Companion diagnostics in cancer care: Collaboration is key for continued innovation

• The use of companion diagnostics has had a huge impact on the approach to cancer care in recent decades
• The development process for companion diagnostics brings valuable opportunities for innovation and collaboration, driving advancements while meeting complex regulatory challenges and requirements
• The value of companion diagnostics should not be underestimated in the future of precision medicine 

The concept of companion diagnostics is not new. The first companion diagnostic was approved more than 25 years ago when an optimized immunohistochemistry assay was developed during trials for the breast cancer drug Herceptin (trastuzumab).¹ The assay detected HER2 overexpression in tumors, meaning the patient population most likely to respond to the drug could be identified. The success of this innovative approach paved the way for a drug and diagnostic co-development model where a predictive biomarker assay is used to select patients most likely to respond to treatment.¹

Healthcare Transformers spoke to Trent Landon, Robert Loberg, and Helen Wu about why companion diagnostics are so important in cancer care, and how diagnostic and pharmaceutical partners can work together to innovate in this space.

Oncologists treating cancer patients need as much information as possible about a patient’s disease in order to make personalized treatment decisions, and companion diagnostics have proven to be essential tools for this. As defined by the U.S. Food and Drug Administration (FDA) they can:²

• Identify patients who are most likely to benefit from a particular therapeutic product
• Identify patients likely to be at increased risk for serious side effects as a result of treatment with a particular therapeutic product
• Monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness

Wu explains that this is an important improvement in care: “A lot of standard of care treatment is what I call untargeted treatment, such as chemotherapy. In this case, there are a lot of side effects, and a patient’s quality of life can be diminished.With targeted therapy, often the side effects are much less, and the response rate is much higher.”

 Landon agrees and believes companion diagnostics are critical within the healthcare industry. This is especially true in the oncology space, but there have also been developments in other indications such as ulcerative colitis, non-alcoholic steatohepatitis (NASH), and Alzheimer’s disease. He notes, “We’re finding more and more [biomarker] targets. Unique biomarkers that we can use to either enroll patients for the right program, to stratify the population to ensure that the arms of the trials are balanced, or to move patients who are in relapse into different programs based on their biomarkers. Companion diagnostics ensure that you put the right patient on the right drug, at the right time.”

By definition, a companion diagnostic requires a pharmaceutical treatment to work alongside. In many cases a targeted therapy can’t get approval without a companion diagnostic, so pharmaceutical and diagnostic companies typically collaborate to develop a clinically validated test. “If you have a companion diagnostic in the drug claim, the data generated by this collaboration demonstrates the  clinical utility of the companion diagnostic to identify the target population who may respond to the drug, rather than an unvalidated test where it’s not certain if the results are reliable. You can’t underestimate the power of a good relationship with the pharma partner throughout this process,” explains Wu.

 Landon agrees that the concept of partnership is really important: “We are acting as collaborators. For instance, when I work with an external pharma partner, a lot of times you can’t tell where one begins and the other ends. Scientists, bioinformatics, and legal are all talking to each other. It’s just this really collaborative effort. Developing a companion diagnostic takes five years, sometimes more, so we need to ensure that we’re on the same page and that we’re open, honest, and collaborative. Otherwise, it’s just not going to go anywhere.”

According to Landon, to innovate in the area of companion diagnostics, “larger pharmaceutical companies often rely on external sources for innovation, such as academic research or acquisitions, as they focus on scaling and operational excellence. Emerging biopharma start-ups, however, are driving much of the innovation in the field, making it essential for us to actively engage with these dynamic organizations.”

Loberg agrees that start-ups play a key role in the future of companion diagnostics: “The scientists who actually invent a technology, usually in an academic institution, might spin it out as a startup. So they’re very closely connected to the inventors, which adds an advantage because these are obviously very smart, very passionate people. They had the idea to begin with and can move very quickly bringing that innovation forward in an agile way than a big company can.” Where larger companies can help is by evaluating and recognizing innovation, and enabling the idea to move forward. He says, “When it’s the right therapeutic candidate, bring it in and help scale it to the extent where it can really have benefits in a global setting. This is a huge part of how innovation and technology feed into this whole paradigm of diagnostics and pharmaceuticals.”

