Kappaproct was developed by InDex Pharmaceuticals of Sweden, a country where the incidence of ulcerative colitis and other forms of inflammatory bowel disease is among the highest in Europe.
The agreement gives Serono exclusive worldwide rights to develop and commercialise the antisense drug for the treatment of ulcerative colitis and potentially other inflammatory diseases, and it will pay InDex up to $35 million (EUR 28m) if the drug is commercialised in at least one indication.
Ulcerative colitis affects up to 13 per cent of people in Sweden, and occurs mainly in young people, with disease onset typically between the ages of 20 and 30 years. There is no cure, and treatment is targeted at managing symptoms using steroids and 5-aminosalicylic acid.
The most common symptoms of ulcerative colitis are abdominal discomfort and frequent loose stools. However, patients may also experience fatigue, weight loss, loss of appetite, rectal bleeding, loss of body fluids and nutrients, and severely affected patients can develop fever, bloody diarrhoea, nausea, and abdominal cramps.
And if the high incidence of the disease and the debilitating symptoms associated with it were not enough, ulcerative colitis may also cause non- intestinal problems such as arthritis, inflammation of the eye, liver disease and anaemia. Between 25 and 40 percent of ulcerative colitis patients are unresponsive to current treatment, and ultimately require surgery to remove the colon. Moreover, patients with long-standing ulcerative colitis disease are at considerable risk of developing colorectal cancer.
Kappaproct is an antisense inhibitor of the p65 protein, a key activator of a pro-inflammatory pathway hinging on a protein called NF-kappa B. This pathway is also being targeted in the development of new drugs to treat arthritis.
Prior research has shown that 5-ASA, which has long been used to treat ulcerative colitis and the related Crohn's disease, prevents the activation of NF-kappa B. The latter is a transcription factor that, when activated, moves from the cytoplasm of the cell into the nucleus to stimulate the production of pro-inflammatory cytokines. The hope is that an antisense approach will overcome the major problems with 5-ASA, namely that it has significant side effects making it unusable in 15 per cent of patients.
Kappaproct is currently being tested in a Phase II clinical trial for active ulcerative colitis which will involve 150 patients. In a completed proof-of-concept, double-blind placebo-controlled clinical trial in patients with therapy-resistant inflammatory bowel disease, it was shown that the majority of these patients responded positively to a single dose of the antisense drug, with only mild adverse effects.