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Nucresiran

Phase 3

Hereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy | Small molecule | Rare Disease |Alnylam Pharmaceuticals, Inc.|Last Updated: Aug 14, 2026

Success Probability

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Trial Design

RandomizedACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment125

FDA Designations

No designations recorded

Clinical trial landscape

Nucresiran · 2 trials · 3 indications

Phase 3 2
NCT07223203TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With PolyneuropathyHereditary Transthyretin-Mediated Amyloidosis With Polyneuropathy
RECRUITING125 Analytics
NCT07052903TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With CardiomyopathyTransthyretin Amyloidosis With Cardiomyopathy
RECRUITING1,750 Analytics
PHASE3RECRUITING
TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy
Hereditary Transthyretin-Mediated Amyloidosis With PolyneuropathyUnlock trial analytics
PHASE3RECRUITING
TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Transthyretin Amyloidosis With CardiomyopathyUnlock trial analytics

Study Endpoints

Primary Endpoints

Change from Baseline in the Modified Neuropathy Impairment Score +7 (mNIS+7) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9
Baseline and Month 9

The mNIS+7 is a composite score that measures neurologic impairment which includes the following components: physical exam of lower limbs, upper limbs and cranial nerves to assess motor strength/weakness and deep tendon reflexes, electrophysiologic measurement of large nerve fiber function, sensory testing and postural blood pressure. The mNIS+7 is scored from 0 (no impairment) to 304 points (maximum impairment). A higher score indicates a worse outcome.

Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits)
Baseline to end of double-blind period (estimated 32 months, maximum 5 years)

All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.

Secondary Endpoints

Change from Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9
Baseline and Month 9
Percent Reduction in Serum TTR Levels in the Nucresiran Group Compared to the In-study Vutrisiran Group through Month 9
Up to Month 9
Change from Baseline in Modified Body Mass Index (mBMI) Compared to the External Placebo Group from the APOLLO Study (NCT01960348) at Month 9
Baseline and Month 9
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Nucresiran 300 mgEXPERIMENTALPatients will be administered nucresiran 300 mg subcutaneously (SC) once every 6 months (q6M) during the Treatment Period and Treatment Extension Period
Vutrisiran 25 mg followed by Nucresiran 300 mgACTIVE_COMPARATORPatients will be administered vutrisiran 25 mg SC every 3 months (q3M) during the Treatment Period followed by nucresiran 300 mg SC q6M during the Treatment Extension Period
PlaceboPLACEBO_COMPARATORParticipants will receive placebo administered subcutaneously (SC) once every 6 months (q6M) during the double-blind (DB) period, followed by nucresiran 300 mg administered SC q6M during the open-label extension (OLE) period.

Interventions

NameTypeDescription
NucresiranDRUGNucresiran 300 mg administered SC q6M
VutrisiranDRUGVutrisiran 25 mg administered SC q3M
Sterile Normal Saline (0.9% NaCl)DRUGSterile Normal Saline (0.9% NaCl) administered SC once q6M
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Eligibility Criteria

Age Range18 Years to 85 Years
SexALL
Healthy VolunteersNo
Study Sites48

Inclusion Criteria: * Has documented diagnosis of hATTR-PN * Has a diagnosis of hATTR amyloidosis with polyneuropathy with a documented TTR gene variant * Has a neuropathy impairment score (NIS) of 5 to 130 (inclusive) * Has a Karnofsky Performance Status (KPS) of ≥60% Exclusion Criteria: * Has h...

Countries:United StatesAustraliaBrazilCanadaCyprusFranceGermanyGreeceItalyJapanMalaysiaPortugalSouth KoreaSpainSwedenTaiwanTurkey (Türkiye)ArgentinaAustriaBelgiumChileChinaCzechiaDenmarkHong KongHungaryIrelandIsraelNetherlandsNew ZealandNorwayPolandRomaniaSlovakiaSwitzerlandUnited Kingdom
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Recent Changes (Last 90 Days)

LOWAug 14, 2026NCT07052903lastUpdatePostDate: changed
LOWAug 14, 2026NCT07223203lastUpdatePostDate: changed
LOWAug 14, 2026NCT07052903lastUpdatePostDate: changed
LOWAug 14, 2026NCT07223203lastUpdatePostDate: changed
LOWJul 24, 2026NCT07052903Enrollment: 1250 → 1750
LOWJul 24, 2026NCT07223203lastUpdatePostDate: changed
LOWJul 24, 2026NCT07052903Enrollment: 1250 → 1750
LOWJul 24, 2026NCT07223203lastUpdatePostDate: changed
LOWJun 12, 2026NCT07052903lastUpdatePostDate: changed
LOWJun 12, 2026NCT07223203lastUpdatePostDate: changed
LOWJun 12, 2026NCT07052903lastUpdatePostDate: changed
LOWJun 12, 2026NCT07223203lastUpdatePostDate: changed

Frequently asked questions about Nucresiran

What is Nucresiran used for?

Nucresiran is an investigational small molecule being developed for the treatment of transthyretin amyloidosis with cardiomyopathy and hereditary transthyretin-mediated amyloidosis with polyneuropathy. It is currently in Phase 3 clinical development and is not yet approved by regulatory authorities.

What does Nucresiran target?

Nucresiran is a small interfering RNA (siRNA) therapeutic. It is designed to target and silence the transthyretin gene, reducing the production of transthyretin protein, which is the underlying cause of transthyretin amyloidosis.

Who is developing Nucresiran?

Nucresiran is being developed by Alnylam Pharmaceuticals, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol ALNY. Alnylam is conducting the Phase 3 clinical trials for this investigational drug.

What phase is Nucresiran in?

Nucresiran is in Phase 3 clinical development. It is being evaluated in two Phase 3 trials, TRITON-CM and TRITON-PN, which are currently recruiting participants. Nucresiran is an investigational drug and has not received FDA approval.

What clinical trials is Nucresiran in?

Nucresiran is being studied in two Phase 3 trials. The TRITON-CM trial (NCT07052903) evaluates the drug in patients with transthyretin amyloidosis with cardiomyopathy, with an enrollment of 1,750 participants. The TRITON-PN trial (NCT07223203) evaluates it in hereditary transthyretin amyloidosis with polyneuropathy, with 125 participants.

Is Nucresiran the same as other transthyretin amyloidosis drugs?

Nucresiran is a distinct investigational siRNA therapeutic developed by Alnylam Pharmaceuticals. It is not the same as other approved transthyretin amyloidosis treatments, as it is a novel agent currently in Phase 3 trials and has not yet been approved for any indication.