Alirocumab

Additional information

Pharmacokinetics and dosing

No significant sex-related differences in alirocumab pharmacokinetics have been demonstrated, and no sex differentiation in dosing is suggested by the pharmaceutical company [1].

Effects

A post-hoc analysis of pooled phase III clinical trial data for alirocumab (3090 men, 1882 women) was performed with a specific focus on potential sex-related differences in efficacy [2]. The majority of included trials compared alirocumab 75/150 mg q2w versus placebo or ezetimibe in adults with inadequately controlled LDL-C and background therapy with a maximally tolerated statin [2].

Higher baseline LDL-C levels of approximately 3.5 mmol/L in the female subjects vs. approximately 3.1 mmol/L in the male subjects were noted in the pooled populations [2], which is roughly in line with anticipated sex-related differences in this age category. The mean average on-treatment levels of LDL-C with alirocumab were 1.82 mmol/L in the female subjects versus 1.33 mmol/L in the males [2]. Significantly more women (36%, vs. 24% of the men) were subjected to dose increases from 75 mg to 150 mg every two weeks in order to meet prespecified LDL-C targets of 1.8 mmol/L [2]. The results may at least in part have been attributable to differences in baseline characteristics between included men and women [2]. However, higher levels of circulating PCSK9 in women constitute a suggested mechanism behind potential sex-related differences in alirocumab efficacy [3]. The inverse correlation between mmol/L reduction of LDL-C and relative risk of major adverse cardiovascular events did not differ significantly between men and women according to the post-hoc analysis [2]. However, the relatively limited duration of follow-up (≤ 2 years) in the respective clinical trials precludes conclusions regarding potential sex-related differences during long-term treatment.

It is conceivable that effects on other parameters than LDL-C might be of additional relevance for potential sex-related differences in the efficacy and safety of alirocumab. To our knowledge, this has not been demonstrated to date.

Adverse effects

Subgroup analysis of pooled clinical trial data (3090 men, 1882 women) did not show any clinically relevant sex-related differences [2]. The safety profile was similar for the different dose levels of 75 mg and 150 mg respectively, every two weeks [2]. Similar findings were seen in a real-world setting [4].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).