ATTR Amyloidosis Clinical Trial Tracker

Active ATTR Clinical Trials

The ATTR Treatment Landscape: Five Mechanisms Competing

ATTR amyloidosis treatment has evolved from supportive care to a crowded competitive space over the past decade. Five distinct therapeutic mechanisms now have approved or late-stage drugs:

1. RNA Interference (RNAi) — Alnylam Dominance

Alnylam Pharmaceuticals pioneered RNAi-based TTR silencing. Their first drug, patisiran (Onpattro), uses lipid nanoparticles to deliver siRNA to hepatocytes, reducing TTR production by ~80%. It received FDA approval for ATTRv polyneuropathy in 2018 — the first-ever RNAi therapy to reach market.

Vutrisiran (Amvuttra) is Alnylam's next-generation GalNAc-conjugated siRNA, enabling quarterly subcutaneous injection vs. monthly IV infusion for patisiran. APOLLO-B (2022) demonstrated vutrisiran's benefit in ATTR-CM, establishing a second approved indication and extending Alnylam's franchise into the much larger cardiomyopathy market.

Alnylam's registry studies (DemonsTTRate, ConTTRibute) are building the real-world evidence base and capturing longitudinal patient data that competitors will have to counter with their own registries.

2. TTR Stabilizers — Pfizer and Bayer

TTR stabilizers prevent the tetramer from dissociating into amyloidogenic monomers. Pfizer's tafamidis (Vyndaqel/Vyndamax) established the proof-of-concept for ATTR-CM treatment with the ATTR-ACT trial (2018) — the first Phase 3 to show survival benefit in ATTR-CM. Tafamidis has become a blockbuster ($2.4B+ annual revenue) and the current standard of care for ATTR-CM.

Acoramidis (formerly AG10), developed by BridgeBio and now licensed to Bayer, is the next-generation stabilizer — with higher TTR binding affinity and near-complete stabilization. The ATTRibute-CM Phase 3 demonstrated significant improvements in functional capacity and hospitalization vs placebo. Bayer's real-world study (NCT07235462) is building the post-approval evidence base for acoramidis.

3. Antisense Oligonucleotides (ASO) — AstraZeneca/Ionis

Eplontersen (Wainua), developed by Ionis and licensed to AstraZeneca, is a GalNAc-ASO that reduces hepatic TTR production via mRNA degradation. FDA-approved for ATTRv polyneuropathy (2023). AstraZeneca's observational study (NCT06465810) covers eplontersen and the full ATTR treatment landscape, reflecting AZ's intent to build real-world evidence across the ATTR disease spectrum.

4. In Vivo Gene Editing — Intellia (CRISPR)

Intellia Therapeutics' NTLA-2001 is the most transformative program in the ATTR space. A single intravenous infusion delivers CRISPR/Cas9 components to hepatocytes via lipid nanoparticles, permanently editing the TTR gene. Phase 1 data showed ~90% TTR reduction sustained at 24 months after a single dose. The MAGNITUDE Phase 3 trial is recruiting ATTRv polyneuropathy patients for a head-to-head comparison.

The strategic significance for BD: if NTLA-2001 succeeds, it defines a new competitive tier — a one-dose curative therapy vs. chronic dosing strategies. All current commercial TTR-targeting drugs require continuous treatment. A durable single-dose gene editing therapy would restructure the market and create enormous licensing/acquisition pressure on gene editing platforms.

5. Amyloid Clearance — Emerging Strategies

Beyond preventing TTR production, researchers are investigating therapies that actively remove deposited amyloid from tissues. CAEL-101 (anti-amyloid antibody, Cabaletta Bio) showed early activity in AL amyloidosis; TTR-directed antibodies targeting misfolded TTR oligomers are in early development. Amyloid clearance could complement TTR silencing by addressing existing deposits while new production is blocked.

The ATTR-CM Underdiagnosis Problem

ATTR-CM remains significantly underdiagnosed. Studies suggest 5–10% of patients with heart failure with preserved ejection fraction (HFpEF) have ATTR-CM — a population measured in millions globally. Diagnosis historically required invasive endomyocardial biopsy, but scintigraphy with technetium-labeled tracers (PYP or DPD scans) can diagnose ATTRwt-CM non-invasively.

AI-based ECG screening is the next frontier. The INSPECT trial (Yale, NCT07398950) is validating an AI platform for ATTR-CM screening using standard 12-lead ECGs — a non-invasive, widely available test. If validated, AI ECG screening could dramatically expand the diagnosed ATTR-CM population, creating a larger treated market. This is a key pipeline monitoring point for any cardiovascular or rare disease BD team.

Related Disease and Sponsor Pages

• Amyloidosis Clinical Trials — Full Landscape
• Heart Failure Clinical Trials
• Alnylam Pharmaceuticals — Full Pipeline
• Rare Disease Clinical Trials

Frequently Asked Questions

How is ATTR amyloidosis diagnosed?

ATTRwt-CM (wild-type cardiomyopathy) is diagnosed by: (1) technetium pyrophosphate (PYP) scintigraphy showing Grade 2–3 cardiac uptake with a cardiac-to-contralateral ratio ≥1.5, combined with (2) absence of monoclonal protein on serum/urine immunofixation (to exclude AL amyloidosis). This non-biopsy algorithm is now the standard approach. ATTRv is confirmed by genetic testing for TTR pathogenic variants. Cardiac MRI with gadolinium enhancement shows characteristic late gadolinium enhancement patterns. Endomyocardial biopsy with Congo red staining and immunohistochemistry remains the gold standard when non-invasive testing is equivocal.

What are the ATTR disease monitoring keywords for ClinicalTrials.gov?

Comprehensive ATTR coverage requires multiple search terms: "transthyretin amyloidosis", "ATTR amyloidosis", "ATTR-CM", "ATTRv", "hATTR", "wild-type amyloidosis", "TTR amyloidosis", plus individual drug names: patisiran, vutrisiran, eplontersen, tafamidis, acoramidis, NTLA-2001. DataLookout monitors all ATTR-related trials daily across all naming conventions.