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IDX899 Demonstrates Rapid and Profound Inhibition of HIV Replication in a Phase I/II Clinical Trial in Treatment-Naive HIV-Infected Patients

Thursday, February 7, 2008 General News J E 4
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CAMBRIDGE, Mass., Feb. 6 Idenix Pharmaceuticals,Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery anddevelopment of drugs for the treatment of human viral and other infectiousdiseases, today reported data for IDX899, a non-nucleoside reversetranscriptase inhibitor (NNRTI) being developed for the treatment of HIV. Inthe first dosing cohort of an ongoing phase I/II study, eight HIV-1 infectedtreatment-naive patients receiving 800 mg of IDX899 once-daily achieved a meanreduction in virus level of 2.01 log(10), or 99 percent, after seven days oftreatment. Additionally, two posters detailing the in-vitro resistance andpharmacokinetic profile in man of IDX899 were presented at the 2008 Conferenceon Retroviruses and Opportunistic Infections (CROI) this week in Boston, MA.

"New once-a-day NNRTIs that offer improved resistance and safety profilesover what is currently available would be a valuable asset to HIV-treatingphysicians," said Dr. Douglas Richman, Professor of Pathology and Medicine,University of California San Diego, and Director of the UCSD Center for AIDSResearch. "The early profile of IDX899 shows promise and warrants continuedclinical evaluation as a potential HIV therapy."

Interim Proof of Concept Data in HIV-infected Patients

An ongoing phase I/II clinical trial is evaluating the safety,tolerability and antiviral activity of IDX899. In the first cohort of thestudy, ten HIV-1-infected treatment-naive patients were randomized 8:2 toreceive once-daily 800 mg IDX899 or matching placebo, respectively, for sevendays.

Patients receiving once-daily 800 mg of IDX899 achieved a mean and medianplasma viral load reduction of 2.01 and 2.11 log(10), respectively, afterseven days of treatment. Six out of eight patients achieved a 2 log(10) orgreater reduction in viral load with one patient achieving undetectable viruslevels (< 50 copies/mL). No serious adverse events were reported in thiscohort and no patients discontinued the study. Given the potent antiviralactivity and favorable preliminary safety demonstrated at 800 mg once-daily,we will explore sequential cohorts of 400 mg once-daily followed by 200 mgonce-daily.

"We are pleased with the safety profile and potency observed with the 800mg dose of IDX899 in HIV-infected patients and based on these data we willcontinue to evaluate lower dosing regimens in order to optimize the role ofIDX899 in HIV combination therapy," said Douglas Mayers, M.D., Idenix's chiefmedical officer.

In-vitro Resistance Data

In a preclinical resistance study, IDX899 and other marketed andinvestigational NNRTIs were compared to evaluate in-vitro genotypic resistanceand phenotypic cross-resistance profiles. IDX899 demonstrated potent antiviralactivity against established NNRTI-resistant clinical isolates. Compared toefavirenz (Sustiva(R)), the emergence of IDX899-resistant HIV-1 isolates wasslower and required several mutations suggesting a higher barrier toresistance for IDX899. The resistance mutations selected in-vitro with IDX899were different from those selected with efavirenz. Efavirenz appeared to beactive against IDX899 resistant viruses and IDX899 remained active againstefavirenz-resistant virus containing as many as four NNRTI-resistancemutations.

Safety, Pharmacokinetics and Drug-Drug Interaction Data in HealthyVolunteers

A phase I study was conducted to evaluate the safety and pharmacokineticsof IDX899 following single escalating (n=65) and multiple (n=20) doses inhealthy volunteers. In this study, following once-daily oral administration,IDX899 appeared to be well tolerated at single doses up to 1200 mg andmultiple doses up to 800 mg over a seven-day period. No serious adverseevents or pattern of laboratory abnormalities were observed. Food enhancedthe absorption of IDX899. Additionally, in a single-dose drug-druginteraction stu
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