Rytelo: what flexibility did regulators accept, and why?

“Based on the literature provided by the Applicant and discussion with the clinical team, the life expectancy for patients with lower risk MDS (defined variously, but usually as low or intermediate-1 risk disease by IPSS) and ESA failure or transfusion dependency is > 5 years and carcinogenicity risk assessment is warranted for the intended patient population.”

“To address the carcinogenicity risk assessment of imetelstat, there will be separate Post Marketing Requirements (PMRs) for carcinogenicity assessments in the mouse and rat species.”

“No xenograft studies were conducted in MDS cells lines, and this was described by the Applicant as being due to the lack of MDS specific cell lines and mouse xenograft models.”

“Importantly though, many of the identified transcripts were not covered in the nonclinical toxicology studies due to lack of sequence homology in the toxicology species.”

“The rat data indicates that imetelstat is rapidly degraded (including in the bone marrow) but the resulting degradation metabolites have not been identified (e.g., no identification of N-1, N-2 etc. metabolites has been provided by the applicant).”