Here’s the IDX899 PR from CROI that we’ve been waiting for; it contains a lot of information because it reports the results from three studies: a phase-1/2 trial in HIV patients, an in vitro resistance study, and a PK study in healthy volunteers. The highlights: i) IDX899 monotherapy produced slightly more than 2 logs of viral-load reduction after seven days of treatment; ii) there were no troubling side effects; iii) the resistance profile of IDX899 was superior to Sustiva’s in the in vitro analysis; iv) there was no cross-resistance to or from Sustiva; and v) there was no drug interaction with Reyataz (the most widely used PI in treatment-naïve HIV). Additional cohorts in the phase-1/2 study will evaluate lower doses.
>> IDX899 Demonstrates Rapid and Profound Inhibition of HIV Replication in a Phase I/II Clinical Trial in Treatment-Naive HIV
Wednesday February 6, 5:30 pm ET
CAMBRIDGE, Mass., Feb. 6 /PRNewswire-FirstCall/ -- Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX ), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases, today reported data for IDX899, a non-nucleoside reverse transcriptase inhibitor (NNRTI) being developed for the treatment of HIV. In the first dosing cohort of an ongoing phase I/II study, eight HIV-1 infected treatment-naive patients receiving 800 mg of IDX899 once-daily achieved a mean reduction in virus level of 2.01 log(10), or 99 percent, after seven days of treatment. Additionally, two posters detailing the in-vitro resistance and pharmacokinetic profile in man of IDX899 were presented at the 2008 Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston, MA.
"New once-a-day NNRTIs that offer improved resistance and safety profiles over what is currently available[i.e. Sustiva]would be a valuable asset to HIV-treating physicians," said Dr. Douglas Richman, Professor of Pathology and Medicine, University of California San Diego, and Director of the UCSD Center for AIDS Research. "The early profile of IDX899 shows promise and warrants continued clinical 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 the study, ten HIV-1-infected treatment-naive patients were randomized 8:2 to receive once-daily 800 mg IDX899 or matching placebo, respectively, for seven days.
Patients receiving once-daily 800 mg of IDX899 achieved a mean and median plasma viral load reduction of 2.01 and 2.11 log(10), respectively, after seven days of treatment. [It’s unusual for the mean to be less than the median for this metric because is typically an outlier or two at the high end.] Six out of eight patients achieved a 2 log(10) or greater reduction in viral load with one patient achieving undetectable virus levels (< 50 copies/mL)[it would be helpful to know the viral load of this patient at baseline]. No serious adverse events were reported in this cohort and no patients discontinued the study. Given the potent antiviral activity and favorable preliminary safety demonstrated at 800 mg once-daily, we will explore sequential cohorts of 400 mg once-daily followed by 200 mg once-daily.
"We are pleased with the safety profile and potency observed with the 800 mg dose of IDX899 in HIV-infected patients and based on these data we will continue to evaluate lower dosing regimens in order to optimize the role of IDX899 in HIV combination therapy," said Douglas Mayers, M.D., Idenix's chief medical officer.
In-vitro Resistance Data
In a preclinical resistance study, IDX899 and other marketed and investigational NNRTIs were compared to evaluate in-vitro genotypic resistance and phenotypic cross-resistance profiles. IDX899 demonstrated potent antiviral activity against established NNRTI-resistant clinical isolates. Compared to efavirenz (Sustiva®), the emergence of IDX899-resistant HIV-1 isolates was slower and required several mutations suggesting a higher barrier to resistance for IDX899. The resistance mutations selected in-vitro with IDX899 were different from those selected with efavirenz. Efavirenz appeared to be active against IDX899 resistant viruses and IDX899 remained active against efavirenz-resistant virus containing as many as four NNRTI-resistance mutations.
Safety, Pharmacokinetics and Drug-Drug Interaction Data in Healthy Volunteers
A phase I study was conducted to evaluate the safety and pharmacokinetics of IDX899 following single escalating (n=65) and multiple (n=20) doses in healthy volunteers. In this study, following once-daily oral administration, IDX899 appeared to be well tolerated at single doses up to 1200 mg and multiple doses up to 800 mg over a seven-day period. No serious adverse events or pattern of laboratory abnormalities were observed. Food enhanced the absorption of IDX899. Additionally, in a single-dose drug-drug interaction study assessing the combination of either 100 or 800 mg IDX899 and 100 mg atazanavir (Reyataz®), atazanavir plasma levels were not markedly altered by IDX899. [This is important because Reyataz is the most widely used PI and the second-most-widely used drug of any class to be added to Truvada in treatment-naive HIV.]
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus and HIV. For further information about Idenix, please refer to www.idenix.com. <<
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