J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

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Review

Volume 18, Number 7, July 2026, pages 421-436

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: Current Evidence and Emerging Strategies

↓ Figure 1. Amyloidogenic cascade in transthyretin amyloid cardiomyopathy and the points targeted by each therapeutic class. TTR: transthyretin; siRNA: small interfering RNA; ASO: antisense oligonucleotide; CRISPR: clustered regularly interspaced short palindromic repeats; TUDCA: tauroursodeoxycholic acid.

↓ Figure 2. Diagnostic and treatment-selection algorithm for transthyretin amyloid cardiomyopathy. ATTR-CM: transthyretin amyloid cardiomyopathy; NYHA: New York Heart Association; LV: left ventricular; HFpEF: heart failure with preserved ejection fraction; PYP: technetium-99m pyrophosphate; DPD: 3,3-diphosphono-1,2-propanodicarboxylic acid; HMDP: hydroxymethylene diphosphonate; ECG: electrocardiogram.

↓ Figure 3. Primary or key composite hazard ratios from the pivotal disease-modifying therapy trials in ATTR-CM. Endpoints, follow-up durations, and analytic methods differ across trials and no head-to-head comparisons exist, so the estimates are not directly comparable. Created by the authors. CI: confidence interval; ATTR-CM: transthyretin amyloid cardiomyopathy; CV: cardiovascular.

↓ **Table 1.** Major Clinical Trials of Tafamidis in ATTR-CM
Study	Trial name	Design	Sample size	Duration	Primary endpoint	Key outcome
Cardiovascular hospitalizations (CV hosp) refer to hospital admissions for cardiovascular causes, including worsening heart failure, arrhythmias, acute coronary syndromes, or other cardiac events requiring hospitalization. ATTR-CM: transthyretin amyloid cardiomyopathy; RCT: randomized controlled trial; HR: hazard ratio; CI: confidence interval; RR: relative risk; NYHA: New York Heart Association.
Maurer et al, 2018 [12]	ATTR-ACT	Phase 3 RCT	441	30 months	Composite of all-cause mortality and cardiovascular hospitalizations	Tafamidis reduced all-cause mortality (HR 0.70; 95% CI, 0.51–0.96) and decreased the annual rate of cardiovascular hospitalizations (0.48 vs 0.70 per year; RR 0.68, 95% CI, 0.56–0.81) compared with placebo
Damy et al, 2020 [14]	ATTR-ACT open-label extension	Open-label extension	400+	50+ months	Long-term survival	Continuous tafamidis from baseline was associated with longer median survival; median survival was not reached in the continuous group versus 35.8 months with delayed initiation
Elliott et al, 2023 [15]	NYHA III post-hoc analysis of ATTR-ACT	Post-hoc analysis	142	About 5 years	All-cause mortality	In patients with NYHA class III symptoms at baseline, continuous tafamidis reduced mortality risk by 36% compared with delayed treatment (HR 0.64; 95% CI, 0.41–0.99)

↓ Table 1. Major Clinical Trials of Tafamidis in ATTR-CM

Study

Trial name

Design

Sample size

Duration

Primary endpoint

Key outcome

Cardiovascular hospitalizations (CV hosp) refer to hospital admissions for cardiovascular causes, including worsening heart failure, arrhythmias, acute coronary syndromes, or other cardiac events requiring hospitalization. ATTR-CM: transthyretin amyloid cardiomyopathy; RCT: randomized controlled trial; HR: hazard ratio; CI: confidence interval; RR: relative risk; NYHA: New York Heart Association.

Maurer et al, 2018 [12]

ATTR-ACT

Phase 3 RCT

441

30 months

Composite of all-cause mortality and cardiovascular hospitalizations

Tafamidis reduced all-cause mortality (HR 0.70; 95% CI, 0.51–0.96) and decreased the annual rate of cardiovascular hospitalizations (0.48 vs 0.70 per year; RR 0.68, 95% CI, 0.56–0.81) compared with placebo

Damy et al, 2020 [14]

ATTR-ACT open-label extension

Open-label extension

400+

50+ months

Long-term survival

Continuous tafamidis from baseline was associated with longer median survival; median survival was not reached in the continuous group versus 35.8 months with delayed initiation

Elliott et al, 2023 [15]

