New Medicines

Transthyretin-mediated amyloidosis (ATTR)


New molecular entity
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Sep 21Alnylam submits Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for vutrisiran for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis in adult patients with polyneuropathy. [5]
Jun 21US FDA accepts NDA for treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults with once-quarterly SC vutrisiran with a PDUFA of 14/4/22; Alnylam plan to submit a MAA to EU in 2021 [4].
Jan 21Alnylam plan to file for FDA approval in 2021 but will hold off filing in EU until 18-month data is available (due late 2021) [3].
Apr 20Granted fast track status for treating polyneuropathy of hATTR amyloidosis in adults. Already designated as an orphan drug in US and EU for ATTR amyloidosis [1].


Systemically delivered RNA interference therapy
Transthyretin-mediated amyloidosis = hereditary, systemic disease due to TTR gene mutations. Most TTR protein liver-produced. Mutations cause abnormal amyloid proteins to accumulate & damage body organs /tissues, causing intractable peripheral sensory and autonomic neuropathy, and/or cardiomyopathy. Familial Amyloidotic Polyneuropathy affects ~10,000 pple worldwide + Familial Amyloidotic Cardiomyopathy affects at least 40,000 pple worldwide. Mean life expectanctancy is 5-15yrs [2].
Transthyretin-mediated amyloidosis (ATTR)

Trial or other data

Oct 21Alnylam announce vutrisiran in PIII HELIOS-A met all secondary endpoints measured at 18 months including statistically significant improvements in neuropathy as measured by the modified Neuropathy Impairment Score, quality of life, gait speed, nutritional status and overall disability, relative to external placebo data from the APOLLO Phase 3 study of patisiran. A safe and tolerable profile was demonstrated [6]
Jan 21Alnylam announce that PIII HELIOS-A (n=164) trial has met its primary endpoint. Vutrisiran outperformed Onpattro in terms of change in modified Neuropathy Impairment Score at nine months. The trial also met secondary endpoints that compared the effect of vutrisiran on quality of life and gait speed to the control. The p-values for all three endpoints were less than 0.001. Full data is planed to be shared imminently [3].
Jan 21HELIOS-B (n~600) primary endpoint will evaluate the efficacy of vutrisiran versus placebo for the composite outcome of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent heart failure (HF) visits) at 30-36 months. Secondary endpoints include the change from baseline in the 6-minute walk test (6-MWT), health status measured using the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQOS), echocardiographic assessments of mean left ventricular wall thickness and global longitudinal strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP) as a cardiac biomarker, and all-cause mortality, rate of recurrent CV events, and composite of all-cause mortality and recurrent all-cause hospitalizations and urgent HF visits at month 30 or 30-36 months [1].
Jan 21HELIOS-A (n=164) primary endpoint is change from baseline in the modified Neuropathy Impairment Score +7 (mNIS +7) score at 9 months. Secondary endpoints at 9 months include the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) Total Score and the 10-Meter Walk Test (10-MWT) [1].
Jan 21The safety and efficacy of vutrisiran, SC every three months, are being evaluated in the HELIOS Phase 3 clinical program, currently consisting og two PIII clinical trials: HELIOS-A (NCT03759379) and HELIOS-B (NCT04153149) [1].