- Several biotechs working on gene-editing therapies saw their stocks fall Monday afternoon as a pair of studies stoked concerns that an integral technology used in this drug development area may increase the risk of cancer.
- Both studies focused on a gene responsible for repairing and destroying cells with damaged DNA. Together, they found the CRISPR-Cas9 system — which research has shown can help cut out and sometimes replace stretches of problematic DNA — is most effective in cases where the gene, called p53, is dysfunctional. In other words, the tech works best in cells that are at a predisposition to become cancerous.
- Against those conclusions, shares of the Swiss biotech CRISPR Therapeutics dipped nearly 13% by market's close. Intellia Theapeutics, Sangamo Therapeutics and Editas Medicine shares also ticked down, though in the mid to high single-digits.
The industry has high hopes for CRISPR-Cas9. Just last month, three researchers took home one of The Kavli Foundation's prestigious awards for their work with the tech. The award, which comes with a $1 million prize, was given "for the invention of CRISPR-Cas9, a precise nanotool for editing DNA, causing a revolution in biology, agriculture, and medicine," according to the foundation.
Hype around revolutionary advancements rarely goes without scrutiny, however. For CRISPR/Cas9, the biggest concern has been whether editing human DNA in this way is safe. In one example, shares in CRISPR Therapeutics and its partner Vertex Pharmaceuticals slid in value after the Food and Drug Administration placed a clinical hold on the companies' ex vivo gene-editing therapy for sickle cell disease.
Monday's studies, published in the journal Nature Medicine, fanned the flames of skepticism even further — at least for biotech investors.
Nearly half of all tumor cells lack the p53 pathway, the University of Cambridge noted in a June 11 statement about the findings from one of the studies, led by researchers from the school as well as Sweden's Karolinska Institutet. Through their investigations, the researchers found it was much easier to get CRISPR/Cas-9 to work in cells that didn't have the pathway, including tumor cells.
As a result, the tech showed a "strong selection" for cells with defective p53.
"Although we don't yet understand the mechanisms behind the activation of p53, we believe that researchers need to be aware of the potential risks when developing new treatments," Jussi Taipale, a study author and professor at the Karolinska Institutet, said in the statement. "This is why we decided to publish our findings as soon as we discovered that cells edited with CRISPR-Cas9 can go on to become cancerous."
The other study, led by scientists from Novartis Institutes for BioMedical Research, came to similar conclusions — namely that functional p53 inhibits CRISPR/Cas9.
"Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in," human pluripotent stem cells, the authors wrote.
Despite stock selloffs, the biotechs that built their businesses on these kinds of platforms didn't seem too rattled by the new findings.
"We have seen no evidence of any of these effects in our studies and do not believe the theoretical risks described in these papers apply to CRISPR Therapeutics' programs," the company wrote in an emailed statement to BioPharma Dive.
"We apply CRISPR for gene disruption or high-efficiency gene correction, neither of which are the focus of these reports. In all cases though, we seek to evaluate potential risks carefully and assess thoroughly as we advance our programs to the clinic."
Intellia largely echoed those sentiments, writing in a separate email to BioPharma Dive that it "has not found this type of effect in any of our in vivo studies using our lipid nanoparticle delivery system, including our 52-week study of successful TTR knockdown in mice and our ongoing studies of non-human primates."
Intellia also said that, for its ex vivo work, it had not seen the type of toxicity or tumorgenicity reported in the Nature studies.
Editas, meanwhile, noted its own research has yielded different findings about p53.
"[W]e can now achieve much higher targeted integration rates and gene correction without suppressing p53 than the authors of this paper saw in their experiment. Thus, for making medicines, we do not believe p53 suppression is appropriate or needed to achieve high levels of gene correction," a spokesperson for Editas said in an emailed statement.
Sangamo, which is developing a different gene-editing technology known as zinc finger proteins, didn't immediately respond to a request for comment.