August 7, 2024 | Companion diagnostics (CDx) have revolutionized the treatment of cancer by helping to improve the safety and tolerability of targeted drugs—a key feature of precision medicine. The U.S. Food and Drug Administration (FDA) has to date approved nearly 180 CDx, many for rare diseases but only four of those outside of oncology, according to Jai Pandey, Ph.D., global device regulatory head for in vitro diagnostics (IVD) and digital health at Sanofi.
What CDx has done for many patients with cancer and a handful of non-oncology rare diseases is poised to expand significantly to a slew of conditions of both the orphan variety and more common cardiovascular, neurological, infectious, and autoimmune diseases, he predicts. These biomarker-oriented tests are designed to help identify individuals most likely to benefit from a particular treatment or at risk of serious side effects and to monitor their therapeutic response.
The development of companion diagnostics, since the first one was approved by the FDA in 1998 (HercepTest), has always been a complex business, says Pandey. It is made even more byzantine when a global assay development strategy is being pursued, most especially for non-oncology indications where there is no specific regulatory guidance lighting the way.
For conditions outside oncology, global CDx developers must nonetheless take several regulatory considerations into account to ensure the safety and effectiveness of the devices, as Pandey will cover in detail at the upcoming Next Generation Dx Summit being held in Washington, D.C. The critical issues here include the governing regulatory authorities across geographies as well as CDx classification, clinical and analytical validation, and labeling.
One challenge is the “misconception” that antigen tests don’t qualify to serve as companion diagnostics, says Pandey. Indeed, they can, and therefore need to be developed as such. “This needs to be kept in mind when antigen testing is being used for patient selection.” Equally important, when it comes to CDx for rare diseases, is to choose the right central lab or IVD manufacturer to partner with, he adds.
Guidance documents on CDx—where they exist in the U.S., EU, Japan, and China—are focused on oncology because until recently almost all such devices had intended oncology applications, says Pandey. The added challenge in the EU is that it encompasses 27 member states, making it difficult for CDx developers to harmonize their testing approach to support a clinical trial and subsequent regulatory submission.
The list of FDA-cleared or -approved CDx includes only four devices for non-oncology diagnostic purposes—three for inherited blood disease and one for obesity.
These indications likely are the first non-oncology tests due to a combination of factors, he says, including the need for personalized treatment of the conditions and the availability of predictive biomarkers to signal their presence, Pandey says. For hemophilia, the development of CDx tests were “driven by the need to improve patient outcomes and understand genetic variations in terms of response to certain treatments.”
The oncology-specific guidance is better than nothing at all, but not sufficient for the nuances unique to other types of diseases, he says. One big reason a non-oncology-specific guidance would be useful is so rare disease drug developers know which assay will become the CDx for their therapy product, which in the cancer field is generally known from the outset. Experience in developing CDx for non-oncology indications is also limited, making guesswork out of which biomarker or modality may become the basis of a CDx.
It is now well appreciated that precision medicine approaches can improve patient outcomes, especially in non-oncology disease areas, Pandey continues. CDx has proven to be a viable means to boost the efficiency of drug development efforts as well as improve the success of costly clinical trials and, ultimately, is expected to reduce healthcare costs.
CDx devices might variably identify the most appropriate treatment for patients based on their genetic, molecular, or other specific characteristics, he notes. But most of the anticipated growth in the non-oncology arena is around gene therapies for rare diseases, although the genetic biomarkers for these conditions tend to be “not very well established” at present for predicting treatment effectiveness.
That’s one reason why collaborations between drugmakers and CDx developers are less popular outside of the oncology space, says Pandey. It is also tricky for pharma companies to choose a partner with all the right stuff—meaning, a central lab or IVD manufacturer with broad technology expertise that can also deal with all the therapeutic complexities and regulatory challenges and have the global capabilities for implementation and clinical data generation.
It’s a tall order with a limited number of viable candidates, particularly when it comes to rare diseases, he says. Yet outside of oncology, “that’s the most prevalent disease type where you may need to develop a precision medicine approach.”
Most of the drugs currently advancing through clinical trials are diagnostic-dependent and they are also focused largely on non-oncology areas, Pandey says, citing the “increased recognition of the importance of precision medicine” in improving treatment efficacy and patient outcomes. CDx test development for cardiovascular diseases, where for example troponins are being explored alongside heart medicines, has been gaining traction.
In the realm of neurological disorders, biomarkers (e.g., tau and amyloid) are being developed for identifying Alzheimer’s patients who are more likely to respond to certain treatments, he adds. Other therapeutic areas of note for CDx development are infectious diseases (e.g., monoclonal antibodies and single-pathogen agents) and autoimmune diseases (e.g., cytokines and chemokines).
Pandey says he anticipates that the landscape for CDx development beyond oncology will be seeing significant growth in coming years as more biomarkers are discovered and validated for use in a variety of therapeutic areas. “This expansion is being driven by several factors, including advancements in proteomics and point-of-care and at-home testing technologies that are enabling identification of new and clinically relevant biomarkers and facilitating test-and-treat approaches for rare disease patients.”