Vutrisiran: Technetium Scintigraphy
Download PDF
Vutrisiran: Technetium Scintigraphy
The full Prescribing Information for AMVUTTRA® (vutrisiran) is provided here. Alnylam Pharmaceuticals does not recommend the use of its products in any manner that is inconsistent with the approved Prescribing Information. This resource may contain information that is not in the approved Prescribing Information.
If you are seeking additional scientific information related to Alnylam medicines, you may visit the Alnylam US Medical Affairs website at RNAiScience.com.
Summary
In the HELIOS-A study, technetium scintigraphy imaging was conducted in a planned cohort as one of the exploratory endpoints to assess cardiac amyloid involvement.1 Cardiac uptake of 99mTc on scintigraphy imaging at Month 18 was reduced from baseline in the majority of evaluable patients following treatment with vutrisiran.1 During the 18-month treatment period of HELIOS-A, the majority of cardiac AEs in the vutrisiran group were mild or moderate in severity.1,2 |
Clinical Data – Case Reports – Abbreviations – References
HELIOS-A
HELIOS-A was a phase 3, global, randomized, open-label study designed to evaluate the efficacy and safety of vutrisiran in patients with hATTR-PN. Patients were randomized (3:1) to receive either vutrisiran 25 mg every 3 months by subcutaneous injection (n=122) or patisiran 0.3 mg/kg every 3 weeks by IV infusion (as a reference group, n=42) for 18 months. This study used the placebo arm of the APOLLO study as an external control arm (n=77) for the primary endpoint and most other efficacy endpoints. The primary endpoint was the change from baseline in mNIS+7 at 9 months.2
At select sites, technetium scintigraphy was conducted as one of the exploratory endpoints to assess cardiac amyloid involvement at baseline and Month 18. Based on local practice for technetium scintigraphy, either 99mTc-DPD, 99mTc-PYP, or 99mTc-HMDP was used as the tracer.1
Planned Technetium Scintigraphy Cohort
Among 64 patients who received vutrisiran and underwent 99mTc scintigraphy at baseline, 47 patients had evaluable data at baseline and Month 18 for normalized LV total uptake. Of these 47 patients, 25 patients were Perugini grade ≥2 at baseline. Forty-eight patients had evaluable data at baseline and Month 18 for H/CL ratio. Of these 48 patients, 26 patients were Perugini grade ≥2 at baseline. Cardiac uptake of 99mTc on scintigraphy imaging at Month 18 was reduced from baseline in the majority of evaluable patients following treatment with vutrisiran (Figure 1). The clinical significance of this observation is not yet clear.1
Figure 1. Quantitative Assessments of Cardiac 99mTc Uptake at Month 18.1
Abbreviations: 99mTc = technetium; H/CL = heart to contralateral lung; LV = left ventricle; mITT = modified intent-to-treat.
Analysis includes vutrisiran-treated patients from mITT population with evaluable data at baseline and Month 18.
“Reduced” refers to a negative change (<0 increase) from baseline to Month 18. “Increased” refers to a >0 increase from baseline to Month 18.
From Garcia-Pavia et al.1
Among those who underwent 99mTc scintigraphy at baseline, 27 (42.2%), 2 (3.1%), 3 (4.7%), and 32 (50.0%) patients were Perugini grade 0, 1, 2, and 3, respectively. Of these 64 patients, 57 patients had evaluable data for Perugini grading at Month 18. A total of 55 (96.5%) patients with evaluable data were unchanged (n = 39, 68.4%) or experienced a reduction by ≥1 Perugini grade (n = 16, 28.1%) at Month 18, when compared to baseline. Among 30 evaluable patients with Perugini grade ≥2 at baseline who were treated with vutrisiran, the Perugini grade was reduced by ≥1 in 15 (50.0%) patients and remained unchanged in 15 (50.0%) patients at Month 18 (Table 1).1
Table 1. Change from Baseline in Perugini Grade at Month 18.1,a
Perugini Grade at Baseline | Perugini Grade at Month 18, n (%) | |||
0 | 1 | 2 | 3 | |
0 | 24 (42.1) | 1 (1.8) | 0 | 0 |
1 | 1 (1.8) | 0 | 1 (1.8) | 0 |
2 | 0 | 0 | 2 (3.5) | 0 |
3 | 2 (3.5) | 3 (5.3) | 10 (17.5) | 13 (22.8) |
Abbreviations: mITT = modified intent-to-treat.
aAnalysis includes vutrisiran-treated patients from mITT population with evaluable data at baseline and Month 18 (n=57).
Perugini grade is a 0-3 scale, where 0 represents no cardiac uptake of the radiotracer and normal bone uptake, 1 represents cardiac uptake that is less than bone uptake, 2 represents cardiac uptake with a similar intensity to bone uptake, and 3 represents cardiac uptake with attenuated or absent bone uptake.
Pink indicates increased Perugini grade (n=2), light gray indicates no change in Perugini grade (n=39), blue indicates reduced Perugini grade (n=16).
