TRYNGOLZA Solution for injection Ref.[115924] Active ingredients: Olezarsen

Hypersensitivity reactions

Hypersensitivity reactions (including symptoms of diffuse erythema and chills) have been reported in patients treated with Tryngolza (see section 4.8). If a serious hypersensitivity reaction occurs, Tryngolza must be discontinued immediately and appropriate therapy initiated.

General

Limited safety data exist for olezarsen use in FCS patients at the time of marketing authorisation. While no serious risks of thrombocytopenia, hepatotoxicity, or renal toxicity were identified during clinical development, these adverse reactions have been observed with some antisense oligonucleotides and cannot be completely excluded.

Use in patients with low platelet counts

Some patients with FCS are susceptible to platelet count variability over time as part of the natural history and progression of the disease. There are limited data available on the use of olezarsen in FCS patients with platelet count <100 000/mm³.

Excipient with known effect

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per 80 mg dose, that is to say essentially 'sodium-free'.

No interaction studies have been performed.

In vitro studies show that olezarsen is not a substrate or inhibitor of transporters, does not interact with highly plasma protein bound medicines, and is not an inhibitor or inducer of cytochrome P450 (CYP) enzymes. Oligonucleotide therapeutics, including olezarsen, are not typically substrates of CYP enzymes. Therefore, olezarsen is not expected to cause or be affected by interactions mediated through transporters, plasma protein binding or CYP enzymes.

Tryngolza can be used with other lipid-lowering medicines, for example statins and fibrates.

Pregnancy

There are no data from the use of olezarsen in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of Tryngolza during pregnancy and women of child-bearing potential should practice effective contraception.

Breast-feeding

There is no information on the excretion of olezarsen/metabolites in human milk, the effects of olezarsen on breastfed newborns/infants, or the effects of olezarsen on milk production in treated women (see section 5.3).

The unconjugated antisense oligonucleotide (ASO), which shares the same nucleotide sequence but lacks N-acetylgalactosamine (GalNAc), was present in the milk of lactating mice at very low levels. Oligonucleotide-based products typically have poor oral bioavailability. Due to the poor oral bioavailability of this medicinal product, it is considered unlikely that low levels present in human milk will lead to clinically relevant levels in breastfed newborns/infants.

A risk to the newborns/infants cannot be excluded.

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

Fertility

No clinical data on the effect of this medicinal product on human fertility are available.

No adverse effects of olezarsen on fertility were seen in mice (see section 5.3).

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

Summary of the safety profile

In patients with FCS, the most commonly reported adverse reactions during treatment with olezarsen were injection site erythema (17%), headache (16%), arthralgia (15%), and vomiting (10%).

Tabulated list of adverse reactions

The safety data described below reflects exposure to olezarsen in 89 patients with FCS in clinical trials who received at least one dose of olezarsen. Of these, 77 patients received at least 6 months of treatment and 65 patients received at least 12 months of treatment. The mean duration of treatment for these patients was 521 days (range: 28 to 1 080 days).

Adverse reactions are listed according to MedDRA system organ class. The frequency of adverse reactions is defined using the following convention: 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). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 1. Adverse reactions:

Description of selected adverse reactions

Hypersensitivity

Hypersensitivity has been observed with olezarsen. Severe hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills, and myalgias) have been observed in 2 patients in clinical trials. In both patients the event was acute, required treatment, and resulted in treatment discontinuation.

Injection site reactions

Injection site reactions occurred in olezarsen-treated patients with FCS. These local reactions were mostly mild and consisted of injection site erythema (17%), discolouration (9%), pain (6%), and swelling (5%). These events are either self-limiting or can usually be managed using symptomatic treatment.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.