)

• Mechanism: In vivo CRISPR-based gene editing
• Stage: Phase I
• Potential: Single-dose therapy to permanently reduce TTR production
• Outlook: Very early, but transformative if safe and effective

The NTLA-2001 CRISPR-based gene editing technology represents the next frontier in ATTR-CM treatment. 

Eplontersen (Ionis/AstraZeneca)

• Mechanism: Antisense oligonucleotide (ASO) targeting TTR mRNA
• Stage: Phase III (CARDIO-TTRansform trial)
• Differentiator: Monthly SC dosing with potential for broader use across ATTR spectrum

Eplontersen’s approach to reducing TTR production is expected to be a major competitor to Vutrisiran and Patisiran, with monthly dosing positioning it for widespread adoption. 

Market Dynamics & Competitive Outlook

The ATTR-CM space is rapidly becoming highly competitive, driven by:

• Multiple mechanisms of action (stabilization, gene silencing, editing)
• Route of administration differences (oral vs. IV vs. SC)
• Frequency and durability of dosing
• Cost and reimbursement challenges

Pfizer’s tafamidis currently leads the market, but with BridgeBio’s acoramidis showing strong data and Alnylam’s RNAi platforms advancing in cardiomyopathy, the market share may begin to shift as new options gain approval.

The potential for a one-time cure (CRISPR-based therapies) could further disrupt the landscape in the long term.

Market Opportunity

ATTR-CM is no longer a rare or little-known disease. Today, it’s a major focus for biotech companies. From drugs that stabilize the TTR protein to ones that silence the gene or even use gene editing, companies are exploring many ways to stop the harmful protein buildup in the heart. With both lives and billions of dollars on the line, this is an important area of drug development to keep an eye on.