AiCuris Promising Drugs Against Herpes Simplex (AIC316) and Human Cytomegalovirus (Letermovir, AIC246) in Preparation for Phase III
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|Tuesday, 07 August 2012 14:30 (UTC + 2)|
Key note at International Herpesvirus Workshop Calgary, Canada
Wuppertal, Germany, August 7, 2012 / B3C newswire / – AiCuris will present at the International Herpesvirus Workshop in Calgary, Canada, on its two front-running compounds targeting herpes viruses, on August 8th 2012 at 2 pm, in the plenary session on interventions.
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 II 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 III 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.”
About Human Cytomegalo Virus (HCMV)
HCMV disease is characterised by fever, leucopenia (very low white blood cells) and thrombocytopenia (very low platelet numbers) with or without specific organ dysfunction. Two main strategies to prevent HCMV disease have been adopted: anti-HCMV drug prophylaxis or pre-emptive treatment of transplant recipients who are at risk or have evidence of HCMV infection upon screening.
Besides transplant recipients, newborn children are highly threatened by HCMV infections. The infection can be acquired before, during or after birth and can lead to severe neurological damage or death. Because of the side effects of presently available drugs against HCMV, it is nearly impossible to treat these children. Neither can pregnant women with an active HCMV infection be treated.
Patients with AIDS might suffer from HCMV infection or disease, once HIV has caused severe immune deficiency. In these patients, the virus might affect various organs and may e.g. lead to blindness or life threatening pneumonia. Thanks to HAART, AIDS cases with HCMV disease have become rare in the Western world. But in countries where access to anti-HIV therapy is not freely available such HCMV infections are more common.
Increasing evidence is accumulating that even subclinical HCMV replication may be harmful, as HCMV is a virus, which is immune-suppressive on its own. For HIV-infected individuals several recent investigations showed that even when HIV is well-suppressed by HAART, the patients may not be able to control HCMV very well and may, as a consequence, suffer from a chronic and deleterious inflammation.
Similarly, HCMV also appears to pose a risk to patients under intensive care (e.g. after heart attack, suspected sepsis or burn). In this patient group, an active HCMV infection was found to be associated with increased time of hospitalisation and increased risk of death. Furthermore, in patients being treated for an auto-immune disease by the administration of immuno-suppressive agents, it has been observed that an opportunistic HCMV infection may occur.