January 12, 2012
President, Chief Executive Officer
Geoffrey Nichol M.B., Ch.B.
Executive Vice President, Research and Development
H. Ward Wolff
Executive Vice President and Chief Financial Officer
David G. Ichikawa
Senior Vice President, Business Development
Dale Ando, M.D.
Chief Medical Officer and Vice President, Therapeutic Development
Philip D. Gregory, D. Phil.
Chief Scientific Officer and Vice President, Research
Point Richmond Tech Center II
501 Canal Blvd,
Richmond, CA 94804
In response to the press release issued by Sangamo BioSciences on January 9th 2012, the undersigned individuals and organizations are writing to express concern about the status of the SB-728-T development program. Firstly, we wish to emphasize that we salute and support your company’s work in developing SB-728-T and conducting the clinical trials that have highlighted its promise as a therapy for HIV infection. We recognize that the challenges involved in developing gene- and immune-based therapies for HIV infection are significant and that Sangamo BioSciences has shown impressive commitment to surmounting them, and we vigorously support your effort to achieve a “functional cure” for HIV.
Our concern is that while your press release highlights Sangamo BioSciences commitment to using zinc finger nuclease technology to address “unmet medical needs,” it is silent on the status of further research for SB-728-T in the HIV-positive population with arguably the greatest unmet medical need: those who experience poor immune reconstitution despite suppression of HIV replication by antiretroviral therapy (ART). Although the exact definitions of such “discordant” responses to ART can vary, the literature consistently reports that a substantial proportion (~5-20%) of individuals initiating ART will experience a suboptimal immunological response, with older age and lower CD4 at initiation being the major risk factors, and many studies have now reported that people experiencing poor immune reconstitution on ART face a significantly higher risk of illness and mortality (e.g. Gilson 2009; Tan 2008; Van Lelyveld 2011; Zoufaly 2011).
For this reason we are writing to encourage Sangamo BioSciences—in the strongest possible terms—to continue to pursue the development of SB-728-T for this population by instituting additional clinical trials for people with poor immune reconstitution on ART. Additional support for this research might be obtainable by collaboration with government-sponsored networks such as the AIDS Clinical Trials Group (ACTG) or INSIGHT, and we would be extremely willing to assist in exploring this possibility. The immunological responses documented in your trials to date have been impressive, and in particular the magnitude of the improvement in CD4:CD8 ratios is unprecedented. Because inverted CD4:CD8 ratios are a poor prognostic indicator in elderly individuals without HIV infection, this latter finding suggests that SB-728-T may have unique potential to provide long-term clinical benefits by ameliorating the additional impact of the immune dysregulation caused by HIV infection on the immune alterations that accompany natural aging. The preliminary CD4:CD8 ratio data also underscore the potential of SB-728-T to benefit the population of people with HIV who are at risk for poor immune reconstitution on ART due to older age.
We also believe that these promising results place an ethical obligation upon Sangamo BioSciences to continue to provide treatment to the participants in these trials.
As community advocates with a long history of productive dialogues with industry regarding the development of therapeutic candidates, we are eager to meet with representatives from Sangamo BioSciences to discuss this issue and would be grateful if a meeting could be scheduled at your earliest possible convenience.
AIDS Action Baltimore
AIDS Policy Project
AIDS Treatment Activists Coalition
Program for Wellness Restoration
National AIDS Treatment Advocacy Project
Test Positive Aware Network
The Zephyr LTNP Foundation
Treatment Action Group
Matt Chappell LCSW
David Evans, Project Inform
Email: DEvans@projectinform.org, Tel: (626) 241-8267
Richard Jefferys, Treatment Action Group
Email: email@example.com, Tel: (212) 253-7922
Gilson RJ, Man SL, Copas A, et al. Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study. HIV Med. 2010 Feb;11(2):152-60.
Tan R, Westfall AO, Willig JH, et al. Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2008;47(5):553–8.
Van Lelyveld SF, Gras L, Kesselring A, et al. Long term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort. AIDS. 2011 Nov 22. [Epub ahead of print]
Zoufaly A, an der Heiden M, Kollan C, et al. Clinical outcome of HIV-infected patients with discordant virological and immunological response to antiretroviral therapy. J Infect Dis. 2011 Feb 1;203(3):364-71. Epub 2010 Dec 8