Safety Results
During the 18-month treatment period of HELIOS-A, the majority of AEs and cardiac AEs in the vutrisiran group were mild or moderate in severity.1,2
There were no drug-related discontinuations or deaths. Three patients (2.5%) in the vutrisiran arm discontinued the study due to AEs (2 due to death, 1 due to a non-fatal heart failure event), none of which were considered related to vutrisiran. One death was due to COVID-19 pneumonia, and the other was due to iliac artery occlusion. Two SAEs (dyslipidemia and urinary tract infection) were deemed related to vutrisiran by the Investigators.2
AEs occurring in ≥10% of patients in the vutrisiran arm included fall, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia, and dizziness; all of these AEs, with the exception of arthralgia and pain in extremity, were reported at a similar or lower frequency than in the external placebo arm. ISRs were reported in 5 patients (4.1%) receiving vutrisiran, all of which were mild and transient. Overall, there were no safety concerns regarding liver function tests, hematology, or renal function related to vutrisiran.2
A cardiac safety summary of HELIOS-A at 18 months is presented in Table 2.1
Table 2. HELIOS-A 18-Month Cardiac Safety Summary.1
Variable, n (%) | APOLLO mITT | HELIOS-A mITT | APOLLO Cardiac Subpopulation | HELIOS-A Cardiac Subpopulation |
Placebo (n=77) | Vutrisiran (n=122) | Placebo (n=36) | Vutrisiran (n=40) | |
Cardiac AEsa | 28 (36.4) | 37 (30.3) | 13 (36.1) | 15 (37.5) |
Cardiac SAEsa | 10 (13.0) | 11 (9.0) | 4 (11.1) | 6 (15.0) |
Cardiac arrhythmia AEs | 22 (28.6) | 30 (24.6) | 11 (30.6) | 13 (32.5) |
Supraventricular arrhythmias | 13 (16.9) | 10 (8.2) | 9 (25.0) | 7 (17.5) |
Cardiac conduction disorders | 7 (9.1) | 10 (8.2) | 3 (8.3) | 4 (10.0) |
Ventricular arrhythmias and cardiac arrest | 6 (7.8) | 6 (4.9) | 3 (8.3) | 1 (2.5) |
Rate and rhythm disorders | 0 | 8 (6.6) | 0 | 3 (7.5) |
Cardiac failure AEs | 8 (10.4) | 7 (5.7) | 2 (5.6) | 5 (12.5) |
Abbreviations: AE = adverse event; MedDRA = Medical Dictionary for Regulatory Activities; mITT = modified intent-to-treat; SAE = serious adverse event.
aBased on MedDRA ‘Cardiac Disorders’ System Organ Class.
The following information provides an overview of published case reports regarding the use of technetium scintigraphy in patients treated with vutrisiran. It is not intended to be an all-inclusive list or summary of relevant publications, abstracts, and manuscripts.
Hung Y-H, et al. Use of technetium-99m-pyrophosphate single-photon emission computed tomography/computed tomography in monitoring therapeutic changes of RNA interference therapeutics in patients with hereditary transthyretin amyloid cardiomyopathy. J Formos Med Assoc. 2025;124(4):333-339. doi:10.1016/j.jfma.2024.10.0053
A retrospective analysis of 8 patients enrolled in the phase 3 APOLLO and HELIOS-A studies at National Taiwan University Hospital was conducted to assess changes in 99mTc-PYP SPECT/CT imaging results in patients receiving patisiran (n=6) or vutrisiran (n=2) based on first and second image follow-up.
Cohort A consisted of 4 patients who underwent their first 99mTc-PYP SPECT/CT imaging at the initiation of RNAi therapy, while cohort B consisted of 4 patients who had been receiving RNAi therapy before their first 99mTc-PYP SPECT/CT imaging. Both patients who received vutrisiran were in Cohort A.
The median duration from first to second follow-up 99mTc-PYP SPECT/CT imaging was 727 days (range, 569–1031) for the overall group, 569 days (range, 567–571) for Cohort A, and 1068 days (range, 966–1145) for Cohort B.
Additional information on the treatment outcomes, including the change in visual score, planar H/CL ratio, and volumetric H/L ratio, by both cohorts and in the overall group are provided in the publication. Individual data on the treatment outcomes of the 2 patients who received vutrisiran are not presented.
Smiley DA, et al. Gene silencing therapy in hereditary (variant) transthyretin cardiac amyloidosis: A puzzling case of decreasing pyrophosphate uptake on scintigraphy. Circ Cardiovasc Imaging. 2023;16(8). doi:10.1161/CIRCIMAGING.123.0152434
A case report detailed a 46-year-old male patient diagnosed with hATTR with the Glu89Gln variant. Due to family history, the patient underwent genetic testing at 30 years old and was asymptomatic at the time.
At 37 years old, the patient developed symptoms including cramps in the lower extremities, numbness in the feet, and bilateral hand stiffness. At 39 years old, the patient underwent neurological evaluation as well as cardiac testing. A 99mTc-PYP scan was performed and demonstrated diffuse myocardial uptake, with a Perugini grade of 3 and a H/CL ratio of 1.56. The patient did not have any cardiac symptoms at the time.
The patient was initiated on oral diflunisal 250 mg daily for 4 months. He was subsequently enrolled in the HELIOS-A trial and was transitioned to subcutaneous vutrisiran 25 mg every 3 months. After 17 months of treatment (4 months of diflunisal followed by 13 months of vutrisiran), the patient underwent another 99mTc-PYP scan, which showed Perugini grade 1 uptake.
99mTc = 99mtechnetium; 99mTc-DPD = 99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid; 99mTc‑HMDP = 99mtechnetium-hydroxymethylene diphosphonate; 99mTc-PYP = 99mtechnetium-pyrophosphate; AE = adverse event; hATTR = hereditary transthyretin amyloidosis; hATTR-PN = hereditary transthyretin amyloidosis with polyneuropathy; H/CL = heart to contralateral lung; H/L = heart to lung; ISR = injection site reaction; IV = intravenous; LV = left ventricle; MedDRA = Medical Dictionary for Regulatory Activities; mITT = modified intent‑to-treat; mNIS+7 = modified neuropathy impairment score +7; RNAi = ribonucleic acid interference; SAE = serious adverse event; SPECT/CT = single-photon emission computed tomography/computed tomography; Tc = technetium.
Updated 23 September 2025
|
|
|
MED-ALL-TTRSC02-2300027 3.0 Approved through Sep 2027 |
