FP-21399 (Lexigen Pharmaceuticals).
Lexigen (formerly Fuji ImmunoPharmaceuticals) is developing FP-21399, a bis-azo compound, for the potential treatment of HIV infections. By March 1998, a phase II clinical study had been initiated to explore the immunologic and virologic activity of the compound. In the phase II study, the compound was being administered once a month for 48 weeks to 40 patients who are failing on protease inhibitor regimens either alone or with the antiretrovirals currently being taken by the patients. In a previous phase II study conducted by the company, researchers observed hints of a cellular immune response in a small subset of subjects at risk for disease progression or development of opportunistic infections [310177]. Phase I clinical trials commenced in the US in 1995 [178794]. In a small 21-patient phase I dose escalation trial of intravenous FP-21399, 13 patients with baseline CD4 cell counts between 50 and 400 received infusions of various doses (1,2 or 3 mg/kg) of the compound once a week for four weeks. The compound was well-tolerated and 9 patients showed an increase in CD4 count of at least 15% over their baseline values, 2 showed a decrease in viral load of 1 log (90%), and 2 went from low viral loads to below the limit of quantification [310771,310177]. FP-21399 has been reported to interfere with the ability of the HIV envelope glycoproteins to use CXCR4 and CCR5 as co-receptors when entering CD4 cells. It concentrates in the lymph nodes, which are important viral reservoirs. In addition, the drug has demonstrated antiviral activity against many clinical and laboratory strains of HIV, including those that are AZT-resistant [310177]. FP-21399 was selected via a screening program of Fuji's compounds developed originally for photographic use. It has been demonstrated, in preclinical studies, that FP-21399 inhibits HIV entry to the target cell by interfering with the V3 loop of the viral envelope. The compound has the advantage that it has lower toxicity than reverse transcriptase inhibitors because it does not enter the cells [178794].
Poli
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Istituto Scientifico H San Raffaele, DiBit, via Olgettina 58, Milano 20132, Italy. polig@dibit.hsr.it
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