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Sangamo HIV Gene Therapy Trials: Until There's A Functional Cure, Treatment!

Signaling significant progress for research into a functional cure for HIV, Sangamo BioSciences in Richmond, Calif., has announced the start of 2 new clinical trials using SB-728-T, its HIV zinc finger gene therapy technology. Sangamo is the company furthest along in gene therapy for HIV disease.

The zinc finger technology is a method that collects a person's own CD4 T-cells, expands them in the laboratory, and uses a zinc finger nuclease to disrupts the gene for the CCR5 co-receptor. CCR5 is one of the co-receptors HIV uses to attach to CD4 cells, and the process essentially makes the cells resistant to infection. This could potentially lead to a functional cure, defined as complete suppression of HIV without using antiretroviral drugs.

Data from 2 earlier trials were presented in 2011, showing remarkable results thus far in immunological non-responders, or people who have not achieved adequate CD4 cell gains despite viral suppression on antiretroviral therapy.

According to a recent Sangamo press release, the new trials are opening ahead of schedule. "Data from earlier Phase 1 trials demonstrated a statistically significant relationship between the number of circulating T-cells in which both CCR5 genes are modified and the reduction in HIV viral load in infected subjects during an interruption of antiretroviral therapy," said Geoff Nichol, MB, ChB, Sangamo’s Executive Vice President. "Both of these new Phase 2 clinical trials are specifically designed to confirm and further investigate these findings."

The company is clearly on a roll, according to Edward Lanphier, Sangamo's President and CEO, who reports that the company is in the black with $85 million in cash as of December 2011. For a small biotech, they appear to have plenty of resources to move ahead with this exciting new technology.

Yet while AIDS activists are encouraged by progress towards a functional cure, they have sent an organizational sign-on letter to Sangamo regarding its development plans. Although the company states that it is meeting an unmet need with these newer trials, activists are concerned that Sangamo is not addressing a population of people with HIV who have not immunologically responded to traditional antiretroviral treatment.

Although the prior Phase 1 trials showed significant immunological improvement  indicated by CD4 cell gains in this population, the recent announcement said nothing about the volunteers in these trials. Activists stated that Sangamo has an “ethical obligation…to continue to provide treatment to the participants in these trials," and encouraged the company “in the strongest possible terms” to continue development of SB-728-T for this particular population.

One anonymous participant in one of the Phase 1 trial commented, “I view it [the zinc finger technology] as salvage therapy, or at best an immune enhancement for many of us who are at serious risk of getting sick. My own T-cells climbed to 900 after never having gotten above 200, and now they are around 550. Some mechanism for continuation of therapy for trial participants would be good for the company's reputation and for those running on empty.”

(Disclosure: Author Matt Sharp was also a participant in one of the early SB-728-T, as described in a previous article.)

In regards to immunological non-responders, University of Pennsylvania clinician and study investigator Pablo Tebas stated, “This is an area of significant need for good clinical and translational research. We need to evaluate systematically interventions to address this issue, without preconceived ideas of what will work or what will not work, as nobody really knows what the underlying cause of this problem is.”

Until a dialog between Sangamo and AIDS activists occurs, the question of how to improve treatment for immunological non-responders remains unanswered. “I’ve wondered myself what the next step is," said the anonymous trial participant. "I’m surprised that they are not looking down the road...I can only guess they are not thinking about repercussions.”

1/17/12

Source

Sangamo BioSciences. Sangamo BioSciences Announces Initiation of Two New Phase 2 HIV Clinical Trials. Press release. January 9, 2012.