New drug classes showing promise in angina
angina, a chronic condition marked by recurrent episodes of
suffocating chest pain from lack of oxygen to the heart muscle, has
shown encouraging safety and efficacy in a Phase II trial.
The results suggest that Schering of Germany's oral formulation of fasudil, a Rho-kinase inhibitor, could become an important new treatment for stable angina. This debilitating symptom of coronary artery disease affects around 4 per cent of people in developed countries and is associated with significant levels of illness and death.
In addition, the findings usher in Rho-kinases as interesting new drug targets. The proteins are involved into a variety of biochemical signal transductions in the cells. Inhibition of Rho-kinase helps blood vessels to relax and increases the blood supply of cardiac tissue.
Schering is excited by the prospects for fasudil, which it believes has a €300 million potential market in the area of stable angina alone. And other investigations have suggested that Rho-kinase inhibition may also be of benefit in other indications, such as essential hypertension and benign prostatic hypertrophy.
An intravenous formulation of the drug is already sold in Japan for the acute treatment of sub-arachnoid haemorrhage, a form of stroke, but the oral formulation could expand its use into chronic, long-term therapy.
"The data derived so far demonstrate safety and efficacy of the oral formulation of fasudil," said Joachim-Friedrich Kapp, head of specialised therapeutics at Schering. He described fasudil's performance in stable angina as 'unusual, something unique that we do not see with other drugs', adding that it seems to have a complementary action that does not interfere with existing treatments such as beta blockers and short-acting nitrates.
In the placebo-controlled Phase II trial, 41 patients were given fasudil, and 43 patients were given placebo. Treatment with the highest dose of fasudil (80mg three times a day) was most effective and improved exercise time and time to exercise-induced myocardial ischaemia in stable angina patients. Signs of oxygen deprivation were delayed by nearly three minutes (172 seconds) compared to a delay of 44 seconds in the placebo group (p < 0.012).
Fasudil's progress through the clinic is being watched closely by other companies interested in developing Rho-kinase inhibitors for therapeutic applications. One such company, Xcellsyz of the UK, has developed several Rho-kinase inhibitors that are available for licensing.
Schering in-licensed the US and EU marketing rights for the oral and injectable formulations of fasudil from Japan's Asahi Kasei Pharma, and is co-developing the oral formulation of fasudil with the Japanese firm. The oral version is expected to reach the market in 2008.
If only…
Meanwhile, despite there being little change in the arsenal of drugs to treat stable angina over the last years, another drug with a novel mode of action is also progressing through clinical trials.
Towards the end of last year, the results of the INITIATIVE trial showed that Servier's ivabradine, the first selective and specific If inhibitor, was at least as effective as the beta blocker atenolol but did not display any of the side-effects commonly associated with beta blockers, such as sexual dysfunction, asthenia or bronchospasm.
Ivabradine reduces heart rate by specific action on the sino-atrial node. The class gets its name from In for ion and f for 'funny,' because the ion channels the drugs target were first described as 'funny channels' in the literature.
