Does a setback for one gene editing biotech carry consequences for the rest of the fast-growing field? That's the question investors faced Thursday following the presentation of underwhelming trial results from an in vivo genome editing study conducted by Sangamo Therapeutics.
Shares in several other gene editing-focused companies slumped, suggesting the setback for Sangamo spurred fresh caution regarding the prospects for these emerging drugmakers to translate scientific breakthroughs into clinical advances.
While gene therapy as a whole has become more established — one gene replacement treatment for an inherited disease is approved in the U.S. — gene editing drug development remains more nascent. When new concerns or worries crop up, the subsequent market reaction can affect the entire sector. Publication of a pair of studies that raised questions on CRISPR gene editing's effect on cancer risk, for instance, triggered a short-lived market sell-off.
On Thursday, it was news on an older gene editing technology, called zinc finger nucleases, rather than CRISPR, that led to the latest stock market retrenchment for gene editing biotechs.
Sangamo's testing of its zinc finger nuclear approach in two rare genetic disorders known respectively as Hunter and Hurler syndromes is actually the first study in humans of in vivo gene editing.
Yet one study's early data, unveiled at this year's World Symposium, disappointed, sending Sangamo stock down more than 30% and weighing on shares of its gene editing peers.
Sangamo setback pressures gene-editing stocks
|Stock market reaction on Feb. 7*
*Rounded, measured versus closing price Feb. 6
Treatment with Sangamo's gene editing therapy appeared essentially ineffectual in five patients, failing to spur significantly higher activity of an enzyme missing in patients with Hunter syndrome. Higher enzyme activity was seen in a sixth study participant, only for that effect to fade as the patient experienced a suspected immune response.
Without this needed enzyme, called IDS, Hunter syndrome patients experience toxic buildup of a cellular waste product called glycosaminoglycans, or GAGs. After 24 weeks, urine GAG levels did not show a meaningful change in the six patients.
Sangmo acknowledged the results fell short of its hopes.
"While I'm very pleased that we are able to present preliminary evidence of a remarkable scientific achievement, I have a more realistic view of whether this first generation of [zinc finger nucleases] may accomplish everything that patients need," said Sangamo CEO Sandy Macrae on a Thursday call with investors.
The biotech is hopeful that higher enzyme activity could be spurred by a higher dose of its treatment, and awaits more data on how small increases in IDS enzyme levels translate into patient outcomes.
"We want to be clear that we too look on the low- and mid-dose cohorts and think it is unlikely that that is sufficient for a clinical benefit," Macrae said.
Sangamo also reported results from another in vivo genome study in patients with Hurler syndrome that the company said give it confidence in its zinc finger nuclease approach.
Sangamo is the chief pioneer of zinc finger nuclease-based gene editing. Many more biotechs, however, are exploring the potential of CRISPR-based gene editing, both in and out of the body.
Three of the most prominent — Editas Medicine, CRISPR Therapeutics and Intellia Therapeutics — all felt the effects of Sangamo's setback in share price declines.
Steven Seedhouse, an analyst at Raymond James, pointed out in a recent investor note that zinc finger nucleases have been studied as a gene editing approach for significantly longer than CRISPR-based editing.
"Despite that lead time in development, [zinc finger nucleases] still didn't work in the first in vivo iteration," Seedhouse wrote. "That adds a layer of clinical translation risk for CRISPR/cas9 that, if it wasn't completely apparent before, should be apparent now."
CRISPR biotechs, and investors in those companies, will soon have to grapple with how those risks play out in the clinic.
Editas Medicine is set to begin a Phase 1/2 in vivo study of its gene editing therapy EDIT-101 in patients with Leber congenital amaurosis 10, an eye disease that leads to blindness in childhood.
CRISPR Therapeutics, meanwhile, has begun along with its partner Vertex Pharmaceuticals a similarly early study of its gene editing candidate CTX001 in Europe, and has had an Investigational New Drug application accepted in the U.S.