B3C newswire / - AiCuris announces today that it will present the results of the resistance analysis from the recently completed phase II clinical trial with AIC316 at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in USA, Chicago, 17 - 20 September, 2011 (Session 112, 18th September 2011 at 11:15 am, Presentation V-941b). AIC316 is one of AiCuris lead compounds and was tested in patients with genital herpes (herpes simplex virus type 2, HSV-2). AiCuris' project leader and senior scientist Dr. Alexander Birkmann will present the work, which was conducted in collaboration with the University of Washington, Seattle.
In the trial 156 HSV-2 positive subjects were randomized to either one of four AIC316 treatment groups or to placebo. Objective of the trial was to compare the efficacy of different doses of AIC316 (5, 25, and 75 mg once daily and 400 mg once weekly) and placebo with respect to the suppression of HSV mucocutaneous shedding under treatment. Trial participants provided daily swabs of their genital area that were analyzed for HSV DNA. Treatment with AIC316 was safe and well tolerated. A significant and dose dependent reduction of both viral DNA and days with HSV lesions could be demonstrated.
Positive swabs were subjected to DNA sequence analysis and sequence data of relevant regions in the viral UL5 helicase and UL52 primase genes (the molecular targets of AIC316) were compared with the HSV-2 reference sequence. It could be shown that under treatment with AIC316 in this phase II trial there was no emergence of viruses with any of the recognized resistance mutations.
"The fact that no potentially resistance mediating mutations were detected under AIC316 treatment is very encouraging" says Professor Helga Ruebsamen-Schaeff, CEO of AiCuris, "As we saw a clear dose-response within our trial, this result also means that even under a suboptimal therapy at the lower dose, which allowed some viral growth, no resistant mutants escaped."
About HSV
Herpes simplex viruses (HSV) are widespread in the human population (seroprevalence up to 100%, depending on geographic area and subpopulation), and are divided into herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). While HSV-1 predominantly causes oral lesions (cold sores), HSV-2 manifests in the genital region and is mainly transmitted sexually. However, the past decade has seen an increase in HSV-1 genital infections, which now account for at least half of first episodes of genital herpes in some countries. Both labial and genital herpes are generally self-limiting but can recur frequently. HSV infections have also been associated with a three-fold increase in the risk of sexually acquired HIV. In immune compromised individuals large and painful ulcerations may result, and newborns infected with HSV are at risk of developing a very dangerous herpes encephalitis. Unlike most of the current herpes drugs, which inhibit a specific viral enzyme, the DNA polymerase, AIC316 acts by a unique mechanism of viral inhibition. Currently available therapies share the same mode of action and are therefore similar in their efficacy, whilst in addition exhibiting possible cross-resistance. Based on its unique mode of action AIC316 not only is highly potent but it also is active against viruses, which have become resistant to existing drugs.
In the trial 156 HSV-2 positive subjects were randomized to either one of four AIC316 treatment groups or to placebo. Objective of the trial was to compare the efficacy of different doses of AIC316 (5, 25, and 75 mg once daily and 400 mg once weekly) and placebo with respect to the suppression of HSV mucocutaneous shedding under treatment. Trial participants provided daily swabs of their genital area that were analyzed for HSV DNA. Treatment with AIC316 was safe and well tolerated. A significant and dose dependent reduction of both viral DNA and days with HSV lesions could be demonstrated.
Positive swabs were subjected to DNA sequence analysis and sequence data of relevant regions in the viral UL5 helicase and UL52 primase genes (the molecular targets of AIC316) were compared with the HSV-2 reference sequence. It could be shown that under treatment with AIC316 in this phase II trial there was no emergence of viruses with any of the recognized resistance mutations.
"The fact that no potentially resistance mediating mutations were detected under AIC316 treatment is very encouraging" says Professor Helga Ruebsamen-Schaeff, CEO of AiCuris, "As we saw a clear dose-response within our trial, this result also means that even under a suboptimal therapy at the lower dose, which allowed some viral growth, no resistant mutants escaped."
About HSV
Herpes simplex viruses (HSV) are widespread in the human population (seroprevalence up to 100%, depending on geographic area and subpopulation), and are divided into herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). While HSV-1 predominantly causes oral lesions (cold sores), HSV-2 manifests in the genital region and is mainly transmitted sexually. However, the past decade has seen an increase in HSV-1 genital infections, which now account for at least half of first episodes of genital herpes in some countries. Both labial and genital herpes are generally self-limiting but can recur frequently. HSV infections have also been associated with a three-fold increase in the risk of sexually acquired HIV. In immune compromised individuals large and painful ulcerations may result, and newborns infected with HSV are at risk of developing a very dangerous herpes encephalitis. Unlike most of the current herpes drugs, which inhibit a specific viral enzyme, the DNA polymerase, AIC316 acts by a unique mechanism of viral inhibition. Currently available therapies share the same mode of action and are therefore similar in their efficacy, whilst in addition exhibiting possible cross-resistance. Based on its unique mode of action AIC316 not only is highly potent but it also is active against viruses, which have become resistant to existing drugs.