Wu outlines how the core competencies of a larger company and a start-up can be complementary. “A small company can determine what the biomarker is, they can work with the pharma partner to show proof of concept and that the biomarker is actually predictive of response. Once that happens, pharma and diagnostic partners have the clinical and the regulatory expertise to complete pivotal trials, perform any  bridging studies required to the  original clinical trial assay, support a registrational trial, and submit for registration to health authorities. A smaller diagnostic company often doesn’t have the global reach for implementation world-wide. They may not have affiliate support in many different countries, and they certainly may not have the regulatory or clinical expertise.”

The requirement for regulatory knowledge and expertise is an area that has become increasingly important in recent years as global standards evolve. For example, in 2022 the European Union’s In Vitro Diagnostics Regulation (IVDR) introduced more stringent requirements on developers and manufacturers than the previous In Vitro Diagnostic Directive (IVDD).³ The IVDR is more complex, requiring more resources and longer review times. Additionally, countries can vary in their interpretation of IVDR requirements, meaning companies must carefully analyze local and regional laws.⁴

Landon says this makes for “a really challenging market right now.” He explains, “In Europe,  IVDR compliance regulations can cause pharma to re-evaluate their strategy, and every single country in Europe can have their own unique regulations. They’re working to standardize that like the FDA in the US, but it’s not going to be overnight. So I think having a strong regulatory and quality team that understands the global marketplace and understands the regulatory hurdles that are unique to each individual country is essential.”

“It’s really a lot of coordination with the pharma company and different branches of health authorities,” agrees Wu. “One for the diagnostic, one for the pharma, and coordinating all of that and understanding all the regulations throughout the globe. It’s complicated and it can take a long time to get the appropriate approvals. I think for a smaller company, this could be quite challenging, so it’s about making sure you have people with the right expertise.”

Within this difficult regulatory environment, there is pressure to demonstrate the value of companion diagnostics beyond the benefits to patients. Loberg believes the diagnostic community must continue to push for more efficient technologies to keep costs low, but also encourages providers to look at the totality of the cost of cancer care. “A companion diagnostic test could avoid a highly expensive drug being used in a patient that wouldn’t necessarily respond, or ensuring the right patients are getting the right drugs. It’s about rethinking the paradigm of where the value and the finances in totality occur for hospitals.”

Economies of scale can also come into play. “The more people are using it, the lower the cost of goods can become, as well as ensuring it gets to the most people globally,” says Landon, “From the data perspective, we need to show efficacy. The proof is in the pudding! So, making sure that the diagnostic is specific enough that it can ensure that the drug is successful, but also broad enough that it can reach the most ethnic groups across the globe.”

Comprehensive genomic profiling is a development that could overcome this challenge. Whereas most conventional companion diagnostics are aimed at detecting a single biomarker, with comprehensive genomic profiling it is possible to look at a broad range of biomarker mutations. “When you can have a test that will cover a lot of different biomarkers that will encompass many different companion diagnostics for a wide range of therapeutics, I think that makes sense for healthcare providers,” says Wu, “It makes sense for the patient too, because we all know that getting tumor tissue from the patient is not easy. The more that you can do with one piece of tissue the better, and it’ll be more cost-effective for the organization because there are different intended uses for it.  The detection of multiple mutations or gene signatures in a single test provides more information to clinicians and their patients to identify appropriate therapies. I think we’re all moving in the direction of comprehensive genomic profiling. It’s just a matter of time.”

With truly precision medicine becoming increasingly possible, Loberg believes diagnostics need to be front and center of this approach: “We are in a world where there’s going to be increasing pressure to provide more and more information using diagnostic tests to guide therapy, as well as to develop new therapies that have a better impact on patient lives. Diagnostic tests should not be an afterthought anymore. Diagnostic tests should be integrated into every clinical development plan from the beginning, for every molecule going through the pipeline, and considered throughout the entire development process. I believe it is that important to the future of cancer care.”