No go for Novo's potential stroke therapy

A Phase III clinical trial of coagulation therapy NovoSeven showed that although the drug reduced the amount of bleeding in the brains of patients suffering from intracerebral haemorrhage, or ICH, it didn't reduce the risk of disability or death in the longer term. Over 850,000 people suffer from a stroke each year in the US and UK and it is the single largest cause of adult disability in the developed world. Characterised by restricted blood flow to an area of the brain, strokes are either caused by a blood clot (ischaemic stroke) or when a blood vessel bursts. Although this type of haemorrhagic stroke only accounts for about 15 per cent of all strokes, it are responsible for more than 30 per cent of all stroke deaths, according to the US National Stroke Association. It was hoped NovoSeven could reduce bleeding, referred to as haematoma, specifically within the brain - as opposed to subarachnoid haemorrhages where bleeding occurs around the brain. The drug is an activated, recombinant form of the coagulant protein Factor VIIa, which causes blood clots to grow at the site of an injury to prevent dangerous levels of bleeding. It is already approved for several uses, including reducing bleeding in haemophilia sufferers and during surgery. In the trial, over 800 patients in 22 countries who had suffered spontaneous ICH had their normal treatment supplemented with either NovoSeven or placebo. Although there were some noticeable improvements 15 days after bleeding, Novo said that: "mortality and severe disability was not improved at the end of the study period,"​ and so the company, "has decided not to seek regulatory approval for NovoSeven in ICH."​ Although Novo CEO, Lars Sorensen, described the results as "disappointing," the company are still pursuing NovoSeven as a treatment in other indications. "The results validate the notion that disability increases with the size of the haematoma,"​ said Novo's chief science officer Mads Thomsen. "Beyond doubt, by stopping haematoma growth, NovoSeven has done what it is expected to do but the significant effect...must have been overshadowed by other factors contributing to the final outcome. What these factors are, we currently do not know,"​ he continued. Thomsen went on to say that the patients receiving placebo treatment had better clinical results than in the preceding trials. He said: "Breakthrough bleeding into the hollow spaces of the brain, by chance, occurred much less frequently than in the Phase II study."​ Defending the trial design, he continued: "This is a highly unfortunate chance observation that was impossible to address in the protocol."​ The company are also analysing the data to look for other variables that might have contributed to the failure. Currently, the only approved treatment for ischaemic strokes is Genentech's Activase. Another recombinant protein-based drug, the drug activates plasminogen, which in turn degrades blood clots. The market potential for drugs based on Factor VII is huge, especially in new indications such as ICH. Analysts estimate that world wide sales of all factor VII products could exceed $2bn (€1.5bn) by 2012, according to Maxygen. The US biotech develops Factor VII products in collaboration with Roche although the drugs are still in preclinical development. Marketed drugs that seek to enhance coagulation are Wyeth's ReFacto and BeneFix for the treatment of haemophilia A and haemophilia B respectively. ReFacto is based on Factor VIII and BeneFix on Factor IX. In a separate announcement, Novo recently said it will provide a "​significant unrestricted grant over the course of five years to help establish and grow"​ the non-profit American Thrombosis and Hemostasis Network (ATHN). The network was set up last year to advance and improve the care of individuals affected by bleeding and blood clotting disorders. It looks after a national database, which will be used to support clinical outcomes analysis, research, advocacy, and public health reporting.