CMX001 shows strong in-vitro activity against HHV-6
Although studies have shown varying degrees of effectiveness for the current antiviral agents used to treat HHV-6 in the clinical setting (ganciclovir, foscarnet, and cidofovir), these molecules have inherent limitations including side effects and prospective antiviral resistance. In addition, there is currently no antiviral therapy approved for the specific treatment of HHV-6 infection, as the current options are all off-label usages of drugs approved for treatment of the closely related cytomegalovirus (HHV-5).
Pascale Bonnafous and Henri Agut from Paris have reported that a lipid-tagged version of cidofovir called HDP-CDV(licensed to Chimerix and in development for CMV as CMX001), displays enhanced antiviral efficacy against both HHV-6A and HHV-6B in vitro. HDP-CDV (CMX001) had a 700 to 1200X higher EC50 than cidofovir. Their report indicates increased efficacy against four separate strains of HHV-6B, three of which are known to have resistance to the antiviral known as cidofovir. Its enhanced antiviral activity is due to more efficient cellular uptake of drug due to the lipid conjugate, allowing cidofovir to enter the cell very efficiently. Due to this highly efficient process, a much smaller dosage can be utilized during clinical use, minimizing the risk of adverse side effects. Kidney toxicity has long been a limiting factor for the use of cidofovir in the clinical setting. The authors note that the HDP-CDV does not accumulate in kidney tubules, so nephotoxicity is expectedly lower than that of cidofovir. They also note that CMX001 was able to penetrate the liver and other tissues including the brain in large quantities, unlike cidofovir.
Taken together with previous reports of HDP-CDV’s favorable pharmacodynamic profile and limited risk of toxicity, along with encouraging results from drug trials conducted on CMX001 for the treatment of herpesviruses in several clinical settings, data from this report may increasingly argue in favor of using CMX001 for HHV-6 infection, particularly in cases of cidofovir resistance.
For more information, visit the HHV-6 Foundation webpages on current and future/alternative HHV-6 antiviral agents, and read the group’s full paper published in the Journal of Clinical Virology.