AiCuris’ two lead herpes-targeting compounds, AIC316 and letermovir (AIC246) have successfully completed double-blinded, placebo-controlled Phase 2 dose-ranging trials, meeting the primary and secondary study endpoints with excellent and dose-proportional efficacy and a good safety profile. Both compounds can be administered orally once daily for prophylaxis and suppression of the virus. The long halflife of AIC316, in addition, likely allows dosing only one pill per herpes episode.
AIC316 and letermovir are non-nucleosidic drugs and act via a novel mode of action targeting viral enzymes different from polymerases: AIC316 is an inhibitor of the viral helicase-primase of herpes simplex 1 and -2 virus, while letermovir inhibits the viral terminase of HCMV. Based on these novel modes of action the compounds offer significant benefits over existing polymerase-inhibitors:
• AIC316 does not need to be activated inside the cell by a viral enzyme and thus protects uninfected cells from infection. In addition, the very long halflife of the compound allows to protect uninfected cells over extended periods of time, in contrast to the nucleoside analogues in the market. These features result in fast onset of action and powerful suppression of viral shedding.
• Letermovir, by addressing a target at a critical step of the virus life cycle, exhibits a very steep dose-response curve and is able to suppress high viral loads. This has led to highly significant suppression of HCMV in the Phase 2 trial, when the drug was given prophylactically. In addition, as the target of letermovir does not exist in the human body there is no target-related toxicity as is seen with the marketed nucleoside analogues and the drug has a very good safety profile.
“Given the fact that there has been no innovation in the treatment of Herpes or Human Cytomegalovirus for years, we are extremely proud of having created two very innovative drugs, which are in preparation for Phase 3 and which hopefully will make a major difference for patients suffering from these viral infections and disease conditions. Based on their novel modes of action they will also be active against viruses which have acquired resistance against the marketed drugs”, says Prof. Helga Rübsamen-Schaeff, CEO at AiCuris.
Regarding AIC316 AiCuris’ project leader Dr. Alexander Birkmann adds: “The benefit of strongly suppressed viral shedding combined with protection of uninfected cells, may even reduce the viral burden in herpes patients treated long term or repeatedly over time and may reduce the frequency and severity of outbreaks, which is not achievable by present drugs.”
Date: August 7, 2012
Source: AiCuris
Filed Under: Drug Discovery
