Schering Plough e Pfizer presentano i dati delle fasi II degli anti-CCR5, una nuova classe di farmaci che speriamo tutti essere promettente. Ancora risicati, dal punto di vista numerologico e delle analisi immunologiche, le implicazioni a lungo termine.ANTI CCR5 SCH 417690, SVILUPPATO DALLA SCHERING-PLOUGH:

In this multi-center study, researchers evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of SCH 417690 monotherapy administered to HIV subjects. Forty eight HIV-infected individuals were enrolled into a sequential rising dose study to evaluate 10 mg, 25 mg and 50 mg BID of SCH 417690 versus placebo for 14 days. Within each of the three cohorts (N = 16), 12 subjects received SCH 417690 and 4 subjects received placebo in a randomized, blinded design.

Subjects were either treatment naïve or had had no antiretroviral treatment for a minimum of eight weeks prior to enrollment, had CCR5-tropic virus only, and had CD4+ counts > 200 cells/mm3. All subjects were followed for an additional 14 days after completion of dosing.


• SCH 417690 was safe and well tolerated.?Analysis of the pharmacokinetic profiles in the three dose levels showed dose proportionality with steady-state Cmin values above SCH 417690 IC90.

•There was a statistically significant dose-related suppression of HIV RNA across all three dose levels. Mean log10 reductions in HIV RNA were -0.93, -1.49, and -1.62 for the 10 mg BID, 25 mg BID, and 50 mg BID groups, respectively.

•The 25 and 50 mg BID doses showed a similar maximum antiviral effect that was superior to the 10 mg BID dose.

•HIV RNA slowly returned toward baseline after completion of dosing.

•CD4+ counts also improved during treatment.

Based on these findings, the authors conclude, “SCH 417690 demonstrated potent antiviral activity against CCR5-using HIV-1 strains at all doses studied. These findings, along with the marked post-antiviral effectthat lasted a number of days after completion of dosing, support further clinical development of SCH 417690.”


CCR5 antagonists, a type of entry inhibitor, have shown early promise in the treatment of HIV infection. In the current study, researchers at Pfizer summarize safety and efficacy data from selected multiple dose Phase 1/2a studies of the CCR5 antagonist maraviroc (UK-427,857), in healthy volunteers and HIV positive patients.

Six multiple dose studies where maraviroc was adminstered alone were reviewed. These studies included 7 days of dosing at the maximum dose studied of 1200mg QD and 28 days of dosing at the highest proposed clinical dose of 300mg BID.


• A total of 195 subjects (66 HIV+) were dosed with maraviroc, including 40 women.

• The most common treatment related adverse events were headache, dizziness, nausea, asthenia, flatulence and rhinitis. The majority of the adverse events were graded as mild or moderate.

•At doses up to and including 300mg BID the adverse event profile was similar to that of placebo.

•No serious adverse events were reported, with few (5) treatment-related discontinuation (3 with postural hypotension [2 on 600mg QD and 1 on placebo], 1 with elevated transaminases [3mg BID] and 1 with rash [placebo]).

•Clinically significant increases in liver function tests occurred in 7 subjects at varying doses of maraviroc with no clear frequency/dose relationship (4 subjects had >3xULN transaminases and 3 subjects had >1.25 to <2xULN bilirubin).

•Mild/moderate elevations in creatinine (<2xULN) were noted in one study at 1200mg QD and placebo.

•There was no dose related change in QTcF.

•Ten-day monotherapy with maraviroc at doses of 300mg QD and 300mg BID in HIV+ patients resulted in mean maximum HIV RNA reductions of 1.60 and 1.84 log10, respectively.

In conclusion, the authors note, “The development program to date has demonstrated that maraviroc is well tolerated at doses up to and including 300mg BID and that 10 day monotherapy resulted in significant reductions in viral load.”


D Schuermann and others. SCH 417690: Antiviral Activity of a Potent New CCR5 Receptor Antagonist. Abstract TuOa0205 (oral). 3rd IAS Conference on HIV Pathogenesis and Treatment. July 24-27, 2005. Rio de Janeiro, Brazil.

M McHale and others. Overview of phase 1 and 2a safety and efficacy data of maraviroc (UK-427,857). Abstract TuOa0204 (oral). 3rd IAS Conference on HIV Pathogenesis and Treatment. July 24-27, 2005. Rio de Janeiro, Brazil.