13. SB-913

DNA
Sangamo's ZFN-based therapy SB-913 failed to move the needle in the phase 1/2 CHAMPIONS study involving patients with the rare genetic disease mucopolysaccharidosis type II, or Hunter syndrome. (LionFive/Pixabay)

SB-913
Indication:
mucopolysaccharidosis type II
Sponsor: Sangamo Biosciences

Sangamo Biosciences has been working on its zinc finger nuclease (ZFN) gene-editing platform for many years, long before the emergence of rival method CRISPR, but early readouts from trials haven’t been encouraging.

Back in February, shares in the biotech were hit hard after its lead ZFN-based therapy SB-913 failed to move the needle in the phase 1/2 CHAMPIONS study involving patients with the rare genetic disease mucopolysaccharidosis type II (MPS II), or Hunter syndrome. It was a big letdown in the first trial to produce data with in vivo genome editing in humans.

The ZFN approach involves making cuts in the DNA of cells so as to allow the insertion of a new sequence—in this case a gene coding for an enzyme called IDS that is deficient in MPS II.

Sangamo said at the time that it may have to switch its attention to a second generation of the ZFN technology in the hope that it would have greater potency, and if that is the case it could result in a sizable delay to its in vivo gene-editing programs.

It’s since confirmed that no additional patients will receive first-generation ZFNs, and its next in vivo genome-editing clinical trial is expected to be started by year-end 2020.

In five of six patients enrolled in the CHAMPIONS trial, SB-913 wasn’t able to show either an increase in the IDS enzyme or a reduction in glycosaminoglycans, which accumulate with inadequate IDS levels and cause harm, including organ damage, in MPS II.

The sixth patient—who received the highest dose of SB-913—did have a transient increase in IDS that fell away after six weeks, which Sangamo attributed to the development of a mild transaminitis thought to be linked to an immune response. The increase gave some comfort to the company, which said it intended to test the high dose in another three patients.

There’s been no update on the program in the interim, but that may occur during Sangamo’s R&D day scheduled for Dec. 17.

In the meantime, Sangamo has been talking up the potential of its gene therapy programs in hemophilia A and Fabry disease and ZFN technology in ex vivo gene-editing applications like ST-400, its thalassemia and sickle cell disease treatment.

13. SB-913