Amgen has announced the launch of EVOLVE, a further massive global study in its R&D programme, this time to support Mimpara/Sensipar (cinacalcet) its first-in-class treatment for secondary hyper-parathyroidism (SHPT) in chronic kidney disease.
The US-based biotech company announced the study in Glasgow yesterday at ERA-EDTA, the joint meeting of the European Renal and Dialysis and Transplant Associations.
EVOLVE (evaluation of cinacalcet therapy to lower cardiovascular events) is a Phase III trial looking at cinacalcet versus conventional therapy in chronic kidney disease patients on dialysis, with a primary endpoint of all-cause mortality and cardiovascular morbidity (myocardial infarction, myocardial ischaemia, congestive heart failure and cerebrovascular accident).
The study will recruit close to 4,000 patients from 500 centres in over 30 countries throughout North and Latin America, Australia, Russia and the EU and is expected to run for around four years.
Speaking in Glasgow, Dr William Sheridan, Amgen’s medical affairs vice president, said: “This is going to be a terrific study. It is the largest prospective trial in dialysis patients ever conducted and will show for certain whether cinacalcet can save lives.”
Retrospective post-hoc data from four randomised placebo-controlled trials of the drug in the same patient population already suggest substantial benefits, including fewer hospital admissions for CV events, parathyroidectomy, fractures and improved quality of life.
Amgen believes its treatments for chronic kidney disease - which include Aranesp (darbepoetin alfa) for anaemia in cancer and renal failure - offer ‘unsurpassed clinical benefit’. Close to 2 million patients have now received Aranesp which is also being investigated in two major worldwide endpoint trials, RED-HF and TREAT. The former is investigating time to death in 3,400 heart failure patients with anaemia while TREAT is investigating all-cause mortality and CV events in 4,000 renal disease patients with type 2 diabetes.
Plans $1bn R& D spend
“We are putting our money where our mouths are” said Dr Sheridan, who revealed R&D spending in 2006 is up 42% to $860 million. “Spending will rise to more than $1 billion per year as thousands of patients are involved in trials. The growth rate has been astronomical because of the stage of our pipeline,” he added.
The company also has Phase III trials running for its major investigational products denosumab for osteoporosis and metabolic bone disease and panitumumab, its epidermal growth factor receptor (EGFR) inhibitor therapy for colorectal and other EGFR-expressing cancers.
The company made sales in excess of $12 billion in 2005 including $3.3 billion for its lead-selling drug Aranesp where sales grew 32%.
The growing recognition of the cardiovascular complications of renal disease should drive the worldwide market for Aranesp and Mimpara/Sensipar. In recent years it has become apparent that it is cardiovascular disease complications that kill chronic kidney disease patients, many before they even reach dialysis. Studies have already tried investigating the usual interventions of intensive lipid-lowering and blood pressure reduction to no effect on mortality outcomes in renal disease patients.
Chronic kidney disease is increasing to “epidemic” proportions, according to the ERA-EDTA president Jorge Cannata Andia of University of Central Asturias, Oviedo, Spain.
Speaking yesterday he said EU studies show 30 million Europeans have chronic kidney disease with reduced renal function starting during an asymptomatic phase where damage to the vasculature is already occurring. As renal function declines, cardiovascular mortality increases 3.5-fold.
“Creatinine will be the new cholesterol” he asserted, as doctors seek markers of early disease where intervention to reverse renal dysfunction might show benefit. New treatments are in development for this,
Cinecalcet protects the vasculature because it stops further enlargement of the parathyroid gland in chronic kidney disease and may also shrink hyperplasia that has already occurred. This stops the leaching of calcium from bones and into soft tissues, heart and blood vessels which become calcified, stiff and dysfunctional. Vascular calcification carries a 100-fold higher risk of CV mortality and a 20-fold increase of dying whilst on dialysis, said Dr Cannata Andia. COSMOS, a 5,700 patient study is currently evaluating the full extent of the risk.
Meanwhile recognition of the anaemia element of heart failure will also boost Aranesp. Some 23 million patients worldwide suffer from heart failure of whom 20%-30% have anaemia. Correcting anaemia takes the strain off the heart which needs to work harder to deliver oxygen to tissues where there is a red-cell deficit. If RED-HF is positive, the market for Aranesp could soar.
Cinacalcet has been investigated in Phase II as a treatment for primary hyper-parathyroidism and has an approvable letter from the US Food and Drug Administration (FDA) and the equivalent from the European Medicines Agency (EMEA), said the company’s in-house nephrology expert Dr Preston Klassen. The treatment could prevent the need for surgery to remove the parathyroid in these patients.
From Olwen Glynn Owen in Glasgow