Xconomy San Francisco — The first U.S. trial of a gene-editing medicine in humans isn’t going well. Sangamo Therapeutics (NASDAQ: SGMO) reported Phase 1 results this morning for its treatment for Hunter syndrome, a rare genetic disease. While relatively safe, the treatment, known as SB-913, did not seem to help patients much, based on measurements of proteins in their blood and urine that are meant to show that the treatment is working. Sangamo shares were down more than 35 percent, to $7.75, in midday trading. The study, known as CHAMPIONS, is testing three doses of SB-913 across six patients. It’s a tiny sample size, but in the new field of gene-modifying therapies, incremental updates from small trials are followed with outsized interest. With Hunter syndrome, also known as mucopolysaccharidosis type II (MPS II), children are born without the ability to produce an enzyme called iduronate-2-sulfatase (IDS). IDS normally breaks down cellular waste—proteins called GAGs—but without enough IDS, GAGs accumulate and can cause cognitive deficits, skeletal deformities, and organ damage, sometimes leading to an early death. Instead of infusing replacement IDS into a patient, which is what current treatments do, the goal of a genetic medicine is to reprogram a patient’s liver cells to produce the enzyme within a normal range. Sangamo, of Brisbane, CA, reported even earlier results for the study in September, with mixed results. The company’s report today focused on four patients, two each in the midrange and high doses. In the two midrange patients and one high-dose patient, SB-913 did not boost IDS levels in the blood past the baseline range after 24 weeks. Another high-dose patient got a more significant boost but it was short-lived, perhaps due to an immune system reaction against the drug’s delivery mechanism—a viral vector known as AAV-6 that ferries the gene-altering components into cells. After four months, the patient was hospitalized for a hernia, which was unrelated to the drug, Sangamo reported. Sangamo would also like to see its treatment reduce levels of GAG proteins in patients’ urine. After 24 weeks, the study showed “no meaningful change,” Sangamo reported. Three more high-dose patients are in the study but have not been on the treatment long enough to collect results. Sangamo is using its own proprietary gene-editing technology, called zinc finger nucleases. The report of a potential immune reaction against the viral vector is important to note, not just because this is the first look at results from gene editing inside humans, but also that AAV vectors are widely used in gene therapy, another genetic manipulation technology that has made more progress. So far they haven’t caused dangerous unintended problems. But experts have raised concerns about the safety of AAV vectors when used at high doses. Sangamo CEO Sandy Macrae told Xconomy in September that the AAV-6 vector used in SB-913 has never been inside humans before, and that Sangamo has designed its study to “prudently” escalate into higher doses. All the patients in CHAMPIONS are also taking enzyme replacement drugs, the standard of care for Hunter syndrome. For a clearer sense of how SB-913 works, Sangamo is also testing patients who have been weaned off their enzyme replacement. Analysis of those patients will come later in the year, Sangamo said. The firm is also working on a second-generation version of SB-913, which it hopes can increase efficacy. It could enter clinical testing later this year. In addition to the Hunter syndrome patient data, Sangamo today reported extremely early results—three patients’ worth—from a trial to treat Hurler syndrome, or MPS I. The next-generation zinc finger technology could be used to treat MPS I, as well.
Cambridge Therapeutics ’ landmark phase I trial of its gene - editing therapy for Down syndrome has failed to show sufficient improvement , according to measurements of proteins in the blood and urine of patients . There was one initially encouraging trial , but this proved temporary . SB-913 is used to treat the rare genetic disease that causes children to be born without a certain enzyme , which can lead to cognitive and skeletal problems , damaged organs and even premature death . Sangamo is trialling two doses of SB-913 on six patients . The treatment has been deemed relatively safe for use .