NYHA III post-hoc analysis of ATTR-ACT

Post-hoc analysis

142

About 5 years

All-cause mortality

In patients with NYHA class III symptoms at baseline, continuous tafamidis reduced mortality risk by 36% compared with delayed treatment (HR 0.64; 95% CI, 0.41–0.99)

↓ **Table 2.** Major Clinical Trials of Acoramidis in ATTR-CM
Study	Trial name	Design	Sample size	Duration	Primary endpoint	Key outcome
Cardiovascular hospitalizations (CV hosp) refer to hospital admissions for cardiovascular causes. RCT: randomized controlled trial; HR: hazard ratio; CI: confidence interval; NT-proBNP: N-terminal pro-B-type natriuretic peptide; ATTR-CM: transthyretin amyloid cardiomyopathy.
Gillmore et al. [18]	ATTRibute-CM	Phase 3 RCT	632	30 months	Hierarchical composite endpoint	Acoramidis improved the hierarchical composite endpoint (all-cause mortality, cardiovascular hospitalizations, NT-proBNP change, and 6-min walk distance) versus placebo (win ratio, 1.8; 95% CI, 1.4–2.2); all-cause mortality or first cardiovascular hospitalization occurred less frequently with acoramidis (HR, 0.64; 95% CI, 0.50–0.83)
Judge et al, 2025 [12]	ATTRibute-CM open-label extension	Open-label extension	600+	42 months	Composite of all-cause mortality and cardiovascular hospitalizations	Long-term treatment with acoramidis reduced the risk of all-cause mortality or first cardiovascular hospitalization (HR, 0.57; 95% CI, 0.46–0.72) and maintained functional capacity measured by 6-min walk distance and quality of life over 42 months
Endo et al, 2026 [19]	Japanese phase 3 acoramidis study	Phase 3 open-label	25	30 months	Safety and efficacy	In Japanese patients with ATTR-CM, acoramidis showed favorable safety with no deaths reported over the 30-month study period and improvements in functional status and quality-of-life measures

↓ Table 2. Major Clinical Trials of Acoramidis in ATTR-CM

Study

Trial name

Design

Sample size

Duration

Primary endpoint

Key outcome

Cardiovascular hospitalizations (CV hosp) refer to hospital admissions for cardiovascular causes. RCT: randomized controlled trial; HR: hazard ratio; CI: confidence interval; NT-proBNP: N-terminal pro-B-type natriuretic peptide; ATTR-CM: transthyretin amyloid cardiomyopathy.

Gillmore et al. [18]

ATTRibute-CM

Phase 3 RCT

632

30 months

Hierarchical composite endpoint

Acoramidis improved the hierarchical composite endpoint (all-cause mortality, cardiovascular hospitalizations, NT-proBNP change, and 6-min walk distance) versus placebo (win ratio, 1.8; 95% CI, 1.4–2.2); all-cause mortality or first cardiovascular hospitalization occurred less frequently with acoramidis (HR, 0.64; 95% CI, 0.50–0.83)

Judge et al, 2025 [12]

ATTRibute-CM open-label extension

Open-label extension

600+

42 months

Composite of all-cause mortality and cardiovascular hospitalizations

Long-term treatment with acoramidis reduced the risk of all-cause mortality or first cardiovascular hospitalization (HR, 0.57; 95% CI, 0.46–0.72) and maintained functional capacity measured by 6-min walk distance and quality of life over 42 months

Endo et al, 2026 [19]

Japanese phase 3 acoramidis study

Phase 3 open-label

30 months

Safety and efficacy

In Japanese patients with ATTR-CM, acoramidis showed favorable safety with no deaths reported over the 30-month study period and improvements in functional status and quality-of-life measures

↓ **Table 3.** Gene silencing Therapies in ATTR-CM
Study	Trial name	Agent	Route	Dosing	Sample size	Duration	Key outcome
ATTR-CM: transthyretin amyloid cardiomyopathy; IV: intravenous; SC: subcutaneous; HR: hazard ratio; CI: confidence interval; NT-proBNP: N-terminal pro-B-type natriuretic peptide.
Maurer et al, 2023 [22]	APOLLO-B	Patisiran	IV	Every 3 weeks	360	12 months	Patisiran attenuated the decline in 6-min walk distance versus placebo (treatment effect about 15 m) and preserved health-related quality of life, with favorable trends in cardiac biomarkers including NT-proBNP and high-sensitivity troponin T
Fontana et al, 2025 [9]	HELIOS-B	Vutrisiran	SC	Every 3 months	664	30 months	Vutrisiran improved the hierarchical composite endpoint with win ratio of 1.7 (95% CI, 1.4–2.1), reducing the risk of all-cause death or recurrent cardiovascular events by approximately 33% (HR, 0.67; 95% CI, 0.52–0.87)
Coelho et al, 2023 [26]	NEURO-TTRansform	Eplontersen	SC	Monthly	168	18 months	Eplontersen slowed neuropathy progression; exploratory cardiac analyses showed reductions in NT-proBNP and stabilization of global longitudinal strain and left ventricular wall thickness

