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Also known as ALN-TTRSC04
Nucresiran · 2 trials · 3 indications
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.
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.
| Arm | Type | Description |
|---|---|---|
| Nucresiran 300 mg | EXPERIMENTAL | Patients 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 mg | ACTIVE_COMPARATOR | Patients 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 |
| Placebo | PLACEBO_COMPARATOR | Participants 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. |
| Name | Type | Description |
|---|---|---|
| Nucresiran | DRUG | Nucresiran 300 mg administered SC q6M |
| Vutrisiran | DRUG | Vutrisiran 25 mg administered SC q3M |
| Sterile Normal Saline (0.9% NaCl) | DRUG | Sterile Normal Saline (0.9% NaCl) administered SC once q6M |
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...
Nucresiran is an investigational RNA therapy being developed by Alnylam Pharmaceuticals for hereditary transthyretin-mediated amyloidosis with polyneuropathy and for transthyretin amyloidosis with cardiomyopathy. It is a small interfering RNA designed to reduce production of the transthyretin protein. It is currently in Phase 3 clinical development and has not been approved by the FDA.
Nucresiran is being studied for two conditions: hereditary transthyretin-mediated amyloidosis with polyneuropathy, sometimes called hATTR-PN, and transthyretin amyloidosis with cardiomyopathy. Both are rare diseases driven by the transthyretin protein. Nucresiran remains investigational and is not yet approved for any indication.
Nucresiran targets transthyretin, or TTR, the protein that misfolds and deposits as amyloid in these diseases. It belongs to the siRNA class, also reflected in the -siran suffix in its name. By targeting TTR, the therapy aims to lower transthyretin production at the source rather than only stabilizing the circulating protein.
Nucresiran is being developed by Alnylam Pharmaceuticals, Inc., which trades on the Nasdaq under the ticker ALNY. Alnylam is the sponsor of the Phase 3 TRITON-PN and TRITON-CM studies evaluating the drug in polyneuropathy and cardiomyopathy forms of transthyretin amyloidosis.
Nucresiran is in Phase 3 clinical development. It has not been approved by the FDA and remains an investigational therapy. Two Phase 3 trials are currently recruiting: TRITON-PN in hereditary transthyretin amyloidosis with polyneuropathy and TRITON-CM in transthyretin amyloidosis with cardiomyopathy.
Nucresiran is being evaluated in two recruiting Phase 3 trials. NCT07223203, called TRITON-PN, enrolls about 125 adults with hereditary transthyretin amyloidosis with polyneuropathy. NCT07052903, called TRITON-CM, enrolls about 1,750 adults with transthyretin amyloidosis with cardiomyopathy. Both are active-controlled studies in patients aged 18 and older across many countries.