Drug products: Praluent
ATC code: C10AX14
In the pivotal clinical trials, women derived smaller mean reductions in LDL-cholesterol (LDL-C) levels than men during treatment with alirocumab. More women than men were subjected to dose increases of alirocumab in attempts to achieve predefined LDL-C targets. No significant sex-related differences in relative risk reduction of cardiovascular events were evident during the limited follow-up period of 72 weeks. No sex-related differences in safety were reported, and the safety profile was similar for the different dose levels of 75 mg and 150 mg respectively, every two weeks.
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 .
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 . 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 .
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 , 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 . 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 . The results may at least in part have been attributable to differences in baseline characteristics between included men and women . However, higher levels of circulating PCSK9 in women constitute a suggested mechanism behind potential sex-related differences in alirocumab efficacy . 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 . 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.
Subgroup analysis of pooled clinical trial data (3090 men, 1882 women) did not show any clinically relevant sex-related differences . The safety profile was similar for the different dose levels of 75 mg and 150 mg respectively, every two weeks . Similar findings were seen in a real-world setting .
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2020-05-25
- Praluent (alirocumab). Summary of Product Characteristics. European Medicines Agency (EMA) [updated 2019-12-05, cited 2020-05-25]
- Vallejo-Vaz AJ , Ginsberg HN, Davidson MH, Eckel RH , Cannon CP , Lee LV, Bessac L, Pordy R, Letierce A, Ray KK. Lower On-Treatment Low-Density Lipoprotein Cholesterol and Major Adverse Cardiovascular Events in Women and Men: Pooled Analysis of 10 ODYSSEY Phase 3 Alirocumab Trials. J Am Heart Assoc. 2018;7(18):e009221. PubMed
- Nicolas X, Djebli N, Rauch C, Brunet A, Hurbin F, Martinez JM et al. Population Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II. Clin Pharmacokinet. 2019;58(1):115-130. PubMed
- Gürgöze MT, Muller-Hansma AHG, Schreuder MM, Galema-Boers AMH, Boersma E, Roeters van Lennep JE. Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience. Clin Pharmacol Ther. 2019;105(2):496-504. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk
Reviewed by: Diana Rydberg, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson