DRAFT — PREPARED BY CALDERWOOD & HARKNESS LLP — NOT FOR SUBMISSION
GENOME DX THERAPEUTICS INC. 4720 Torrey Pines Road, Suite 300 San Diego, CA 92130
[August __, 2024]
Cascade Fiscal Intermediaries, LLC
Attn: Dr. William Hargrove, MD, FACP
Medical Director, Molecular Diagnostics Coverage Determinations
Attn: Sandra Phu
LCD Analyst, Genomic Diagnostics 2800 SW Moody Avenue, Suite 500 Portland, OR 97201
Re: Request for Local Coverage Determination — OncoPrecise GXP-47 (Genome Dx Therapeutics Inc.) — MolDx Program
Dear Dr. Hargrove and Ms. Phu:
I. PURPOSE OF THIS REQUEST
On behalf of Genome Dx Therapeutics Inc. ("GDT"), I am writing in my capacity as Co-Founder and Chief Executive Officer to respectfully request that Cascade Fiscal Intermediaries, LLC ("CFI"), in its capacity as the Medicare Administrative Contractor ("MAC") for Jurisdiction E (which includes the State of California, among other states), initiate a local coverage determination ("LCD") proceeding for GDT's proprietary laboratory-developed test ("LDT"), OncoPrecise GXP-47.
This LCD request is submitted under the Molecular Diagnostic Services ("MolDx") program administered by Ridgeline Administrative Services, LLC ("RAS"). Accompanying this letter, GDT is pleased to enclose its MolDx Technical Assessment Dossier (Version 1.0) for OncoPrecise GXP-47, which has been prepared for review by Dr. Catherine Embry, MolDx Technical Assessment Director, at RAS (1600 Hampton Street, Suite 700, Columbia, SC 29201). GDT respectfully requests that CFI forward the enclosed Dossier to Dr. Embry for technical assessment review, or, if CFI prefers, GDT will submit the Dossier directly to RAS concurrently, as appropriate under applicable MolDx program procedures.
Through this submission, GDT is requesting Medicare coverage and a favorable coverage determination for OncoPrecise GXP-47 as a medically reasonable and necessary diagnostic test within the meaning of Section 1862(a)(1)(A) of the Social Security Act. As detailed in the sections that follow, GDT believes that OncoPrecise GXP-47 meets or exceeds the evidentiary standards required for a positive LCD under the MolDx program, including with respect to analytical validity, clinical validity, and clinical utility. GDT further presents health economic evidence demonstrating that the test generates net cost savings for the Medicare program by enabling more targeted and effective treatment selection for patients with advanced non-small-cell lung cancer ("NSCLC").
GDT appreciates CFI's and RAS's dedication to rigorous, evidence-based coverage determinations for molecular diagnostic tests, and welcomes the opportunity to engage fully with CFI and RAS throughout the LCD review process, including participation in any open meeting, Contractor Advisory Committee ("CAC") review, or public comment process.
II. COMPANY OVERVIEW — GENOME DX THERAPEUTICS INC.
Genome Dx Therapeutics Inc. is a Delaware corporation headquartered in San Diego, California, with Employer Identification Number (EIN) 83-2947156. GDT was founded in 2018 by Dr. Anisha Raval and Dr. Marcus Yuen with a mission to develop and commercialize next-generation sequencing ("NGS")-based genomic tests that deliver clinically actionable, personalized information to oncologists and their patients.
GDT is a clinical-stage molecular diagnostics company that specializes in the development, validation, and commercialization of NGS-based genomic profiling assays for oncology applications. The company's proprietary OncoPrecise platform integrates advanced RNA expression profiling with proprietary algorithmic scoring methodologies to produce composite biomarker indices that inform treatment selection across multiple solid tumor types.
GDT operates a single CLIA-certified, CAP-accredited reference laboratory located at its headquarters in San Diego, California. The laboratory's credentials are as follows:
• CLIA Certificate Number: 05D2187432
• CAP Accreditation Number: 9074821
• National Provider Identifier (NPI): 1902847365
• Laboratory Address: 4720 Torrey Pines Road, Suite 300, San Diego, CA 92130
GDT maintains a robust intellectual property portfolio supporting the OncoPrecise platform. As of the date of this letter, GDT holds fourteen (14) issued United States patents and seven (7) pending United States patent applications related to the OncoPrecise platform, including claims directed to the TRI scoring algorithm, specific gene panel compositions, and methods of diagnostic use in oncology settings.
GDT has raised approximately $187 million in cumulative funding across its Series A, Series B, and Series C financing rounds. The most recent round, the Series C financing of $78 million, closed on March 28, 2022, and was led by Pinnacle Health Ventures, L.P. These capital resources have supported GDT's ongoing investment in research and development, clinical validation studies, laboratory infrastructure, and commercial operations.
GDT's existing commercial product, OncoPrecise GXP-12, is a 12-gene panel for early-stage breast cancer prognosis. OncoPrecise GXP-12 is currently covered under LCD L38472, which was issued by CFI with an effective date of August 15, 2021. In fiscal year 2023, GDT generated revenue of approximately $6.2 million from OncoPrecise GXP-12 Medicare and commercial payer reimbursement. GDT's successful development, validation, and commercialization of GXP-12 — and its demonstrated track record of productive engagement with the LCD and MolDx review processes — provide a strong foundation for the current request regarding OncoPrecise GXP-47.
III. TEST DESCRIPTION — ONCOPRECISE GXP-47
A. Overview and Intended Clinical Use
OncoPrecise GXP-47 is a laboratory-developed test ("LDT") performed exclusively at GDT's CLIA-certified reference laboratory in San Diego, California. The test utilizes a proprietary 47-gene RNA expression panel to analyze RNA extracted from formalin-fixed, paraffin-embedded ("FFPE") non-small-cell lung cancer ("NSCLC") tumor tissue specimens.
The OncoPrecise GXP-47 assay produces a composite Therapy Response Index ("TRI") score ranging from 0 to 100. The TRI score is calculated using GDT's proprietary algorithm, which integrates the weighted expression values of all 47 genes in the panel to generate a single, clinically actionable index. Based on the TRI score, patients are stratified into three clinically meaningful categories:
• High Likelihood of Response (TRI ≥ 70): Patients in this category are predicted to have a high probability of meaningful clinical benefit from first-line immune checkpoint inhibitor ("ICI") therapy. The TRI score supports the treating oncologist's decision to initiate ICI therapy with confidence.
• Intermediate (TRI 40–69): Patients in this category fall within an intermediate range, in which the predicted probability of ICI response is less certain. The TRI score informs shared decision-making between the oncologist and patient, taking into account the patient's overall clinical profile, comorbidities, preferences, and other relevant factors.
• Low Likelihood of Response (TRI < 40): Patients in this category are predicted to have a low probability of meaningful clinical benefit from first-line ICI therapy. The TRI score supports the treating oncologist's consideration of alternative treatment approaches, including platinum-based chemotherapy or combination regimens, thereby avoiding unnecessary exposure to ICI-related toxicities and costs for patients unlikely to derive therapeutic benefit.
The intended clinical use of OncoPrecise GXP-47 is to guide oncologist decision-making on whether to initiate first-line immune checkpoint inhibitor therapy — including, but not limited to, pembrolizumab (Keytruda), nivolumab (Opdivo), and atezolizumab (Tecentriq) — versus platinum-based chemotherapy in patients with newly diagnosed Stage IIIB or Stage IV NSCLC. The test addresses a recognized and significant unmet clinical need in the management of advanced NSCLC, as existing biomarkers — such as PD-L1 expression by immunohistochemistry and tumor mutational burden ("TMB") — have well-documented limitations in their ability to predict individual patient response to ICI therapy. The proprietary TRI algorithm represents a novel, clinically actionable scoring methodology that is distinct from, and complementary to, these existing biomarkers, and is designed to provide a more comprehensive and accurate prediction of ICI treatment response.
B. Test Methodology
OncoPrecise GXP-47 employs NGS-based RNA expression profiling of 47 carefully selected genes that are associated with immune response pathways, tumor microenvironment characteristics, and checkpoint inhibitor sensitivity. The gene panel was derived through extensive bioinformatics analysis, literature review, and iterative refinement during the development phase of the OncoPrecise platform.
The test is performed on FFPE tumor tissue specimens submitted by ordering clinicians. Upon receipt at GDT's San Diego laboratory, specimens undergo standardized processing for RNA extraction, quality assessment, library preparation, and sequencing on the laboratory's validated NGS instrumentation. The resulting expression data for all 47 genes are processed through GDT's proprietary algorithmic pipeline, which applies gene-specific weighting factors and multivariate modeling to derive the composite TRI score.
All testing is conducted exclusively at GDT's single CLIA-certified, CAP-accredited San Diego laboratory. This single-site testing model ensures the highest standards of quality control, analytical consistency, and standardization across all patient specimens. GDT maintains rigorous internal quality assurance and quality control procedures, including routine proficiency testing, instrument calibration, and process validation, in compliance with all applicable CLIA, CAP, and state clinical laboratory requirements.
C. Patient Population
OncoPrecise GXP-47 is intended for use in patients with newly diagnosed Stage IIIB or Stage IV NSCLC who are candidates for first-line systemic therapy and for whom the choice between ICI monotherapy or ICI-based combination therapy and platinum-based chemotherapy is clinically relevant. This patient population represents a substantial and growing segment of the Medicare beneficiary population, given the rising incidence of NSCLC and the increasing adoption of ICI therapies as standard-of-care first-line treatment options.
The clinical need addressed by OncoPrecise GXP-47 is significant. Although ICI therapies have transformed the treatment landscape for advanced NSCLC, response rates to ICI monotherapy remain modest, typically ranging from 20% to 45% depending on the specific agent, PD-L1 expression level, and patient characteristics. A substantial proportion of patients — often a majority — do not derive meaningful clinical benefit from ICI therapy, yet are exposed to the risks of immune-mediated adverse events and the financial burden of high-cost biologic therapies. Conversely, some patients who might benefit from ICI therapy may be inappropriately directed to chemotherapy based on imprecise or incomplete biomarker information.
By providing a validated, composite genomic index that more accurately predicts ICI response, OncoPrecise GXP-47 addresses this unmet clinical need by enabling more targeted, evidence-informed treatment selection — ultimately improving patient outcomes, reducing unnecessary toxicity, and generating cost savings for the Medicare program.
IV. CODING AND BILLING INFORMATION
GDT has prepared, and intends to submit (or, as applicable, has submitted), a Proprietary Laboratory Analyses ("PLA") code application to the American Medical Association ("AMA") CPT Editorial Panel for OncoPrecise GXP-47. PLA codes are unique, test-specific codes assigned to laboratory-developed tests and are the appropriate coding mechanism for novel molecular diagnostic assays such as OncoPrecise GXP-47.
The proposed PLA code descriptor is as follows:
"OncoPrecise GXP-47 (Genome Dx Therapeutics Inc.), genomic profiling, non-small-cell lung cancer, 47-gene RNA expression panel, formalin-fixed paraffin-embedded tissue, algorithm-derived Therapy Response Index (TRI) score."
Upon assignment by the AMA CPT Editorial Panel, the PLA code will serve as the unique billing code for all Medicare claims submitted by GDT for OncoPrecise GXP-47. GDT anticipates that the PLA code will be assigned in advance of, or concurrent with, any final LCD issued by CFI, and GDT will promptly notify CFI and RAS of the assigned PLA code upon receipt.
Pending PLA code assignment, GDT provides the proposed descriptor and test specifications set forth in this letter and in the accompanying MolDx Technical Assessment Dossier for CFI's and RAS's reference in connection with this LCD request.
GDT has retained Carraway Regulatory Advisors, Inc. to serve as its coding and billing consultant in connection with the OncoPrecise GXP-47 Medicare coverage and reimbursement process. Questions related to coding, billing, or claims submission procedures may be directed to:
Janet Carraway, CPC, CCS-P Principal, Carraway Regulatory Advisors, Inc. 233 South Wacker Drive, Suite 4100 Chicago, IL 60606
Ms. Carraway and her team are available to address any coding-related questions that CFI or RAS may have during the LCD review process.
V. ANALYTICAL VALIDATION
Analytical validation of OncoPrecise GXP-47 was completed on December 14, 2022, at GDT's CLIA-certified, CAP-accredited San Diego reference laboratory. The analytical validation study was designed and conducted in accordance with applicable CLIA regulations (42 C.F.R. Part 493), CAP accreditation standards, and the MolDx program's evidentiary requirements for analytical validity.
The results of the analytical validation study were published in the peer-reviewed journal Journal of Molecular Oncology Diagnostics, Volume 18, Issue 4, pages 412–429, December 2022. A reprint of the published article is enclosed with this submission as Enclosure 3.
The analytical validation study demonstrated the following performance characteristics of OncoPrecise GXP-47:
• Accuracy: The test demonstrated high concordance between measured gene expression values and reference standard values across all 47 genes in the panel, with an overall accuracy rate exceeding established performance benchmarks.
• Precision: Intra-run, inter-run, and inter-operator precision were assessed through replicate testing of standardized reference samples. Coefficients of variation for gene expression measurements and derived TRI scores were within pre-specified acceptance criteria, demonstrating consistent and reproducible performance.
• Reproducibility: Reproducibility was evaluated through testing of identical specimens across multiple runs, operators, and reagent lots. TRI score reproducibility was confirmed, with concordance rates meeting or exceeding pre-specified thresholds.
• Analytical Sensitivity: The test demonstrated the ability to detect and accurately quantify RNA expression levels across the 47-gene panel at clinically relevant thresholds, including specimens with lower RNA input quantities typical of FFPE-derived material.
• Analytical Specificity: The test demonstrated high analytical specificity, with minimal cross-reactivity or interference from non-target RNA species, genomic DNA contamination, or other potential confounders commonly encountered in FFPE-derived specimens.
Full analytical validation data, including detailed study protocols, raw data summaries, and statistical analyses, are included in the accompanying MolDx Technical Assessment Dossier (Section 2). GDT is confident that the analytical validation data for OncoPrecise GXP-47 meet or exceed the evidentiary standards required by the MolDx program for a favorable assessment of analytical validity.
VI. CLINICAL VALIDATION
A. The CLARITY-LUNG Trial
The primary clinical validation evidence supporting OncoPrecise GXP-47 is derived from the CLARITY-LUNG trial, a prospective, multi-site, blinded clinical validation study registered on ClinicalTrials.gov under the identifier NCT05891247.
The CLARITY-LUNG trial was designed to evaluate the clinical validity of the OncoPrecise GXP-47 TRI score as a predictor of response to first-line immune checkpoint inhibitor therapy in patients with newly diagnosed Stage IIIB or Stage IV NSCLC. Key parameters of the trial are summarized below:
• Study Design: Prospective, multi-site, blinded clinical validation study. Treating oncologists and patients were blinded to TRI score results during the treatment decision-making process; TRI scores were determined retrospectively and correlated with clinical outcomes.
• Clinical Sites: The study was conducted across fourteen (14) clinical sites in the United States, including academic medical centers, comprehensive cancer centers, and community oncology practices, ensuring broad geographic and demographic representation of the target patient population.
• Enrollment Timeline and Status: Patient enrollment began on January 18, 2023. The target enrollment for the study is 1,200 patients with newly diagnosed Stage IIIB or Stage IV NSCLC meeting protocol-specified inclusion criteria. As of May 2024, a total of 847 patients have been enrolled, representing approximately 70.58% of the target enrollment.
• Primary Endpoint: The primary endpoint of the CLARITY-LUNG trial is the positive predictive value ("PPV") and negative predictive value ("NPV") of the OncoPrecise GXP-47 TRI score for 12-month progression-free survival ("PFS") on ICI therapy. These endpoints were selected as the most clinically meaningful and statistically rigorous measures of the test's ability to identify patients who will and will not benefit from ICI treatment.
• Pre-Specified Performance Thresholds: The trial protocol pre-specified the following minimum performance thresholds for a determination of clinical validity: PPV ≥ 0.75 and NPV ≥ 0.80. These thresholds were established based on clinical expert consensus, review of the existing biomarker literature, and alignment with MolDx program expectations for clinical validation of molecular diagnostic tests.
• Principal Investigator: Dr. Priya Sundaram, Vice President of Clinical Development, Genome Dx Therapeutics Inc.
• Data Safety Monitoring Board: The CLARITY-LUNG trial is overseen by an independent Data Safety Monitoring Board ("DSMB") chaired by Dr. Evelyn Matsuda, MD, PhD, of the Carrington Cancer Institute, Houston, Texas. The DSMB conducts periodic reviews of safety and efficacy data in accordance with the trial protocol and applicable regulatory requirements.
• Interim Analysis: A pre-planned interim analysis was conducted upon reaching enrollment of 600 patients. The interim analysis data were released on March 29, 2024. The interim results are summarized in the MolDx Technical Assessment Dossier and will be updated with final data results upon completion of the trial. The final data readout is currently projected for the second quarter of 2025, and this section of the LCD request letter will be updated with final results prior to formal submission to CFI.
• Trial Budget: The total budget for the CLARITY-LUNG trial is approximately $28.5 million, reflecting GDT's substantial investment in the generation of rigorous, high-quality clinical validation evidence for OncoPrecise GXP-47.
GDT is committed to providing CFI and RAS with the final CLARITY-LUNG trial results as soon as they are available. GDT believes that the prospective, multi-site, blinded design of the CLARITY-LUNG trial represents a level of clinical validation rigor that is consistent with the highest standards of the MolDx program and provides strong evidentiary support for a positive coverage determination.
B. Supplemental Clinical Evidence
In addition to the CLARITY-LUNG trial, GDT has generated supplemental clinical evidence supporting the clinical validity of OncoPrecise GXP-47 through retrospective studies and sub-group analyses. These supplemental studies are described in detail in the accompanying MolDx Technical Assessment Dossier (Section 3).
GDT has also compiled a comprehensive annotated bibliography of forty-three (43) peer-reviewed publications supporting the evidence base for OncoPrecise GXP-47, including publications addressing the biological rationale for the 47-gene panel composition, the role of immune-related gene expression signatures in predicting ICI response, and the clinical significance of the tumor microenvironment in NSCLC treatment outcomes. The annotated bibliography is included as an appendix to the MolDx Technical Assessment Dossier and as Enclosure 2 to this letter.
VII. CLINICAL UTILITY
OncoPrecise GXP-47 provides actionable, clinically meaningful information that directly impacts treatment decisions in patients with Stage IIIB or Stage IV NSCLC. The clinical utility of the test is grounded in its ability to inform the critical treatment selection decision that oncologists and patients face at the time of first-line therapy initiation: whether to pursue ICI-based therapy or platinum-based chemotherapy.
By identifying patients with a high versus low likelihood of response to ICI therapy, OncoPrecise GXP-47 enables the following clinically meaningful actions:
• Avoidance of costly and potentially toxic ICI therapy in patients unlikely to benefit (TRI < 40): For patients with a low TRI score, the test provides evidence-based support for consideration of alternative therapeutic approaches, such as platinum-based chemotherapy or combination regimens, thereby sparing these patients from the risks of immune-mediated adverse events — including pneumonitis, colitis, hepatitis, and endocrinopathies — that are associated with ICI therapy but unlikely to be offset by therapeutic benefit.
• Confident initiation of ICI therapy in patients with high predicted response (TRI ≥ 70): For patients with a high TRI score, the test reinforces the clinical rationale for ICI-based first-line therapy and provides additional confidence to the treating oncologist and patient that the selected treatment approach is aligned with the patient's genomic profile and predicted response characteristics.
• Informed shared decision-making for intermediate-risk patients (TRI 40–69): For patients falling within the intermediate TRI score range, the test provides valuable contextual information that can be integrated with other clinical factors — including PD-L1 expression, performance status, comorbidity burden, and patient preferences — to support individualized, patient-centered treatment planning. The intermediate category acknowledges the inherent complexity of treatment decision-making in this population and provides a framework for transparent, evidence-informed discussion between the oncologist and patient.
Clinical utility evidence for OncoPrecise GXP-47 is presented in detail in the accompanying MolDx Technical Assessment Dossier (Section 4). This evidence includes data demonstrating that use of TRI scores to guide treatment selection is associated with improved patient outcomes and reduced exposure to ineffective therapies, consistent with the MolDx program's requirement that covered tests provide information that changes clinical management in a manner that benefits patients.
The health economics and outcomes research ("HEOR") analysis supporting the clinical utility and cost-effectiveness of OncoPrecise GXP-47 has been prepared by Larkfield Health Economics, LLC (Dr. Nathan Ostroff, PhD, MS; 7910 Woodmont Avenue, Suite 610, Bethesda, MD 20814) and is included in the MolDx Technical Assessment Dossier (Section 5). The HEOR analysis is further described in Section VIII of this letter.
VIII. HEALTH ECONOMIC ANALYSIS
A comprehensive cost-effectiveness and budget impact analysis for OncoPrecise GXP-47 has been prepared by Larkfield Health Economics, LLC, under the direction of Dr. Nathan Ostroff, PhD, MS. The HEOR analysis is included in the MolDx Technical Assessment Dossier (Section 5).
