Date: 2014-10-01
Type of
information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in the Lancet
Company: Amgen (USA - CA)
Product: evolocumab
Action
mechanism:
- monoclonal antibody/RNAi/PCSK9 inhibitor. Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove LDL-C from the blood.
Disease: homozygous familial hypercholesterolemia
Therapeutic
area: Rare diseases - Cardiovascular diseases
Country:
Trial
details:
- TESLA was a two-part Phase 2/3 trial evaluating evolocumab in patients with homozygous familial hypercholesterolemia (HoFH), a rare and serious genetic disorder characterized by severely elevated LDL-C at an early age.2 The Phase 3 TESLA trial evaluated the safety, tolerability and efficacy of evolocumab compared to placebo in 49 adult and adolescent (12 to less than 18 years of age) patients with HoFH who were on a stable dose of statin therapy and other lipid-lowering medication. Patients were randomized to evolocumab 420 mg subcutaneous monthly or placebo subcutaneous monthly.
- PROFICIO (Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations), is a large and comprehensive clinical trial program evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.
- The Phase 3 program includes 14 trials to evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2 and YUKAWA-2); in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2 and GAUSS-3); as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2); in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2 and TAUSSIG) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia; as well as the administration of evolocumab (THOMAS-1 and THOMAS-2). Five studies in the evolocumab Phase 3 program 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; OSLER-2 (Open Label Study of Long TERm Evaluation Against LDL-C Trial-2) in patients with high cholesterol who completed any of the Phase 3 studies; 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; and TAUSSIG (Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects with Genetic LDL Disorders), which will assess the long-term safety and efficacy of evolocumab on LDL-C in patients with severe familial hypercholesterolemia.
Latest
news:
- • On October 1, 2014, Amgen announced The Lancet published data from two Phase 3 studies, RUTHERFORD-2 and TESLA, that showed treatment with evolocumab resulted in a statistically significant reduction in LDL-C compared to placebo in patients with different types of familial hypercholesterolemia (FH). The TESLA study evaluating 49 patients with homozygous FH (HoFH), not on apheresis, showed that adding evolocumab 420 mg subcutaneous monthly to a stable dose of statin therapy and other lipid-lowering medications significantly reduced LDL-C by 31 percent (95 percent CI, -44, -18, p<0.001) from baseline at week 12 compared to placebo. In patients with at least one defective LDL receptor mutation, evolocumab reduced LDL-C by 41 percent (95 percent CI, -53, -28, p<0.0001) compared to placebo. The most common AEs (more than one subject) in evolocumab-treated patients were upper respiratory tract infection, influenza, gastroenteritis and nasopharyngitis. Results from the TESLA study were initially presented at the 82nd Congress of the European Atherosclerosis Society (EAS 2014) in June 2014 (See below).
- • On June 1, 2014, Amgen announced new detailed data from the Phase 3 TESLA study evaluating its novel investigational cholesterol-lowering medication, evolocumab (AMG 145), in patients with homozygous familial hypercholesterolemia (HoFH), a rare and serious genetic disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, and premature cardiovascular disease. Phase 3 data from the TESLA study showed that adding evolocumab 420 mg subcutaneous monthly to a stable dose of statin therapy and other lipid-lowering medications significantly reduced LDL-C by 31 percent (p<0.001) from baseline at week 12 compared to placebo. Results from the TESLA study, along with 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). In the Phase 3 TESLA study in 49 HoFH patients, the most common adverse events (AEs), (more than one subject), in the evolocumab group were upper respiratory tract infection (three patients on evolocumab; one patient on placebo), influenza (three patients on evolocumab; 0 patients on placebo), gastroenteritis (two patients on evolocumab; 0 patients on placebo) and nasopharyngitis (two patients on evolocumab; 0 patients on placebo).
- • On March 17, 2014, Amgen has announced that the Phase 3 TESLA (TrialEvaluating PCSK9 Antibody in Subjects with LDL Receptor Abnormalities) trial evaluating evolocumab met its primary endpoint of the percent reduction from baseline at week 12 in low-density lipoprotein cholesterol (LDL-C). The percent reduction in LDL-C, or "bad" cholesterol, was clinically meaningful and statistically significant. Safety was generally balanced across treatment groups. The most common adverse events in the evolocumab group (more than one subject) were upper respiratory tract infection, influenza, gastroenteritis and nasopharyngitis.
- The Phase 3 12-week, double-blind, randomized, placebo-controlled, multicenter part of the TESLA trial evaluated evolocumab in 49 patients with HoFH (LDL-C >130 mg/dL) who were on a stable dose of statin therapy and lipid-lowering medication. Patients were randomized to evolocumab 420 mg subcutaneous monthly or placebo subcutaneous monthly. The primary endpoint was the percent reduction from baseline in LDL-C at week 12. Secondary endpoints included mean percent change from baseline in LDL-C, apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) at weeks 6 and 12, and percent change from baseline in ApoB and Lp(a) at week 12.
Is
general: Yes