↓ Table 3. Gene silencing Therapies in ATTR-CM

Study

Trial name

Agent

Route

Dosing

Sample size

Duration

Key outcome

ATTR-CM: transthyretin amyloid cardiomyopathy; IV: intravenous; SC: subcutaneous; HR: hazard ratio; CI: confidence interval; NT-proBNP: N-terminal pro-B-type natriuretic peptide.

Maurer et al, 2023 [22]

APOLLO-B

Patisiran

Every 3 weeks

360

12 months

Patisiran attenuated the decline in 6-min walk distance versus placebo (treatment effect about 15 m) and preserved health-related quality of life, with favorable trends in cardiac biomarkers including NT-proBNP and high-sensitivity troponin T

Fontana et al, 2025 [9]

HELIOS-B

Vutrisiran

Every 3 months

664

30 months

Vutrisiran improved the hierarchical composite endpoint with win ratio of 1.7 (95% CI, 1.4–2.1), reducing the risk of all-cause death or recurrent cardiovascular events by approximately 33% (HR, 0.67; 95% CI, 0.52–0.87)

Coelho et al, 2023 [26]

NEURO-TTRansform

Eplontersen

Monthly

168

18 months

Eplontersen slowed neuropathy progression; exploratory cardiac analyses showed reductions in NT-proBNP and stabilization of global longitudinal strain and left ventricular wall thickness

↓ **Table 4.** Monoclonal Antibody Trials in ATTR Amyloidosis
Study	Trial name	Antibody	Target	Phase	Sample size	Key finding	Status
TTR: transthyretin; MRI: magnetic resonance imaging; NT-proBNP: N-terminal pro-B-type natriuretic peptide; GLS: global longitudinal strain.
Garcia-Pavia et al, 2023 [36]	NI006 phase 1	NI006 (ALXN2220)	Aggregated TTR	1	41	Monthly NI006 infusions (up to 60 mg/kg) were well tolerated. At doses ≥ 10 mg/kg, cardiac imaging demonstrated substantial reductions in myocardial amyloid burden with decreases in NT-proBNP and high-sensitivity troponin T	Phase 2/3 ongoing
Richards et al, 2024 [37]	PRX004 phase 1 dose-escalation	PRX004 (coramitug, NNC6019-0001)	Misfolded TTR	1	26	PRX004 was well tolerated with dose-proportional pharmacokinetics. Exploratory analyses suggested stabilization or improvement in global longitudinal strain and neuropathy impairment scores over 9 months	Phase 2 ongoing (NCT05442047)

↓ Table 4. Monoclonal Antibody Trials in ATTR Amyloidosis

Study

Trial name

Antibody

Target

Phase

Sample size

Key finding

Status

TTR: transthyretin; MRI: magnetic resonance imaging; NT-proBNP: N-terminal pro-B-type natriuretic peptide; GLS: global longitudinal strain.

Garcia-Pavia et al, 2023 [36]

NI006 phase 1

NI006 (ALXN2220)

Aggregated TTR

Monthly NI006 infusions (up to 60 mg/kg) were well tolerated. At doses ≥ 10 mg/kg, cardiac imaging demonstrated substantial reductions in myocardial amyloid burden with decreases in NT-proBNP and high-sensitivity troponin T

Phase 2/3 ongoing

Richards et al, 2024 [37]

PRX004 phase 1 dose-escalation

PRX004 (coramitug, NNC6019-0001)

Misfolded TTR

PRX004 was well tolerated with dose-proportional pharmacokinetics. Exploratory analyses suggested stabilization or improvement in global longitudinal strain and neuropathy impairment scores over 9 months

Phase 2 ongoing (NCT05442047)

