The molecule is an azo derivative of an active molecule (UR-12715, anti-TNFalpha and PAF antagonist ) and 5-aminosalicylic acid (5-ASA), the gold standard treatment for mild to moderate ulcerative colitis.

5-ASA derivatives exhibit anti-inflammatory activity and are widely used in the treatment of mild to moderate UC. Additionally, UR-12715 has been shown to inhibit TNFalpha and other important cytokines, which play key roles in the pathogenesis of UC.

The addition of UR-12715 has shown some synergistic activities to 5-ASA and a higher activity profile in animal models. Thus, the inhibition of TNF-alpha and the addition of PAF antagonism to 5-ASA in dersalazine sodium may provide a new therapeutic alternative with a higher efficacy than simple aminosalicylate treatments that may help patients to avoid the adverse effects commonly associated with the use of up-escalating therapies like corticosteroids and immunosuppressants.

Development

Dersalazine sodium has demonstrated its safety in a thorough program of toxicology and safety pre-clinical studies. The intrinsic activity of dersalazine sodium, of the active metabolite UR-12715, and its synergy with 5-ASA have all been shown in several animal models of acute and chronic relapsing colitis. In addition, the occurrence of colonic azo-reduction and the minimal systemic availability of dersalazine sodium has been demonstrated in several animal species in pre-clinical studies and in clinical studies.

Dersalazine sodium has been tested for safety and pharmacokinetics in single and multiple escalating dose placebo controlled studies in healthy volunteers, and has shown to be safe and well tolerated. The product pharmacokinetics in humans has been assessed in these studies and also using radiolabelled compound, confirming minimal dersalazine sodium disposition and an extensive azo-reduction by colon bacteria.

An ongoing new Phase II double-blind randomized active and placebo controlled
multicenter trial includes patients with mild to moderate UC. Results are due at the end
of 2009.

 

Phase II

EP 01940316.1    Granted
US 10/257262     Granted
JP 2001-575582   Pending

Palau Pharma is currently seeking a licensing partner for the worldwide development and commercialisation of dersalazine sodium.