May 2012 Edition Vol.11, Issue 5

The Rise of Companion Diagnostics: A Step Towards Truly Personalized Medicine

The Rise of Companion Diagnostics: A Step Towards Truly Personalized Medicine

By Christopher P. Leamon and Mike A. Sherman

While therapeutic compounds are becoming more targeted to defined patient populations, the expectations for demonstrating benefit in these targeted groups are increasing. This is especially evident in the field of oncology, where there is a growing need for companion diagnostics (sometimes referred to as theranostics) to identify patients with a specific biomarker that is predictive of response.

The US Food and Drug Administration (FDA) recognized the need for companion diagnostics in recent draft guidance that outlines the agency’s preference for simultaneously approving a therapeutic agent with its companion diagnostic agent.1 On the heels of their publication came the approvals of a companion diagnostic to accompany Pfizer’s targeted lung cancer therapeutic, Xalkori® (crizotinib), and Roche’s personalized therapeutic for melanoma, Zelboraf® (vemurafenib). These approvals indicate both the value of companion diagnostics to guide therapy as well as the FDA’s support of their use.2

The Potential of Companion Diagnostics

Companion diagnostics have the ability to predict which patients will respond to therapy, and thereby improve patient outcomes and decrease healthcare costs. For patients with cancer, for instance, those that are identified as “not likely to respond” can quickly move on to other—perhaps more effective—therapies if they exist.

Furthermore, companion diagnostics help the healthcare system save costs by identifying the patient population that will most likely benefit from the therapy, and ruling out therapies that are not likely to be effective. This is especially important as higher-priced cancer therapeutics enter the market. An additional benefit can be realized by decreased costs related to managing side effects or hospitalizations due to unnecessary treatments.

Clinical studies have demonstrated that identifying patients with the presence of biomarkers or disease-specific therapeutic targets with a companion diagnostic can result in dramatically improved outcomes, even in difficult-to-treat disease indications. Xalkori’s approval, for example, was based upon two studies that demonstrated improvements in objective response rate (ORR), specifically 50% and 61%, in ALK-positive patients with late-stage, non-small cell lung cancer (NSCLC), which are extremely positive outcomes considering the majority of the patient’s had received prior chemotherapy.3,4 Previous studies have shown 10% response rates to second- and third-line chemotherapies in unselected patients with advanced NSCLC.3

By focusing on a select group of patients who will likely derive the most benefit from a therapy, overall efficacy should be greater, which would increase the likelihood of a drug’s approval. This approach also allows eligibility for certain regulatory incentives that streamline drug development, such as accelerated approval.

Considerations for Development

Clinical trials conducted with selected patient populations are also more likely to demonstrate efficacy. Such trials are often smaller in size due to the inclusion of only targeted patients, which often means the trials can be completed more quickly and at lower cost. For instance, if Endocyte’s folate receptor (FR)-targeted therapeutic agent, vintafolide (EC145), is evaluated only in a select group of patients that express the highest level of this biomarker (i.e., FR[++]—meaning that all lesions are positive for the receptor), the size of a Phase 3 trial gets reduced from approximately 600 patients to around 200 patients. In theory, this dramatic change to the design of the clinical trial should also increase the likelihood that the drug will demonstrate clinical efficacy.

Using a companion diagnostic in development may also increase the probability of clinical success, especially when used early, maybe even prior to development of the therapeutic itself. For example, the companion diagnostic can be used during the preclinical stage to confirm the expression and specificity of the target (i.e., biomarker), as well as the quantity or frequency of that target for a specific disease indication. Once confirmed, development of the therapeutic can then proceed. At Endocyte, for example, early on in drug development we confirm that the diagnostics are delivered specifically to diseased cells and not to healthy cells. This approach saves time and resources which may otherwise have been used to pursue a drug with a suboptimal target. Importantly, this approach de-risks the drug development process.

As defined by the FDA, companion diagnostics provide essential information related to the safety and efficacy of use of a therapeutic in patients;1 therefore, it is extremely important for the diagnostic tests to be confirmed as reliable, accurate, and clinically meaningful. In addition to reliability, payers have clearly expressed that a companion diagnostic must also have clinical utility in order to be reimbursable.5 Clinical utility is defined as the ability to demonstrate “evidence of improved measurable clinical outcomes, and the test’s usefulness and added value to patient management decision-making compared with current management without testing.”6

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