According to the
"Phase 2 findings from OSLER, the first reported 52-week evaluation of a PCSK9 inhibitor, are encouraging and suggest evolocumab may be a promising option to treat hyperlipidemia in a range of at-risk patients," said
OSLER is an ongoing open-label extension study evaluating the long-term safety and efficacy of evolocumab in patients with high cholesterol. In the first year, patients were randomized 2:1 to receive evolocumab and SOC or SOC alone.
"Many patients with high cholesterol struggle to adequately reduce their LDL-C, a significant contributor to cardiovascular disease," said
Adverse events occurred in 81.4 percent of patients treated with evolocumab and SOC and in 73.1 percent of the SOC group. The five most common AEs in the evolocumab and SOC group compared to the SOC group were nasopharyngitis (12.2 percent vs. 9.8 percent), upper respiratory tract infections (7.7 percent vs. 7.6 percent), influenza (7.1 percent vs. 5.2 percent), arthralgia (6.9 percent vs. 4.3 percent), and back pain (6.5 percent vs. 5.4 percent). Other AEs that were reported included muscle-related events (9.2 percent vs. 9.8 percent), elevated liver function tests (1.8 percent vs. 1.6 percent), and elevated creatine kinase (1.0 percent vs. 1.9 percent) for patients treated with evolocumab and SOC compared to SOC alone, respectively. Serious AEs occurred in 7.1 percent of patients treated with evolocumab and SOC and 6.3 percent of the SOC group.
In the OSLER clinical trial, subcutaneous monthly treatment with evolocumab in combination with SOC resulted in a significant LDL-C decrease versus SOC alone in patients who previously completed one of four 12-week Phase 2 studies of evolocumab. After 52 weeks of treatment, patients who first received evolocumab in the OSLER study experienced an average of 52 percent reduction in LDL-C, as measured by the accepted standard preparative ultracentrifugation compared to baseline of the Phase 2 parent study. Patients who received one of six dosing regimens of evolocumab in the parent studies and received evolocumab and SOC in OSLER had persistent average LDL-C reductions of 50 percent at the end of the parent study vs. 52 percent at 52 weeks. Improvements in lipoprotein(a) and apolipoprotein B were also sustained up to 52 weeks.
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OSLER Study Design
OSLER (Open Label Study of Long TERm Evaluation Against LDL-C Trial) is an open-label extension study to assess the long-term safety and efficacy of evolocumab. Patients who completed any of the four 12-week Phase 2 studies of evolocumab were eligible. The Phase 2 studies included:
– MENDEL (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Patients Currently Not Receiving Drug Therapy for Easing Lipid Levels) in patients who were not receiving statin therapy.
– LAPLACE-TIMI 57 (LDL-C Assessment With P
– RUTHERFORD (RedUction of LDL-C With PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study) in patients with heterozygous familial hypercholesterolemia.
– GAUSS (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) in statin-intolerant patients.
A total of 1,104 patients enrolled in the OSLER extension study. Patients were randomized 2:1 to receive evolocumab subcutaneously at 420 mg monthly with SOC or SOC alone for one year. The primary objective was to evaluate the safety and tolerability of evolocumab on a background of SOC. Secondary objectives were effects on lipid parameters compared to Phase 2 study baseline levels.
The Phase 3 program 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, including the FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) study, which will assess whether treatment with evolocumab compared to placebo reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease.
Additional information about clinical trials of evolocumab can be found at www.clinicaltrials.gov.
Evolocumab is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9).1 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.6 Evolocumab, being developed by
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