Biotech Values

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Recent positive Phase III trials

Nature Drug Discovery Oct. 2008

Diabetes - AtheroGenics have announced positive top-line results from the Phase III NDES trial evaluating AGI-1067 (succinobucol) for type 2 diabetes (Table 1).
Succinobucol has both antioxidant and anti-inflammatory properties, suggesting potential for treating diseases in which oxidative stress and inflammation are important, such as cardiovascular disease (CVD) and diabetes. Its potential as a novel diabetes therapy was highlighted in the earlier Phase III ARISE trial, which assessed the effect of succinobucol on cardiovascular outcomes in patients with recent acute coronary syndromes (Lancet 371, 1761–1768; 2008). Although the primary composite end point of this trial was not met, effects on secondary and tertiary end points, including improved glycaemic control and reduced incidence of new-onset diabetes, were noted. The ANDES results reported seem to further support the potential of succinobucol as a diabetes therapy: the primary end point of a significant reduction in glycated haemoglobin A1c levels versus placebo at the end of the study’s 6-month daily oral dosing regimen was met for both doses.
Demonstration of long-term safety — particularly with regards to cardiovascular risk — has recently become a key issue in diabetes drug development. Succinobucol was reported to be well tolerated in the ANDES trial and indeed decreased several cardiovascular secondary end points in Arise. However, “somewhat concerning is the rise in LDL cholesterol and blood pressure seen in Arise, since these are particularly important CVD risk factors in patients with diabetes,” said Professor Vivian fonseca, Chief of endocrinology at Tulane university Health sciences Center, new orleans, usA. “The drug does appear to have some beneficial effects on glucose lowering, although the placebo-subtracted difference observed in ANDES is not large, and there seem to be population differences in the effects. These issues need further clarification before conclusions can be drawn about the place of the drug in the treatment of diabetes.”

HIV-associated lipodystrophy - Long-term Phase III data on tesamorelin (Theratechnologies), which might become the first pharmacotherapy for HIV-associated lipodystrophy, have been published (AIDS 22, 1719–1728; 2008) (Table 1).
HIV-associated lipodystrophy — peripheral subcutaneous lipoatrophy and accumulation of visceral adipose tissue (VAT) — is common in patients receiving antiretroviral therapy for HIV. Accumulation of VAT might represent a cardiovascular risk, as well as having distressing effects on body appearance that could reduce therapy compliance.
The development of tesamorelin, a growth-hormone-releasing hormone analogue that is subcutaneously injected once-daily, is based on evidence that growth hormone axis stimulation can reduce visceral adiposity. results showing a ~20% difference in a measure of VAT after 26 weeks of therapy compared with placebo were published last year (NEJM 357, 2359–2370; 2007). The latest data show that a decrease in VAT is sustained over 52 weeks of treatment. “This appears to be the best tolerated and most potent intervention that has been trialled,” says Andrew Carr, senior staff specialist, HIV, immunology and infectious Diseases unit st Vincent’s Hospital, sydney, Australia. “However, although the drug does reduce fat accumulation, there is not much evidence that it is addressing the underlying pathogenesis of the condition. The data also show that once treatment stops, fat accumulation resumes, which raises questions over the value of treating a possible drug complication with permanent treatment.”