South Korea has issued guidelines to monitor the side effects of the two approved CAR-T therapies – Kymriah (tisagenlecleucel) from Novartis and Carvykti (ciltacabtagene autoleucel) from Janssen. This will ensure a comprehensive database of adverse events including malignancies, if any in the local population, thereby ensuring patient safety in the country. However, regulatory focus on malignancy data might extend clinical trial timelines and increase costs for pipeline therapies, says GlobalData, a leading data and analytics company.

The Korean Ministry of Food and Drug Safety (MFDS) has recently mandated the reporting of any suspected adverse reactions, including T-cell malignancies, to the Korea Institute of Drug Safety and Risk Management.

This notification comes shortly after the US Food and Drug Administration (USFDA) announced the investigation of the globally approved six autologous CAR-T cell immunotherapies, after receiving reports of a few secondary cancer events.

Sasmitha Sahu, Pharma Analyst at GlobalData, comments: “This is in line with the USFDA’s action not to abruptly withdraw the approved therapies from the market. The continued access and careful monitoring will ensure the identification of any developing malignacy, thereby ensuring timely informed treatment decisions for the patients. The collected data can further be used to inform future research on CAR-T therapies.”

According to GlobalData’s Pharma Intelligence Center, while there is only one CAR-T therapy in Phase II and above pipeline in South Korea – anbalcabtagene autoleucel from Curocell, there are 217 CAR-T therapies in Phase II and above pipeline globally for various oncology indications.

Sahu adds: “The Korean regulatory agencies will now be more focussed on receiving expansive data regarding malignancies as well. This could mean extended clinical trial timelines and additional costs for the pipeline therapies. Altogether, this situation further builds up the uncertainty surrounding the approval of the pipeline CAR-T therapies.

“Moreover, companies with new CAR-T therapies that have already been approved in other major markets and trying to submit for approval in South Korea may also need to conduct post-marketing surveillance within the local populations on approval to assess the long-term safety and the risk of secondary malignancies.”

The USFDA, however, asserted that the benefits of the approved CAR-T therapies outweigh the risks while it continues the investigation. There was no similar assertion in the Korean notification.

Sahu concludes: “CAR-T therapies come with documented adverse events like CAR-T cell-related cytokine release syndrome and neurotoxicity but malignancies and death- related events were found to be minimal. While the prognosis for patients who have failed first-line therapies includes bleak survival rates, the availability of CAR-T therapies approved for second line treatment and beyond provides a ray of hope for improving survival rates. The outcomes of this monitoring are expected to bring in regulatory revisions for the approval of new CAR-T therapies to ensure access to safer therapies in South Korea.”