Date: 2014-06-01
Type of
information: Presentation of results at a congress
phase: 2-3
Announcement: presentation of results at the European Atherosclerosis Society (EAS) Meetings in Madrid, Spain
Company: Amgen (USA -CA)
Product: evolocumab (AMG 145)
Action
mechanism:
- monoclonal antibody/RNAi/PCSK9 inhibitor. Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is a protein that targets LDL receptors for degradation and thereby reduces the liver's ability to remove LDL-C, or "bad" cholesterol, from the blood. Evolocumab, being developed by Amgen scientists, is designed to bind to PCSK9 and inhibit PCSK9 from binding to LDL receptors on the liver surface. In the absence of PCSK9, there are more LDL receptors on the surface of the liver to remove LDL-C from the blood.
Disease: familial hypercholesterolemia
Therapeutic
area: Genetic diseases - Cardiovascular diseases - Metabolic diseases
Country:
Trial
details:
- TAUSSIG (Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects wIth Genetic LDL Disorders) is a Phase 2/3 trial designed to evaluate the long-term safety, tolerability and efficacy of evolocumab with an estimated enrollment of 310 patients with severe FH. In the multicenter, open-label, long-term, active treatment-only study, patients with severe FH are randomized to subcutaneous evolocumab 420 mg every two weeks or monthly and assessed for up to five years. The primary endpoint of the study is subject incidence of treatment emergent adverse events (TEAEs). Secondary endpoints include the following, measured from baseline at each scheduled visit: percent change in LDL-C, percent change in non-high-density lipoprotein cholesterol (non-HDL-C), percent change in apolipoprotein B (ApoB), percent change in total cholesterol (TC)/HDL-C ratio, percent change in ApoB/apolipoprotein A1 ratio, percent change in lipoprotein(a) and response rate of subjects with 15 percent or greater reduction in LDL-C.
Adolescent and adult patients were eligible for the study if they participated in a qualifying evolocumab parent study or have a diagnosis of FH. For subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent, LDL-C was >130 mg/dL (3.4 mmol/L) while for subjects with diagnosed CHD or CHD risk equivalent, LDL-C was >100 mg/dL (2.6 mmol/L). Subjects on apheresis did not have a LDL-C entry requirement. Patients on apheresis were initiated with treatment with evolocumab 420 mg every two weeks; all others were initiated with evolocumab 420 mg monthly and could be increased to 420 mg every two weeks based on their clinical response.
- Evolocumab phase III program, PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations), includes 13 trials, with a combined planned enrollment of more than 28,000 patients. The Phase 3 studies will evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2), in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2), as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2), and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia.
- Five studies of evolocumab will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease, DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease, and GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization.
Latest
news:
- • On June 1, 2014, Amgen announced preliminary findings from the Phase 2/3 TAUSSIG study in patients with severe familial hypercholesterolemia (FH), were presented in a Clinical & Late-Breaking Session at the 82nd Congress of the European Atherosclerosis Society (EAS 2014). The preliminary analysis of the ongoing Phase 2/3 TAUSSIG study in five patients with severe FH due to PCSK9 gain-of-function mutations (including two receiving lipid apheresis therapy at baseline) was presented. A total of 12 AEs were reported in four patients on evolocumab. None of the AEs were serious and none resulted in permanent discontinuation of evolocumab. Additionally, the study showed that evolocumab 420 mg subcutaneous every two weeks or monthly for at least 12 weeks reduced mean LDL-C by 67 percent from baseline in five patients. Patients on apheresis were treated with evolocumab 420 mg every two weeks; all others were treated with evolocumab 420 mg monthly and could be increased to 420 mg every two weeks based on their clinical response.
Is
general: Yes