↓ **Table 5.** CRISPR-Cas9 Gene Editing Trials
Study	Trial name	Population	Sample size	Dose	TTR reduction	Duration	Key outcome	Safety
CRISPR: clustered regularly interspaced short palindromic repeats; TTR: transthyretin; ATTRv-PN: hereditary ATTR with polyneuropathy; ATTR-CM: transthyretin amyloid cardiomyopathy; NT-proBNP: N-terminal pro-B-type natriuretic peptide; GLS: global longitudinal strain.
Gillmore et al, 2021 [38]	NTLA-2001 phase 1 ATTRv-PN	Hereditary ATTR with polyneuropathy	36	0.3–1.0 mg/kg	Up to 93%	12 months	Single-dose NTLA-2001 achieved up to about 93% sustained reduction in serum TTR at 12 months	Well tolerated; mild to moderate infusion-related reactions were the most common adverse events
Fontana et al, 2024 [39]	Nexiguran ziclumeran phase 1 ATTR-CM	ATTR cardiomyopathy	36	0.7–1.0 mg/kg	Up to 90%	24 months	Single-dose nex-z produced up to about 90% sustained TTR reduction over 24 months with improvements or stabilization in functional capacity and cardiac biomarkers	Mild infusion reactions; well tolerated with no drug-related serious adverse events

↓ Table 5. CRISPR-Cas9 Gene Editing Trials

Study

Trial name

Population

Sample size

Dose

TTR reduction

Duration

Key outcome

Safety

CRISPR: clustered regularly interspaced short palindromic repeats; TTR: transthyretin; ATTRv-PN: hereditary ATTR with polyneuropathy; ATTR-CM: transthyretin amyloid cardiomyopathy; NT-proBNP: N-terminal pro-B-type natriuretic peptide; GLS: global longitudinal strain.

Gillmore et al, 2021 [38]

NTLA-2001 phase 1 ATTRv-PN

Hereditary ATTR with polyneuropathy

0.3–1.0 mg/kg

Up to 93%

12 months

Single-dose NTLA-2001 achieved up to about 93% sustained reduction in serum TTR at 12 months

Well tolerated; mild to moderate infusion-related reactions were the most common adverse events

Fontana et al, 2024 [39]

Nexiguran ziclumeran phase 1 ATTR-CM

ATTR cardiomyopathy

0.7–1.0 mg/kg

Up to 90%

24 months

Single-dose nex-z produced up to about 90% sustained TTR reduction over 24 months with improvements or stabilization in functional capacity and cardiac biomarkers

Mild infusion reactions; well tolerated with no drug-related serious adverse events

