Transparency Submission

FDA Clearance: N/A

Rationale for Requested Change: As described in the treatment guidelines requests for BCEL-4, BCEL-5, BCEL-6, and BCEL-9, there is an abundance of evidence demonstrating the prognostic performance of Foresight’s MRD test in patients with LBCL regardless of PET-CT response and at multiple timepoints in patient care [2-11]. Although inclusion in guidelines typically occurs after sufficient evidence is available and tests are widely available, we believe there is a compelling case to be made for the inclusion of the Foresight CLARITY test in this next iteration of the NCCN guidelines. Given the growing body of data demonstrating the clinical utility of this assay coupled with recent changes in the payor reimbursement landscape, inclusion in guidelines represents a key and necessary step prior to the test becoming widely available, as described below. There is a critical shift in payor reimbursement market dynamics that complicates the paradigm of test availability preceding inclusion in guidelines. States operating in the Novitas Solutions (Novitas) Medicare Administrative Contractor (MAC), which includes Foresight Diagnostics, are awaiting the publication of the Novitas Genetic Testing for Oncology (L39365) Local Coverage Determination (LCD). This LCD was originally released and subsequently pulled in July 2023 and remains on an indefinite hold granted by CMS and is in the process of being redrafted as of 26 Jul 2024, per the latest update provided by Novitas. Based on the original draft of the LCD in July 2023 and discussions with Novitas as recently as June 2024, we anticipate that the LCD will require inclusion in the NCCN guidelines for a new test to be covered for reimbursement. This is concerning for several reasons, two of which are specifically outlined here: (1) Most critically, while we await the publication of this LCD and subsequent updates to coverage requirements, clinicians and patients do not have access the Foresight CLARITY test; and (2) Even upon publication, for patients and clinicians to gain access to the Foresight CLARITY test, the test must be covered by Novitas. This shift in requiring inclusion in guidelines as a precursor for reimbursement has created a chicken-and-egg scenario where it is not feasible to offer the test without coverage, and Novitas is unlikely to cover the test without guidelines inclusion. Securing inclusion in the NCCN guidelines will allow Foresight to pursue Novitas LCD coverage and make the Foresight CLARITY test widely available to physicians and patients. Although the Foresight CLARITY test is not currently available outside of clinical trials, the test is ready for a wider launch following approval of test codes, coverage, and reimbursement. The Foresight CLARITY test is already in use for prospective patient selection in clinical trials and Foresight Diagnostics is prepared to move rapidly towards making the test broadly available should the NCCN guidelines adopt this request. Foresight is currently conducting real-time testing in a fully automated CLIA-registered central laboratory in support of clinical trials in DLBCL, with the test having received IDE approval from the FDA in May 2024. Testing is being conducted with a <14-day turn-around time utilizing Foresight testing kits that are distributed to enrollment sites. Foresight’s laboratory director is also qualified to test in the states of California and New York, at their higher levels of regulatory requirements. The robust analytical performance of Foresight CLARITY as performed in our CLIA laboratory has been demonstrated by our IDE approval from the FDA, which included the data provided by Boehm et al. [1]. Importantly, the false positive rate is less than 1% and the LOD95 (limit of detection achieved in 95% of patients) is less than 1 part per million, at 0.66 parts per million, using a clinically practical amount of blood plasma and cell-free DNA. In addition, Goldstein et al. demonstrated a correlation between analytical performance and clinical performance [2]. Specifically, an LOD95 of 1e-6 was demonstrated to improve clinical detection of ctDNA-MRD compared to ctDNA-MRD testing with an inferior LOD95 [reference 2, slides 12 and 13]. While other MRD tests have demonstrated prognostic performance in a general context for DLBCL, the sensitivity of those tests has not yet been demonstrated to reach 1e-6 in a reasonable amount of blood plasma. This means that clinical performance of those emerging tests is unlikely to match the performance observed with the Foresight assay. However, this is not a concern for Foresight’s test in light of the robust analytical performance that has been demonstrated [1]. As a number of MRD tests are emerging, we believe that Foresight’s test has demonstrated both the robust analytical performance [1] and clinical performance [2-11] necessary for incorporation into clinical care. As such, we believe it is appropriate and in the best interest of patients for the BCEL-A guidelines to include ctDNA-MRD assessment using the Foresight CLARITY test.