For genome editing technologies in drug development, the European Medicines Agency’s (EMA) executive director Guido Rasi said recently that it’s time to not just reflect on the challenges but also to exploit the opportunities to work together with industry and others toward treatments.
The comments, addressed to the EMA Committee for Advanced Therapies (CAT) and the Committee for Human Medicinal Products’ (CHMP) Pharmacogenomics Working Party’s (PGWP) expert meeting on genome editing, come as the number of scientific recommendations on advanced therapy classifications has risen from just a dozen in 2011 to 87 in 2016.
Academics from the Karolinska Institute in Stockholm to the National Center for Tumor Diseases in Heidelberg, Germany discussed the state of the art and outlook for genome editing and technologies, according to a report on the meeting.
“CRISPR offers the possibility for a more rapid and more specific generation of animal models, allowing for effective knockouts in genetically inaccessible models, simultaneous targeting of multiple genes and the possibility of biallelic modification,” Volker Lauschke from the Karolinska Institute said.
And though at the time of the expert meeting there were no clinical trials in the US or EU for CRISPR-Cas based products, Bernd Gänsbacher, a member of the EMA’s CAT, gave a high-level overview of the possible clinical applications of CRISPR-Cas: “either to repair/restore (fix or modulate ‘broken’ gene(s) to restore or preserve a healthy phenotype) or redirect/rewire (to program cells to carry out activities different from the normal state).”
Some are close to entering clinical development, he noted, as several non-clinical programs are ongoing, including those from academic sponsors and small developers. “He concluded his talk highlighting the importance of early dialogue with the Regulatory Authorities to address the current challenges with this novel and promising technology. This will facilitate the progress into clinical trials and the future marketing authorisation and access to patients at EU and international level,” the report said.
Industry also offered its perspective, with Bluebird Bio, Cellectis, Sangamo Therapeutics, Intellia Therapeutics, CRISPR Therapeutics and Editas Medicines presenting.
According to the report, CRISPR Therapeutics has “established and optimized an innovative CRISPR/Cas9 approach to achieve editing efficiencies in human primary HSPCs [Hematopoietic stem/progenitor cells] at clinical scale of greater than 80%. This high rate of editing was associated with robust HbF [fetal hemoglobin] expression following erythroid differentiation of edited cells from healthy donors and from patient samples, well into the range that may be clinically relevant.”
Safety is supported by no identified off-target editing after extensive next-generation sequencing at thousands of potential homologous sites or putative sites, CRISPR noted.
Meanwhile, off-target toxicity was identified in round table discussions as one of the major relevant unknowns.
“The group concluded that current scientific knowledge is far from fully understanding and interpretation of off-target findings, especially in genomic regions whose functions are unknown,” the report said.
The development of immunogenicity, “e.g. due to long exposure to the nuclease,” was also identified as a potential risk to be considered for genome editing treatments.
CAT monthly report of application procedures, guidelines and related documents on advanced therapies