First-in-class diabetic drug to make market impact
multi-billion-dollar market that is poorly served by existing
drugs. All this is set to change as Palosuran, currently in
clinical development, could become the first drug in a new class
for a condition that may affect as much as 140 million people.
Actelion's Palosuran, a first-in-class urotensin II antagonist, is in development for the treatment of diabetic nephropathy in type 2 diabetic patients. Data from the phase II studies is expected in 2Q 2005.
Diabetes is forecast by the International Diabetes Federation to increase by around 62 per cent by 2025, affecting 60-140 million people, and with a forecast prevalence to increase to 9.1 per cent and 9.7 per cent in Europe and the US over that period, the incidence of diabetic nephropathy, which occurs in 20-50 per cent of type 1 and 2 diabetic patients, is also likely to increase significantly.
The report, compiled by >Goldman Sachs Global Investment Research, have forecasted a launch in 2011 and global sales to peak at $1.5 billion (€1.16 billion) As Actelion is the first company to take a urotensin-II antagonist in to the clinic, it will be the first to find out whether or not this class of drugs has utility in various indications.
The prevalence of type 1 and type 2 diabetes has increased substantially in the last 20 years in the western world and is forecast to continue to grow at an alarming rate. The prevalence of diabetes in the US alone increased at a compound annual growth rate (CAGR) of nearly 4 per cent between 1980 and 2002. However, the growth rate in the last ten years of this period increased to nearly 6 per cent, leading to the number of diagnosed cases of diabetes increasing by 52 per cent from 1997-2003.
Actelion's urotensin-II antagonist palosuran is the most advanced drug in this class currently in development. Actelion has published pre-clinical data indicating that a urotensin-II antagonist could reverse or protect against some of the effects of induced renal damage. However, these studies were conducted in animals and there is no guarantee that a urotensin-II antagonist would play the same role in humans.
Actelion has said little about its phase I study with palosuran. It has published one paper on some pre-clinical data generated with palosuran in the Journal of Pharmacology and Experimental Therapeutics in 2004.
Palosuran is a very potent antagonist of urotensin-II binding to the human urotensin-II receptor. Palosuran appears to inhibit urotensin-II binding by acting at high and low affinity sites on the urotensin-II receptor and inhibition appears to be competitive at both receptor sites (although in short-duration binding studies, antagonism appears to be non-competitive).
Although ACE inhibitors and A-II antagonists have shown efficacy in diabetic nephropathy, only Cozaar (Merck and Co) has a label that reflects this, and none of the trials to date have measured morbidity and mortality as key end-points.
According to Goldman Sachs, only Avosentan (SPP-301, Speedel), which will begin phase III trials before year-end, is a credible candidate in development. As such, with a large and expanding market the competitive environment is relatively benign.
Other therapies being investigated include Novartis' renin inhibitor Aliskerin, currently at the phase II stage of development. Aliskerin is an orally active renin inhibitor in development for the treatment of hypertension. It is being developed by Novartis and re-licensed from Speedel.
Keryx pharmaceuticals GAG replacement candidate KRX-101 is also currently in the phase II/III stage of development. The compound is being tested in diabetic nephropathy patients that are expected to commence before mid-2005. KRX-101 (suledoxide) is a mixture of two glycosaminoglycans: 80 per cent heparin and 20 per cent dermatan sulphate.