Regulatory support, big pharma interest will boost precision medicine for cancer

New Delhi: With renewed support from regulatory authorities and interest from big pharma, additional resources are becoming available for validating and developing more refined and accurate biomarker testing protocols for cancer, which will fuel further development and translate into accelerated progress in precision medicine approaches, says leading data and analytics company GlobalData.

The first accelerated approval for a tumor-agnostic drug was granted to Merck’s checkpoint inhibitor ‘Keytruda’ by the US Food and Drug Administration (FDA) in May 2017. This approval was seen as groundbreaking at the time and has contributed to a shift from consideration of tumor classification by tissue specificity, to that of biomarker-defined types, independent of tissue of origin.

Fern Barkalow, PhD, Oncology and Hematology Director at GlobalData says: “By eliminating the tissue restriction of tumor type, this approach may serve to usher in a new chapter in precision medicine. However, the tissue-agnostic approach is not without issues to be considered. Keytruda was granted accelerated approval based on the results of five non-randomized, single-arm studies. Considering the nature of the patient population, which harbor rare mutations in refractory cancers, this type of trial design is considered acceptable for conditional approval status.

“The fact that randomized, controlled trials are not entirely feasible in this setting does, however, raise the issue of how to approach trial design for future tumor-agnostic studies. Many of these rare mutations occur in recurrent settings or in tumors for which there is no standard of care that could be used in the control arm. Other issues that warrant examination include how to best choose and evaluate disease endpoints across heterogeneous cancer types.”

FDA acknowledges that introduction of newer approaches to drug approvals requires the development and support of additional technologies and processes for data collection and review. GlobalData believes that increased adoption of the use of real-world evidence during the pre-approval and post-marketing phases could serve to facilitate drug approvals as well as market uptake in this setting.

In May this year, the FDA granted fast track priority review to larotrectinib for NTRK fusion-positive cancers. The drug is under development by Loxo, which recently partnered with Bayer. In July 2017, the FDA granted orphan drug designation in the tissue-agnostic setting for NTRK-positive tumors to a competing drug, Ignyta’s entrectinib.

Barkalow concludes: “Support from regulatory authorities and interest from big pharma will increase the likelihood of success in the tissue-agnostic setting. Increased biomarker testing, coupled with tissue-agnostic trials such as TAPUR and NCI-MATCH, designed to study responses for different biomarkers across various tumor types, will provide data to help expand the potential populations of patients available for treatment. In addition, continued investment by large pharma in the candidates under development by small companies, similar to Bayer’s partnership with Loxo and Roche’s acquisition of Ignyta, will serve to fuel further development and translate into accelerated progress in precision medicine approaches.”