Eplontersen

Eplontersen has not been studied in patients with eGFR <45 mL/min/1.73 m² or end-stage renal disease and should only be used in these patients if the anticipated clinical benefit outweighs the potential risk.

Eplontersen has not been studied in patients with moderate or severe hepatic impairment and should only be used in these patients if the anticipated clinical benefit outweighs the potential risk.

The safety and efficacy of eplontersen have not been evaluated in patients undergoing liver transplant.

No data are available.

There are no data on the use of eplontersen in pregnant women. Animal studies are insufficient with respect to reproductive toxicity. Due to the potential teratogenic risk arising from unbalanced vitamin A levels, eplontersen should not be used during pregnancy and in women of childbearing potential not using contraception. In case of pregnancy, close monitoring of the foetus and vitamin A status should be carried out, especially during the first trimester.

It is unknown whether eplontersen or its metabolites are excreted in human milk. A risk to the breastfed child cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from eplontersen therapy, taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Women of child-bearing potential

Eplontersen will reduce the plasma levels of vitamin A, which is crucial for normal foetal development. It is not known whether vitamin A supplementation will be sufficient to reduce the risk to the foetus. For this reason, pregnancy should be excluded before initiation of eplontersen therapy and women of child-bearing potential should practice effective contraception.

If a woman intends to become pregnant, eplontersen and vitamin A supplementation should be discontinued, and serum vitamin A levels should be monitored and have returned to normal before conception is attempted. Serum vitamin A levels may remain reduced for more than 15 weeks after the last dose of treatment.

Fertility

There is no information available on the effects of eplontersen on human fertility. No impact on male or female fertility was detected in animal studies.

Eplontersen has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most frequent adverse reactions during treatment with eplontersen were vitamin A decreased (97% of patients) and vomiting (9% of patients).

Tabulated list of adverse reactions

The safety data reflects exposure to eplontersen in 144 patients with polyneuropathy caused by ATTRv (ATTRv-PN) randomised to eplontersen and who received at least one dose of eplontersen. 130 patients completed treatment with eplontersen through Week 85. The mean duration of treatment was 541 days (range: 57 to 582 days).

Adverse reactions are organised by MedDRA System Organ Class (SOC). Within each SOC, preferred terms are arranged by decreasing frequency and then by decreasing seriousness. Frequencies of occurrence of adverse reactions are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000) and not known (cannot be estimated from available data).

Adverse reactions reported for eplontersen:

^* Based on laboratory findings of vitamin A below the lower limit of normal during the study.