Evinocumab (REGN1500) for HoFH and HeFH:
In small HoFH-P2, it did fire (38-45% reduction, range spread is high) bit better than Inclisiran and Repatha/Praluent, on top of LLT.
atherosclerosis-journal.com
<Aim: Carriers of homozygous inactivating mutations in the gene encoding Angiopoietin-like protein 3 (ANGPTL3) have >50% lower LDL-C, HDL-C and triglycerides compared to controls. Moreover, ANGPTL3 inhibition in a LDL-R -/- mouse lowers LDL-C levels. We therefore investigated the efficacy and safety of evinacumab, a human mAb inhibitor of ANGPTL3, in homozygous familial hypercholesterolemia (HoFH) patients on background lipid lowering therapy (LLT).
Methods: Nine molecular-defined HoFH patients (8 on background LLT) were enrolled. Evinacumab was dosed as 250 mg SC injection at baseline and at week-2 as 15 mg/kg IV. Two patients also received 450 mg SC at weeks-12, 13, 14, and 15. The primary endpoint was mean percent change in LDL-C levels from baseline to week-4.
Results: Mean baseline LDL-C was 376.0 mg/dL (SD=240.9 mg/dL). Evinacumab decreased LDL-C (mean=49.2%, SD=23.2%), apolipoprotein B (mean=45.9%, SD=18.2%) and total cholesterol (mean=47%, SD=19%) at week-4. Mean baseline triglycerides were 79.9 mg/dL (SD=41.1 mg/dL); mean reduction at week-4 was 46.5% (SD=17.1%). Mean baseline HDL-C was 38.8 mg/dL (SD=14.3 mg/dL); mean reduction at week-4 was 35.5% (SD=16%). Among the 3 null/null LDLR-mutation carriers (mean baseline 597.8 mg/dL, SD=248 mg/dL), mean LDL-C reduction at week-4 was 37.3% (SD=10%). One serious adverse event occurred (worsening coronary artery disease; not treatment related); there were no adverse events leading to discontinuations. Most common drug-related events were injection-site reaction and hot flush (mild; resolved without treatment).
Conclusions: These preliminary results show a pronounced effect of evinacumab added to LLT in lowering LDL-C in HoFH patients, regardless of genotype.>
Bit of concern is HDLc reduction, but it is not at alarmanting level.
https://clinicaltrials.gov/ct2/show/NCT03409744?term=regeneron&phase=2&rank=3
So, 4 years treatment duration P3 study is long shot, but indicate that subject will be on drug/schedule, in absence of any other better options. |
