When Amgen (AMGN) develops a drug, the wise King does whatever it takes to squeeze every drop of its therapeutic capability before submitting the new drug application (NDA) to the FDA for approval. The firm is rich in its science, scientists, pipeline of investigational products and its approved products. All the problems the firm encountered that analysts believed would erode its fortune, such as limiting the use of its growth factors did not impact the firm’s growth, but unveiled the character and culture that made the king deserve its throne.
A best example was provided in the various clinical trials Amgen is conducting on its monoclonal antibody drug Evolocumab that targets and inhibits the proprotein convertase subtilisin/kexin type 9 (PCSK9) for the treatment of high cholesterol and the management of coronary heart diseases. The trials are many and are designed to prove the effect of the drug on LDL cholesterol, the time required for the drug to lower this bad cholesterol – the percent reduction from baseline in low-density lipoprotein (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. These were the co-primary endpoints that were met in the MENDEL-2 phase 3 trials whose results were announced this week.
The secondary efficacy endpoints included the absolute change from baseline in LDL-C at week 12 and the percentage changes from baseline at week 12 in the following: Non-high-density lipoprotein cholesterol (non-HDL-C),; apolipoprotein B (ApoB); total cholesterol (TC)/HDL-C; ApoB/apolipoprotein A1 (ApoA1) ratio; lipoprotein(a); triglycerides; HDL-C and very low density lipoprotein (VLDL-C).
The data demonstrate that the mean percent reductions in LDL-C, compared to placebo and ezetimibe were consistent with results observed in the MENDEL Phase 2 study.
The MENDEL-2 phase 3 trial:
Design: MENDEL-2 is a Phase 3 randomized, multi-center, double-blind, double-dummy, stratified, placebo and ezetimibe-controlled parallel group study designed to evaluate the efficacy and safety of evolocumab in hyperlipidemic patients with a 10-year Framingham risk score of 10 percent or less who were not receiving lipid-lowering therapy.
This trial involved 614 patients with high serum level of (LDL-C ≥ 100 mg/dL and < 190 mg/dL) who were not receiving lipid-lowering therapy. Patients were randomized to one of six treatment groups to compare two dosing regimens of evolocumab (140 mg every two weeks or 420 mg monthly) with placebo and ezetimibe (10 mg daily).
Adverse events (AEs): Headache, diarrhea, nausea and urinary tract infection most common in the evolocumab combined group.
The market: HUGE. According to the Centers for Disease Control and Prevention, more than 71 million American adults have high LDL-C.2 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.
PROFICIO, which stands for the 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. Phase 3 clinical trials are currently underway and build upon the Phase 2 studies. The program includes 13 trials, with more than 28,000 patients.
Nothing is left behind in Phase 3 studies that 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 include:
FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether evolocumab + statin vs. placebo + statin reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease,
GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound): To determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization.
Is there anything left in the subject of cholesterol for the FDA or any other agency to ask for?
Nothing is left behind. Nothing will be questioned after the complete announcement of the results, no uncertainty will exist in the minds of physicians. When specialists will prescribe Evolocumab for a special indication, for example coronary artery disease, they will be, indeed, practicing evidence-based medicine.
That’s what Amgen provides. That’s why Amgen is still the King.
We long AMGN
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