Theraclone Sciences, Inc., a therapeutic antibody discovery and development company based in Seattle, Wa., recently announced results from a Phase 2a viral challenge study of TCN-032 for the universal treatment of influenza A.
The results represent the first demonstration that a non-neutralizing antibody can provide immediate immunity and potential therapeutic benefit in influenza. TCN-032 is a recombinant fully human monoclonal antibody being developed for the treatment of patients hospitalized with severe influenza A infection and as a stockpiled product for preventative and therapeutic treatment options in the event of pandemic flu outbreaks.
In the study, TCN-032 treatment resulted in significant reductions in clinical symptoms score as well as viral load as compared to placebo-treated subjects. While the Phase 2a study did not meet its pre-specified primary endpoint, the overall data support an anti-influenza effect, providing the impetus to proceed to clinical studies in patients with natural infection. TCN-032 was well-tolerated with no serious adverse events or immunogenicity observed.
“TCN-032’s mechanism of action holds promise as an alternative or additional therapy to current treatments, particularly in cases of anti-viral resistance potentially providing an important new treatment option for patients with influenza, including those who are hospitalized with serious disease,” said Michael G. Ison, MD, MS, FIDSA, an Associate Professor at Northwestern University Feinberg School of Medicine and Medical Director, Transplant & Immunocompromised Host Infectious Diseases Service. “These data suggest that TCN-032 likely has antiviral activity and should be further evaluated in clinical studies.”
Theraclone leverages its proprietary antibody discovery technology, I-STAR (In-Situ Therapeutic Antibody Rescue), to identify rare human antibodies that may be developed into antibody product candidates that are potentially safer and more effective than current therapies.
“We are highly encouraged by the biological efficacy demonstrated in this Phase 2a study,” added Eleanor Ramos, M.D., Chief Medical Officer, Theraclone. “TCN-032 was developed using our I-STAR technology for its ability to target a highly conserved portion of the influenza virus, including highly pathogenic or pandemic strains such as H5N1 and H1N1, and the emerging H7N9, greatly reducing the likelihood of the virus developing resistance to this antibody.”
The randomized, placebo-controlled, double-blind Phase 2a study was designed to assess the safety and efficacy of TCN-032 in normal human volunteers challenged with influenza A infection. Twenty-four hours after viral inoculation, subjects were randomized 1:1 to TCN-032 or placebo and monitored for development of clinical symptom scores and viral load.
A total of 61 subjects were randomized, of whom 60 received intravenously administered study drug, TCN-032, at a dose of 40 mg/kg, or placebo. A total of 48 subjects met the definition of laboratory-confirmed infection (TCN-032, n=24 and placebo n=24). A numerical reduction in the primary efficacy parameter of the proportion of subjects who developed any grade 2 or greater influenza symptom or pyrexia was observed, but not statistically significant (p>0.10). TCN-032 treated subjects showed significant reductions in both clinical symptom scores and viral load via qPCR. Median clinical symptom AUC (Day 1-7) was reduced by 35% (p=0.047, Wilcoxon rank-sum test) in TCN-032 subjects compared to placebo. Time to resolution and duration of symptoms, and nasal mucus weights were reduced in TCN-032 subjects compared to placebo. Median viral AUC (by qPCR, Day 2-7) was reduced by 2.2 log10 TCID50/mL*Day (p=0.095, Wilcoxon rank-sum test) in TCN-032 subjects compared to placebo. Viral resistance analysis showed no change in the epitope recognized by TCN-032.
The trial was supported in part by Zenyaku Kogyo Co., Ltd. through its multi-year research and development agreement with Theraclone to identify and develop candidates for the treatment of pandemic and serious seasonal influenza. Zenyaku Kogyo has an exclusive license in the territory of Japan to Theraclone’s influenza monoclonal antibody program. Theraclone retains worldwide development and commercialization rights outside of Japan and is currently seeking additional commercial partners in other territories of the world.
Theraclone Sciences and PharmAthene announced a definitive merger agreement in August 2013.
Source: Theraclone Sciences