Sangamo BioSciences announces encouraging data from Phase II HIV trial
Sep 17, 2013 (MarketLine via COMTEX) --
Sangamo BioSciences, Inc., a clinical stage biopharmaceutical company, has announced new data from its ongoing Phase II clinical trial to evaluate a single infusion of the company's novel ZFP Therapeutic, SB-728-T, for the treatment of HIV/AIDS.
The data demonstrate functional control of the virus at or below the limit of detection in CCR5 delta-32 heterozygote HIV-infected subjects treated with SB-728-T.
Data from the late-breaking presentation demonstrate that viral load (VL) became undetectable during a treatment interruption (TI) from antiretroviral therapy (ART) in three of seven evaluable CCR5 delta-32 heterozygote HIV-infected subjects, including two of six subjects that had completed TI in the ongoing SB-728-902 Cohort 5 study and an additional subject from an earlier Phase I clinical trial of SB-728-T. In one SB-728-902 Cohort 5 subject, VL has remained undetectable (at or below the limits of quantification (LOQ) of the current ultra-sensitive assays for HIV) for seven weeks (to last measurement taken) and the TI is ongoing. Reduction in VL from peak during TI showed a statistically significant correlation (p=0.015) with estimated numbers of engrafted ZFN modified cells (SB-728-T) in which both copies of the CCR5 gene had been disrupted (biallelic modification), in line with previously presented data from this program.
"The data presented today demonstrate that a single infusion of SB-728-T can lead to profound suppression of viral load in the blood and sustained functional control of the virus," stated Dale Ando, M.D., Sangamo's vice president of therapeutic development and chief medical officer. "This is the first evidence that sustained functional control of HIV in the absence of ART is possible. The fact that three of the seven evaluable CCR5 delta-32 subjects achieved undetectable levels is a major step toward immunological functional control of HIV. We look forward to following these Cohort 5 subjects and presenting a complete data set from this study by the end of the year."
The effect on total CD4 counts in SB-728-T-treated subjects was significantly greater than those observed in previously published T-cell infusion studies without CCR5 modification and correlated with increased CD4 central memory and increased CCR5-disrupted central memory cells. In addition, a median 0.6 log reduction decrease in the size of the HIV reservoir at twelve months was observed, as demonstrated by measurement of HIV total DNA in peripheral blood mononuclear cells (PBMCs). The decrease in reservoir showed a statistically significant correlation with the improvement in CD4 count. Finally, data were presented describing possible predictors of robust CD4 T-cell reconstitution and immunological response post SB-728-T infusion.
"These data are extremely important and suggest that an immunological approach to control of HIV infection is obtainable," commented Rafick-Pierre Sekaly, Ph.D., Co-Director & Chief Scientific Officer of the Vaccine & Gene Therapy Institute of Florida (VGTI Florida), and a collaborator on the study. "SB-728-T treatment results in an unprecedented and durable increase in CD4+ cells primarily due to the expansion of central memory cells - CD4+ T-cell types that are vital for the successful reconstitution of the immune system in HIV-infected individuals. This enables functional control of virus and effects on the latent reservoir of HIV-infected cells that cannot be cleared by ART."
SB-728-T seems to both expand the total memory pool and, by CCR5 modification, protect a proportion of that pool from HIV entry, suggesting that SB-728-T treatment has the potential to durably reconstitute and protect an effective immune system in HIV-infected individuals.
"We are amassing a body of data suggesting that SB-728-T treatment can potentially enable attacks on HIV infection from several angles," said Geoff Nichol, M.B., Ch.B., Sangamo's executive vice president of R&D. "Our aim is to provide a protected reservoir of immune memory cells to replenish the cells killed by HIV and to generate an effective immune response against the virus and opportunistic infections. Some HIV-infected individuals, so-called 'elite controllers,' can accomplish this without drug intervention. These individuals typically have low CCR5 expression and good anti-viral CD8 responses, a characteristic shared by those SB-728-T treated subjects in which we have to date seen the greatest effects on the virus. We have demonstrated that SB-728-T treatment results in a durable increase in total CD4 T-cells and, in these presentations, an effect on controlling the acute rebound in viral load off ART, and a longer term effect on the viral reservoir, a source of HIV which is not addressed by current anti-retroviral therapies. The data will be used to optimize the development of this therapy as a functional cure for HIV."
Dr Nichol added, "In addition to our SB-728-902 Cohort 5 study, we have a second ongoing trial (SB-1101) designed to maximize the engraftment of SB-728-T in subjects who are not CCR5 delta-32 heterozygotes and who represent the vast majority of HIV-infected individuals. Maximizing circulating SB-728-T is important, as viral control appears related to the extent of engraftment. This trial is evaluating escalating doses of a preconditioning drug, cyclophosphamide (Cytoxan), which is used to transiently reduce the numbers of T-cells in the body. The cells rapidly repopulate once the drug is discontinued, an effect that can enhance engraftment of concurrently administered exogenous T-cells such as SB-728-T. We intend to present data from all dose-escalation cohorts in these studies before the end of 2013."
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