Global, randomized, double-blind, multicenter, placebo-controlled study of 225 patients1-3
Change in mNIS+7, a composite measure of neuropathy impairment, from baseline at 18 months
Key Secondary Endpointb
Select Additional Endpointsb
- Serum TTR
- COMPASS 31
93% of patients treated with ONPATTRO and 62% of patients treated with placebo completed 18 months of the assigned treatment.3
aStudy patients had a diagnosis of hATTR amyloidosis with
polyneuropathy caused by any transthyretin (TTR) variant, had FAP
stage I or II disease, had a Neuropathy Impairment Score (NIS) of
5-130, and were permitted to have previously used tetramer
bEndpoints assessed at 18 months.
10MWT=10-meter walk test; COMPASS 31=Composite Autonomic Symptom Score 31; EQ-5D-5L=EuroQoL 5 Dimensions 5 Levels; FAP=familial amyloid polyneuropathy; mBMI=modified body mass index; mNIS+7=modified Neuropathy Impairment Score + 7; NIS-W=Neuropathy Impairment Score-Weakness; Norfolk QoL-DN=Norfolk Quality of Life-Diabetic Neuropathy; R-ODS=Rasch-built Overall Disability Scale.
When patients completed their participation in the 18-month APOLLO
99%c of eligible patients elected to enter the
global OLE study.2
c186 of 187 patients.
Global study1,2225 patients from 19 countries
Broad age range224 to 83 years old (median 62 years)
Multiple variants2,339 different TTR variants were represented in the study population
Prior treatment253% of patients had previously been treated with tafamidis or diflunisal
Stage 1 polyneuropathy3
(mostly mild sensory, motor, and autonomic neuropathy in lower limbs)
Stage 2 polyneuropathy3
Assistance with ambulation required
(mostly moderate impairment progression to the lower limbs, upper limbs, and trunk)
Important Safety Information and Indication
Important Safety Information
Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO® (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.
To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.
Reduced Serum Vitamin A Levels and Recommended Supplementation
ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.
Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).
The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).
ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
For additional information about ONPATTRO, please see the full Prescribing Information.
1. Adams D, Suhr OB, Dyck PJ, et al. BMC Neurol. 2017;17(1):181.
2. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
3. ONPATTRO Precribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.