Gene silencing therapies might be safe for renal function and were not associated with estimated glomerular filtration rate (eGFR) worsening in hereditary transthyretin amyloidosis (hATTR), according to a new study conducted by researchers from Italy.

Before treatment initiation, the average change in eGFR was 0.01 mL/min/1.73 m2 per month (95% CI, -0.38-0.41) for a cohort taking inotersen (Tegsedi®) and -0.62 mL/min/1.73 m2 per month (95% CI, -1.38-0.14) for a cohort taking patisiran (Onpattro®). During follow-up, the average change in eGFR was -0.23 mL/min/1.73 m2 per month (95% CI, -0.49-0.03) with inotersen and -0.20 mL/min/1.73 m2 per month (95% CI, -0.79-0.39) with patisiran.

The researchers did not find any statistically significant difference in eGFR between treatment groups or intra-group before and after treatment with inotersen or patisiran.

“[The] eGFR slope after starting therapy is similar for both drugs, showing a slow decline that is normal for the elderly, so an effect in preventing renal involvement due to amyloidosis can be supposed,” they said.

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Moreover, researchers observed a trend for attenuating the decline in the patisiran cohort, which confirmed the efficacy of the drug, they explained.

Also, the change in the eGFR of the inotersen cohort mirrored the change in the eGFR of the patisiran cohort, suggesting that the renal complications reported in the NEURO-TTR trial might be rare in real-life experience. Nevertheless, the researchers recommend regular monitoring of renal function in these patients.

The study enrolled 17 patients diagnosed with hATTR and followed at the neurology unit of Fondazione Policlinico Universitario A. Gemelli IRCCS, in Rome, Italy. Most patients had either the Phe64Leu variant (47%) or the Val30Met variant (35%). In addition, 12% of patients had the Thr59Lys variant and 6% had the Ile68Leu variant.

Reference

Luigetti M, Guglielmino V, Romano A, et al. Trajectories of kidney function in patients with ATTRv treated with gene silencers. Genes. 2022;13(12). doi:10.3390/genes13122236