Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals

Abstract

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

Luminal Extracellular Vesicles (EVs) in Inflammatory Bowel Disease (IBD) Exhibit Proinflammatory Effects on Epithelial Cells and Macrophages

“…Although known fecal (calprotectin) and serum (CRP) biomarkers used in IBD can correlate with macroscopic indices of inflammation, they provide no insights into which inflammatory pathways may be predominant in a given individual. Our present data suggest that EV content may reflect the transcriptional activity of their originator cells at inflammatory sites, making them a potential companion diagnostic for pathway-specific drugs 33 .…”

“…In addition, our demonstration of the stability of EV RNA in fecal samples is an additional important characteristic. These properties warrant EVs being examined as potential companion diagnostic for pathway-specific drugs 33 . Beyond their observational value, there is also emerging data on the potential to harness EVs as therapeutic mediators 34 .…”

Precision Medicines’ Impact on Orphan Drug Designation

“…We chose 2010 as a baseline as there was a 1.3‐fold increase in orphan drug designations over the previous year and the first year the FDA received >300 orphan drug designation requests, perhaps indicative of an increasing trend toward precision drug development approaches. Also, 2010 was the year prior to a marked increase in the proportion of NMEs receiving marketing approval that had also received orphan drug designation as well as the number of NMEs for smaller, molecularly defined, pharmacologically relevant subsets, primarily in oncology . We chose 2015 because we continued to see increases in both the requests for and the granting of orphan drug designations through 2015, and, at the time the analysis was initiated, it was our most recent year with complete data.…”

Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion Diagnostics

“…The use of a companion diagnostic during clinical trials has been indicated to provide an expedited process in addition to reduced costs through a guided selection of eligible patients. 148 Most of these tests have traditionally been performed in vitro through testing of genetic or protein markers from biopsy samples, such as Her2/Neu expression in breast cancer, 149 ALK rearrangements in nonsmall cell lung cancer, 150 and KRAS mutations in colorectal cancer. 151 The information gained from these tests has proven its utility, as patients who undergo a treatment that has a companion diagnostic have been demonstrated to have fewer grade 3 or 4 adverse reactions and a decreased rate of treatment discontinuation.…”