Sangamo Therapeutics has posted lackluster data from a phase 1/2 trial of genome-editing therapy SB-913. The treatment failed to have the hoped-for effects on patients with the rare disease MPS II, causing investors to drive Sangamo’s stock down 30%.
SB-913 uses Sangamo’s zinc finger nuclease technology to make cuts in the DNA of certain liver cells and insert a functional copy of the IDS gene, which encodes for an enzyme that patients with MPS II lack. If SB-913 raises levels of the enzyme, patients may be able to break down glycosaminoglycans (GAGs) that would otherwise accumulate and cause harm including organ damage.
The interim phase 1/2 data results contain scant evidence that SB-913 can live up to that billing. In five of the six patients enrolled in the study, IDS activity and GAG levels scarcely changed in the 24 weeks following administration of SB-913.
Subject 6 is the exception that has given Sangamo some cause for optimism. The patient, one of two subjects to receive the highest-tested dose of SB-913, experienced rising IDS for the first six weeks, culminating in the level of the enzyme hitting 50 nmol/hour/mL. That is well below the normal range, which starts at 82 nmol/hour/mL, but well up on the sub-10 nmol/hour/mL baseline figure.
The subject's IDS levels fell away after week six, which Sangamo attributed to the development of a mild transaminitis thought to be linked to an immune response. At the last count, the patient’s IDS level was at 14 nmol/hour/mL.
In other contexts, the performance of subject 6 could be seen as disappointing. But given the lack of IDS or GAG activity in the other five patients, the temporary spike in the level of the enzyme in the final subject represents a possible lifeline for the study. Buoyed by the finding, Sangamo plans to test the high dose of the genome-editing therapy in another three patients. In the longer term, Sangamo is looking to its second-generation technology, which could be in the clinic this year, to boost efficacy.
The effect, or lack thereof, of SB-913 on the first two patients enrolled in the high-dose cohort has tempered optimism about the likelihood of the additional subjects responding strongly to the drug. Shares in Sangamo closed down more than 30% following news of the interim results.
Sangamo’s struggles have contributed to a tricky time for gene editing and therapy startups. In recent months, biotechs working with CRISPR and other genetic technologies have suffered stock drops as events have dented confidence in the hyped approaches. Some biotechs will survive the waning of the hype cycle and may go on to deliver breakthrough drugs. But, as Sangamo has found, life at the cutting edge of biology is tough.