↓ **Table 6.** Evidence Grading of Disease-Modifying and Investigational Therapies for ATTR-CM
Agent	Mechanism class	Highest phase in ATTR-CM	Regulatory status (ATTR-CM)	Primary endpoint type	Mortality or CV-hospitalization benefit demonstrated
Status reflects ATTR-CM unless otherwise noted and varies by jurisdiction and date. HR: hazard ratio; CV: cardiovascular; ATTRv-PN: hereditary ATTR with polyneuropathy; GLS: global longitudinal strain; TUDCA: tauroursodeoxycholic acid; NSAID: nonsteroidal anti-inflammatory drug; EGCG: epigallocatechin-3-gallate; FDA: Food and Drug Administration; EMA: European Medicines Agency; PMDA: Pharmaceuticals and Medical Devices Agency; RCT: randomized controlled trial; siRNA: small interfering RNA; CRISPR: clustered regularly interspaced short palindromic repeats; ATTR-CM: transthyretin amyloid cardiomyopathy.
Tafamidis	Tetramer stabilizer	Phase 3 (ATTR-ACT)	Approved (FDA, EMA, PMDA)	Finite composite of all-cause mortality and CV hospitalization	Yes; all-cause mortality HR 0.70 (0.51–0.96)
Acoramidis	Tetramer stabilizer	Phase 3 (ATTRibute-CM)	Approved (FDA 2024; other regions vary)	Hierarchical win-ratio composite	CV outcome benefit; all-cause mortality alone not independently significant
Patisiran	siRNA gene silencer	Phase 3 (APOLLO-B)	Approved for ATTRv-PN; not approved for ATTR-CM	6-min walk distance (continuous)	No mortality benefit shown in ATTR-CM
Vutrisiran	siRNA gene silencer	Phase 3 (HELIOS-B)	Approved for ATTR-CM (FDA 2025)	Hierarchical composite	Yes; all-cause mortality or recurrent CV events HR 0.67 (0.52–0.87)
Eplontersen	Antisense oligonucleotide gene silencer	Phase 3 ongoing (CARDIO-TTRansform)	Approved for ATTRv-PN; ATTR-CM under study	Hard clinical endpoints (pending)	Pending
Inotersen	Antisense oligonucleotide gene silencer	Phase 3 in ATTRv-PN (NEURO-TTR)	Approved for ATTRv-PN; not for ATTR-CM	Neuropathy endpoints (not cardiac)	Not established in ATTR-CM; use limited by safety
Doxycycline plus TUDCA	Fibril disruption	Phase 3 (DOXY-TUDCA)	Not approved	Survival	No; negative phase 3 trial
NI006 (ALXN2220)	Anti-amyloid monoclonal antibody	Phase 1 complete; phase 3 ongoing	Investigational	Imaging and biomarker (phase 1)	Not yet; outcome trials ongoing
PRX004 (coramitug)	Anti-amyloid monoclonal antibody	Phase 1 complete; phase 2 ongoing	Investigational	Exploratory (GLS, biomarkers)	Not established
NTLA-2001/nexiguran ziclumeran	CRISPR-Cas9 gene editing	Phase 1 complete; phase 3 ongoing	Investigational	TTR knockdown; clinical endpoints pending	Not yet established
Diflunisal	Tetramer stabilizer (NSAID)	RCT in ATTRv-PN; observational in ATTR-CM	Not approved for ATTR-CM (used off-label)	Neuropathy endpoint (PN trial)	No cardiac RCT; not established
EGCG (green tea)	Fibril-formation inhibitor (polyphenol)	Small observational studies only	Not a recognized drug indication	Imaging surrogate	No; uncontrolled data only

↓ Table 6. Evidence Grading of Disease-Modifying and Investigational Therapies for ATTR-CM

Agent

Mechanism class

Highest phase in ATTR-CM

Regulatory status (ATTR-CM)

Primary endpoint type

Mortality or CV-hospitalization benefit demonstrated

Status reflects ATTR-CM unless otherwise noted and varies by jurisdiction and date. HR: hazard ratio; CV: cardiovascular; ATTRv-PN: hereditary ATTR with polyneuropathy; GLS: global longitudinal strain; TUDCA: tauroursodeoxycholic acid; NSAID: nonsteroidal anti-inflammatory drug; EGCG: epigallocatechin-3-gallate; FDA: Food and Drug Administration; EMA: European Medicines Agency; PMDA: Pharmaceuticals and Medical Devices Agency; RCT: randomized controlled trial; siRNA: small interfering RNA; CRISPR: clustered regularly interspaced short palindromic repeats; ATTR-CM: transthyretin amyloid cardiomyopathy.

Tafamidis

Tetramer stabilizer

Phase 3 (ATTR-ACT)

Approved (FDA, EMA, PMDA)

Finite composite of all-cause mortality and CV hospitalization

Yes; all-cause mortality HR 0.70 (0.51–0.96)

Acoramidis

Tetramer stabilizer

Phase 3 (ATTRibute-CM)

Approved (FDA 2024; other regions vary)

Hierarchical win-ratio composite

CV outcome benefit; all-cause mortality alone not independently significant

Patisiran

siRNA gene silencer

Phase 3 (APOLLO-B)

Approved for ATTRv-PN; not approved for ATTR-CM

6-min walk distance (continuous)

No mortality benefit shown in ATTR-CM

Vutrisiran

siRNA gene silencer

Phase 3 (HELIOS-B)

Approved for ATTR-CM (FDA 2025)

Hierarchical composite

Yes; all-cause mortality or recurrent CV events HR 0.67 (0.52–0.87)

Eplontersen

Antisense oligonucleotide gene silencer

Phase 3 ongoing (CARDIO-TTRansform)

Approved for ATTRv-PN; ATTR-CM under study

Hard clinical endpoints (pending)

Pending

Inotersen

Antisense oligonucleotide gene silencer

Phase 3 in ATTRv-PN (NEURO-TTR)

Approved for ATTRv-PN; not for ATTR-CM

Neuropathy endpoints (not cardiac)

