REDEMPLO Solution for injection Ref.[116717] Active ingredients: Plozasiran

Hyperglycaemia

Data suggest that plozasiran may increase blood glucose levels in some patients. Hyperglycaemia occurred in more patients on plozasiran, compared to patients on placebo in the placebo-controlled studies (see section 4.8). Some patients with diabetes or at increased risk of developing diabetes may develop a degree of hyperglycaemia requiring treatment as prescribed for diabetes. These patients should be monitored both clinically and biochemically, in accordance with national guidelines.

Sodium content

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

No clinical interaction studies have been conducted.

Pregnancy

There are no data from the use of plozasiran 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 plozasiran during pregnancy.

Breast-feeding

It is unknown whether plozasiran/metabolites are excreted in human milk. There is no information on the excretion of plozasiran/metabolites in animal milk. A risk to newborns/infants cannot be excluded.

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from plozasiran 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. Plozasiran had no effect on fertility in rats. The collective data from the monkeys and rats indicate that the clinical relevance of the lower reproductive organ weights noted in a subset of the male monkeys is unlikely and the risk for impact to male fertility and reproductive organ development in humans is low (see section 5.3).

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

Summary of the safety profile

The most common adverse reactions are hyperglycaemia (12.8%), headache (6.8%), nausea (4.7%), and injection site reaction (4.7%).

Adverse events leading to discontinuation of treatment were hyperglycaemia (0.7%) and urticaria (0.7%).

Tabulated list of adverse reactions

Table 1 presents the adverse reactions reported in patients treated with 25 mg plozasiran in three placebo-controlled clinical studies (two phase 2 studies in patients with severe hypertriglyceridaemia and moderate hypertriglyceridaemia and one phase 3 study in patients with FCS).

The adverse reactions are listed according to the MedDRA system organ class and by frequency. The frequency categories are 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 the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions:

ALT = alanine aminotransferase; AST = aspartate aminotransferase.
^a See section "Description of selected adverse reactions"

Description of selected adverse reactions

Hyperglycaemia

Hyperglycaemia occurred in 12.8% and 9.8% of plozasiran and placebo patients, respectively, in the placebo-controlled studies. The proportion of patients in each group who discontinued treatment due to hyperglycaemia was 1.4% and 0% in plozasiran and placebo patients, respectively. Hyperglycaemia events in patients treated with plozasiran included blood glucose increased (1.4%), diabetes mellitus (1.4%), glycosylated haemoglobin increased (4.1%), hyperglycaemia (1.4%), and type 2 diabetes mellitus (5.4%) (see section 4.4).

Injection site reaction

Injection site reactions occurred in 4.7% and 1.2% of plozasiran and placebo patients, respectively, in the placebo-controlled studies. All of these adverse reactions were mild in severity. No patients discontinued treatment or required alterations or delays in dosing due to injection site reactions. Injection site reaction events in patients treated with plozasiran included injection site erythema (0.7%), injection site pain (2.7%), and injection site reaction (1.4%). Incidence of injection site reaction events was highest after the first dose and decreased with subsequent doses.

Laboratory observations

Increased hepatic transaminases

In phase 2 and phase 3 clinical studies, there were more frequent elevations > ULN of serum hepatic transaminases in patients on plozasiran than placebo. Asymptomatic transient elevations of ALT and AST >3 x ULN occurred in 1.5% and 0.7%, respectively, of participants treated with plozasiran. These elevations did not progress to exceed the threshold of >5 × ULN and did not require dose adjustment or treatment discontinuation.

LDL-C levels

Treatment with plozasiran may increase low-density lipoprotein cholesterol (LDL-C) levels. In clinical studies, median LDL-C increased from approximately 0.55 mmol/L at baseline to 1.0–1.1 mmol/L by month 10, with levels generally plateauing thereafter.

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.