Dextrin-2-Sulfate

Dextrin-2-sulfate (D2S, Viraldon®) is a synthetic derivative of dextrin with potent activity against HIV-1. Developed by ML Laboratories, dextrin-2-sulfate is administered via the IP route and is therefore reserved for late stage therapy of HIV-infected patients who have not responded to, or cannot tolerate, other treatments. Aphase III study (TITAN) in the UK is being carried out in which participants are required to be on stable antiretroviral therapy for 3 months before entering the trial and agree to keep up stable treatment for a further 6 months. Centres in South Africa were approached to participate in the study after an initial shortage of eligible patients in the UK, related to the introduction of protease inhibitor tablet treatments. MLLaboratories believed this situation would decline because of a lack of continued efficacy of protease inhibitor treatments combined with unacceptable adverse effects. However, this has not occurred as quickly as the company had expected.

ML Laboratories has licensed North American rights to dextrin sulfate to General Medical Industries (GMI) of Virginia, USA. GMI will fund an 80-patient study (ATLAS) in the US as well as other trials necessary for regulatory approval in that country.Dextrin-2-sulfate is available on a compassionate use basis, which will provide additional data for a product licence application scheduled for the last quarter of 2000.

An intravaginal gel formulation of dextrin-2-sulfate, Emmelle®, is being developed for the prevention of HIV transmission between heterosexuals. The UK Medical Research Council has adopted Emmelle® as a lead product for this indication. Two phase I evaluations in female volunteers have been completed and recruitment is underway in the UK for a phase II trial in which 200 healthy sexually active female volunteers will be randomised to receive Emmelle® or placebo over 28 days. It is hoped that 50male sexual partnerswill also be recruited to investigate the effect of the product onmen. Further clinical studies are planned in Europe and Africa.

Dextrin-2-sulfate exhibited the most favourable combination of high anti-HIV-1 activity and low anticoagulant activity compared with other structural analogues of sulfated polysaccharides. Clinically, however, the need for IP administration limits its usefulness to late-stage HIV-infected patients who have not responded to, or cannot tolerate, other treatments. Once clinical data are available for the intravaginal gel formulation the potential of this product can be more fully evaluated.