Not established in ATTR-CM; use limited by safety

Doxycycline plus TUDCA

Fibril disruption

Phase 3 (DOXY-TUDCA)

Not approved

Survival

No; negative phase 3 trial

NI006 (ALXN2220)

Anti-amyloid monoclonal antibody

Phase 1 complete; phase 3 ongoing

Investigational

Imaging and biomarker (phase 1)

Not yet; outcome trials ongoing

PRX004 (coramitug)

Anti-amyloid monoclonal antibody

Phase 1 complete; phase 2 ongoing

Investigational

Exploratory (GLS, biomarkers)

Not established

NTLA-2001/nexiguran ziclumeran

CRISPR-Cas9 gene editing

Phase 1 complete; phase 3 ongoing

Investigational

TTR knockdown; clinical endpoints pending

Not yet established

Diflunisal

Tetramer stabilizer (NSAID)

RCT in ATTRv-PN; observational in ATTR-CM

Not approved for ATTR-CM (used off-label)

Neuropathy endpoint (PN trial)

No cardiac RCT; not established

EGCG (green tea)

Fibril-formation inhibitor (polyphenol)

Small observational studies only

Not a recognized drug indication

Imaging surrogate

No; uncontrolled data only

↓ **Table 7.** Therapeutic Strategies for Transthyretin Amyloid Cardiomyopathy
Treatment category	Drugs	Mechanism of action
TTR: transthyretin; siRNA: small interfering RNA; mRNA: messenger RNA; TUDCA: tauroursodeoxycholic acid; CRISPR: clustered regularly interspaced short palindromic repeats.
TTR stabilization	Tafamidis, acoramidis	Stabilize TTR tetramer by binding to thyroxine-binding sites, preventing tetramer dissociation and reducing the rate-limiting step in fibril formation [7, 8, 12]
Gene silencing	Patisiran, vutrisiran, eplontersen	Reduce hepatic TTR synthesis through RNA interference (siRNA) or antisense oligonucleotide mechanisms, inducing degradation of TTR mRNA and achieving profound reductions in serum TTR levels [9, 22, 26]
Fibril disruption	Doxycycline-TUDCA	Disrupt amyloid fibril formation and exert cytoprotective effects (not currently recommended as evidence-based therapy following negative phase 3 trial results) [30]
Amyloid depletion	NI006, PRX004	Remove deposited amyloid via monoclonal antibodies that bind specifically to misfolded or aggregated TTR; antibody-amyloid complexes are recognized and cleared by phagocytic immune cells [36, 37]
Gene editing	NTLA-2001, nexiguran ziclumeran	Permanent TTR gene inactivation using CRISPR-Cas9 in vivo gene editing; single-dose administration creates insertions or deletions in the chromosomal TTR gene, disrupting gene function and producing durable reductions in serum TTR [38, 39]

↓ Table 7. Therapeutic Strategies for Transthyretin Amyloid Cardiomyopathy

Treatment category

Drugs

Mechanism of action

TTR: transthyretin; siRNA: small interfering RNA; mRNA: messenger RNA; TUDCA: tauroursodeoxycholic acid; CRISPR: clustered regularly interspaced short palindromic repeats.

TTR stabilization

Tafamidis, acoramidis

Stabilize TTR tetramer by binding to thyroxine-binding sites, preventing tetramer dissociation and reducing the rate-limiting step in fibril formation [7, 8, 12]

Gene silencing

Patisiran, vutrisiran, eplontersen

Reduce hepatic TTR synthesis through RNA interference (siRNA) or antisense oligonucleotide mechanisms, inducing degradation of TTR mRNA and achieving profound reductions in serum TTR levels [9, 22, 26]

Fibril disruption

Doxycycline-TUDCA

Disrupt amyloid fibril formation and exert cytoprotective effects (not currently recommended as evidence-based therapy following negative phase 3 trial results) [30]

Amyloid depletion

NI006, PRX004

Remove deposited amyloid via monoclonal antibodies that bind specifically to misfolded or aggregated TTR; antibody-amyloid complexes are recognized and cleared by phagocytic immune cells [36, 37]

Gene editing

NTLA-2001, nexiguran ziclumeran

Permanent TTR gene inactivation using CRISPR-Cas9 in vivo gene editing; single-dose administration creates insertions or deletions in the chromosomal TTR gene, disrupting gene function and producing durable reductions in serum TTR [38, 39]