Chemo drug helps HIV patients respond to Sangamo gene therapy

By Deena Beasley (Reuters) - Treating HIV patients first with a chemotherapy drug improved their response to an experimental gene-modifying technique for controlling the virus, according to Sangamo BioSciences. The company presented new data from a small early-stage trial of its treatment, SB-728-T, on Thursday at the Conference on Retroviruses and Opportunistic Infections in Boston. Shares of Sangamo were up 17 percent at $22.92 in late trading on Nasdaq. Shares of the Richmond, California company have gained about 67 percent so far this year. On Wednesday, the New England Journal of Medicine published data from an earlier trial showed that Sangamo's strategy of genetically modifying cells from people infected with HIV could become a way to control the virus that causes AIDS without using antiviral drugs. "Sangamo's HIV 'suppression' is promising, but very early and far from a 'cure,'" RBC Capital Markets analyst Michael Yee said in a research note. "This is very early study for technology and safety validation." The technique is designed to disrupt a gene, CCR5, used by the human immunodeficiency virus to infect T-cells, the white blood cells that fight viral infections. A patient's cells are removed and processed to alter the DNA that codes for the CCR5 receptor. The altered cells are multiplied and tested, then infused back into the patient. The results presented on Thursday show that increasing doses of the chemotherapy drug Cytoxan, or cyclophosphamide, before infusion with SB-728-T led to an improvement in both growth of the genetically modified cells and an increase in total CD4 immune system cells, which otherwise would be a target for HIV, according to Sangamo. Two of three patients treated with the highest Cytoxan dose have remained off of antiretroviral drugs for several weeks with detectable, but stable, levels of HIV in their blood, the company said. In all, nine patients received Cytoxan to augment their treatment. Cytoxan, made by Bristol-Myers Squibb, is used to reduce the number of T-cells in the body, which then rapidly repopulate once the drug is discontinued. The aim is to allow SB-728-T to be infused as new T-cells are growing in the body. Cytoxan is generally used to enhance effectiveness of bone marrow transplants in cancer patients and as therapy for autoimmune diseases. The gene editing technique behind SB-728-T seeks to mimic the resistance to HIV observed in the small number of people who have inherited CCR5 mutations from both parents. Sangamo has also been carrying out clinical studies in HIV patients who have one copy of the natural mutation. So far, the company has used a deactivated virus to deliver its gene-modifying technology to patients but said it will shift to a new method using messenger RNA to deliver the cell-altering proteins. Messenger RNA is a single-strand molecule that carries information telling cells which proteins to make. When a virus is used to deliver gene therapy, patients develop antibodies, making them immune to further treatments. By using messenger RNA, patients can be re-treated with SB-728-T if needed, said Sangamo spokeswoman Elizabeth Wolffe. Sangamo said it has expanded the Cytoxan preconditioning study to determine the right dose of the chemotherapy. It then plans to treat an additional 12 subjects, using the new messenger RNA delivery method, this year. "If those data are positive, plans are to move forward with pivotal trials with a pharma partner," said Sangamo Chief Executive Officer Edward Lanphier, referring to efforts to sign on a bigger drugmaker to help with funding. He did not give details on whom Sangamo might approach. Sangamo is testing its "gene editing" strategy to develop therapies for a number of diseases, including inherited illnesses such as hemophilia, sickle cell disease and Huntington's disease. (Reporting By Deena Beasley; Editing by Michele Gershberg, Jonathan Oatis and Cynthia Osterman)