Two recent data read-outs for clustered regularly interspaced short palindromic repeat (CRISPR) based therapies have recently led to shares sinking in three of the leading CRISPR-based therapeutics companies that have assets in clinical development. In the last month, the share prices of Intellia (-14%), CRISPR Therapeutics (-17%) and Editas (-40%) have all experienced rapid declines as investors became uneasy about the technology following disappointing data read-outs from two clinical trials. The Phase I/II BRILLIANCE trial and the Phase I CARBON trial are investigating assets being developed by Editas and CRISPR Therapeutics respectively.

The first data read-out from BRILLIANCE concerns the investigation of EDIT-101 in the treatment of CEBP-related retinal degeneration, which failed to demonstrate significant improvement compared to the control across a variety of visual improvement metrics, in a small number of patients across two different doses. In a recent press release, Editas focused on the ‘efficacy signal’ demonstrated in the mid-dose cohort and suggested that EDIT-101 is biologically active and provides potential clinical benefit, although the low and mid-dose cohorts failed to demonstrate statistically significant benefit compared to the control.

Despite failing to demonstrate clear efficacy so far in this Phase I/II trial, the small number of patients in this study and potential for further dose optimisation means it is too early to write this agent off. In addition, the company boasts a diversified clinical programme, utilising two distinct CRISPR nucleases across multiple therapeutic areas.

The second data read-out that has spooked investors is from the Phase I CARBON trial investigating CTX110 in the treatment of relapsed or refractory CD19+ B-cell malignancies with CRISPR Therapeutic’s ‘off-the-shelf’ CAR-T cell therapy. Despite positive results reporting comparable response rates to approved autologous CAR-T therapies on an intent-to-treat basis and a positively differentiated safety profile, the release of this data sparked unease in the markets.

This unease is based upon the question marks over the durability of the allogeneic CRISPR drug, in essence how long the cells remain in the patient’s body, and the smaller proportion of patients who had a complete response rate after six months because of lower durability. The three approved CAR-Ts for large B cell lymphoma have six-month complete response rates between 29–40%, while 21% had a complete response in the CRISPR trial. Despite this, the data are still premature and the positively differentiated safety data may mean that CTX110 is the safest CAR-T therapy yet, which may allow it to occupy a specific therapeutic niche.

Despite pessimism from the markets, GlobalData predicts that CRISPR-based therapies still have a promising future. This is predicated on the power of gene-editing technology, the diversity of the therapeutic areas being targeted, the unmet clinical needs and the potential for curative outcomes. Further patience may, however, be required for optimising the delivery and usage of CRISPR-based therapies.

Cell & Gene Therapy Coverage on Pharmaceutical Technology supported by Cytiva.

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