Basel, 05 November 2012
Roche`s aleglitazar renal safety study AleNephro meets primary endpoint
Study was designed to assess whether the effect of aleglitazar on renal function was reversible and comparable to pioglitazone
Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced data from the Phase II AleNephro study which showed that in patients with moderate renal impairment (stage 3 chronic kidney disease) who have type 2 diabetes, the average decrease in renal function observed during treatment with aleglitazar is reversible, mild and stabilises over time. Side effects seen in the study were consistent with previous findings. These data were presented at the annual American Society of Nephrology (ASN) conference in San Diego.
The results showed that after 52 weeks of treatment with aleglitazar and 8 weeks follow up after stopping treatment, the average decline in renal function (eGFR, estimated glomerular filtration rate level) was comparable for patients who had received aleglitazar (-2.7%) versus pioglitazone (-3.4%). The average on-treatment change in eGFR with aleglitazar was -15.0%, compared to -5.4% with pioglitazone. The size of the average on-treatment change in eGFR with aleglitazar in AleNephro is comparable to that seen with ACE-inhibitors and Angiotensin Receptor Blockers (ARBs)1. The AleNephro results also confirm findings from earlier studies which showed aleglitazar improves multiple cardiometabolic risk factors including lipids and glucose control.
“The outcome of AleNephro is an important milestone supporting the development of aleglitazar,” said Hal Barron, M.D., Head of Global Product Development and Chief Medical Officer for Roche. “These data provide reassurance on the renal safety profile of aleglitazar, and bring us a step closer to providing an innovative treatment to patients that aims to reduce the risk of heart attacks, strokes and premature death from cardiovascular disease and type 2 diabetes.”
Cardiovascular medicines ACE-inhibitors and ARBs can also cause a reversible decrease in kidney function, although studies indicate these medicines are protective for the kidneys2, lowering pressure inside the kidneys and reducing the amount of protein in the urine. Along with showing a similar reversible decrease in eGFR, AleNephro showed that aleglitazar reduced protein in the urine by 54% by the end of the follow-up period in patients already receiving ACE-inhibitors or ARBs and who had high levels of protein in the urine (macroalbuminuria) at the beginning of the study.
AleNephro is a multicentre, double-blind Phase IIb randomised trial that investigated the effects of aleglitazar 150 µg on renal function in patients with type 2 diabetes and moderate renal impairment (stage 3 chronic kidney disease), compared to pioglitazone (based on assessment of eGFR levels). 302 patients were randomised to receive either 150 µg/d aleglitazar added to standard of care (SOC) for type 2 diabetes and chronic kidney disease, or 45mg/d pioglitazone added to SOC for 52 weeks, followed by 8 weeks off-treatment follow-up. The primary endpoint assessed the percentage change in eGFR levels from baseline to the end of the follow-up period (i.e. reversibility of change in eGFR).
Aleglitazar is a PPAR-α/γ agonist being investigated as a treatment to reduce major cardiovascular events (cardiovascular mortality, heart attack, or stroke) in patients who have experienced an acute coronary syndrome and have type 2 diabetes or patients with stable cardiovascular disease and type 2 diabetes/pre-diabetes. Aleglitazar is also being investigated as a general type 2 diabetes glucose regulator. Despite currently available medicines, patients who have experienced an acute coronary syndrome or have stable cardiovascular disease and type 2 diabetes/pre-diabetes are at high risk for life-threatening cardiovascular events. There is therefore a significant unmet need among these patients for new effective and well-tolerated treatments that can further reduce cardiovascular risk.
Aleglitazar is being evaluated as part of a comprehensive clinical programme, including the completed phase II studies SESTA-R, SYNCHRONY and AleNephro as well as the Phase III studies AleCardio, AlePrevent and AleGlucose. AleCardio, a large, long-term, event-driven phase III outcomes study, is underway to evaluate whether aleglitazar may reduce major cardiovascular events (cardiovascular mortality, heart attacks, or stroke) in patients who have experienced an acute coronary syndrome and have type 2 diabetes. AlePrevent is a second cardiovascular outcomes trial in patients with stable cardiovascular disease and type 2 diabetes or pre-diabetes, and AleGlucose is a set of glycaemic control trials to further characterise the impact of aleglitazar on glycaemic control in patients with type 2 diabetes.
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalized healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2011, Roche had over 80,000 employees worldwide and invested over 8 billion Swiss francs in R&D. The Group posted sales of 42.5 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.
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1) Bakris GL et al. Arch Intern Med. 2000;160(5):685-93
2) De Zeeuw D et al. Kidney Int. 2004;65(6):2309-20.