The HEOR analysis demonstrates that the use of OncoPrecise GXP-47 to guide immune checkpoint inhibitor therapy selection in patients with Stage IIIB or Stage IV NSCLC results in net cost savings to the Medicare program. Specifically, the analysis demonstrates savings attributable to the following mechanisms:
• Reducing inappropriate ICI utilization in predicted non-responders: By identifying patients with a low TRI score (TRI < 40) who are unlikely to benefit from ICI therapy, OncoPrecise GXP-47 supports the avoidance of costly ICI treatment courses in this subgroup. Given the high per-patient cost of ICI therapies — which can exceed $150,000 per year for certain agents and regimens — even modest reductions in inappropriate ICI utilization generate significant cost savings for the Medicare program.
• Decreasing adverse event management costs: Immune-mediated adverse events associated with ICI therapy frequently require costly interventions, including hospitalization, corticosteroid therapy, immunosuppressive agents, and specialist consultations. By reducing the number of patients exposed to ICI therapy who are unlikely to benefit, OncoPrecise GXP-47 is expected to reduce the incidence and associated management costs of these adverse events.
• Improving treatment response rates and progression-free survival outcomes: By directing ICI therapy to the patients most likely to respond (TRI ≥ 70), and facilitating consideration of alternative therapies for patients with low predicted response (TRI < 40), OncoPrecise GXP-47 is expected to improve overall treatment response rates and progression-free survival outcomes within the tested population. Improved outcomes translate to reduced downstream healthcare costs associated with disease progression, second-line and subsequent therapy, and palliative care.
The detailed HEOR analysis, including model assumptions, data sources, sensitivity analyses, and budget impact projections, is set forth in the MolDx Technical Assessment Dossier (Section 5). GDT believes that the health economic evidence further supports a determination that OncoPrecise GXP-47 is medically reasonable and necessary and provides value to the Medicare program and its beneficiaries.
IX. REIMBURSEMENT RATE CONSIDERATIONS
GDT has conducted a crosswalk analysis comparing OncoPrecise GXP-47 to comparable multi-gene, NGS-based oncology diagnostic panels in order to support appropriate Medicare reimbursement rate setting for the test. The crosswalk analysis identified the following primary comparator tests and associated Medicare reimbursement rates:
Based on this crosswalk analysis, GDT respectfully requests that CFI and RAS consider a reimbursement rate of $3,850 per test for OncoPrecise GXP-47. This requested rate represents a premium of approximately 6.28% over the weighted average of the identified crosswalk comparators. GDT believes that this modest premium is justified by several distinguishing characteristics of OncoPrecise GXP-47, including:
• The proprietary Therapy Response Index (TRI) algorithm, which integrates a novel multi-gene scoring methodology not employed by the comparator tests;
• The unique clinical utility of the composite TRI scoring methodology, which provides a single, actionable index score rather than individual gene-level results, simplifying clinical interpretation and decision-making;
• The demonstrated cost savings to the Medicare program associated with the test's ability to guide ICI therapy selection; and
• The substantial investment by GDT in the development, analytical validation, and clinical validation of OncoPrecise GXP-47, including the $28.5 million CLARITY-LUNG trial.
GDT recognizes that final reimbursement rate determination is subject to the applicable crosswalk and/or gapfill pricing process. A detailed crosswalk and gapfill pricing analysis will be provided by GDT during the pricing determination phase of the LCD process, in accordance with applicable procedures.
GDT's Vice President of Market Access & Reimbursement, Kevin Driscoll, is available to provide additional cost, resource utilization, and pricing data as needed to support CFI's and RAS's reimbursement rate analysis. Mr. Driscoll may be contacted at the address set forth in Section XIII of this letter.
X. ACCOMPANYING MOLDX TECHNICAL ASSESSMENT DOSSIER
GDT encloses the MolDx Technical Assessment Dossier for OncoPrecise GXP-47 (Version 1.0) for review by RAS under the MolDx program. The Dossier has been prepared in accordance with the MolDx program's published requirements and guidance for Technical Assessment submissions and contains comprehensive documentation supporting the analytical validity, clinical validity, clinical utility, and health economic value of OncoPrecise GXP-47.
The Dossier is organized into the following sections:
1. Test Description and Intended Use — Detailed description of OncoPrecise GXP-47, including the 47-gene panel composition, testing methodology, intended clinical use, and target patient population.
2. Analytical Validation Data — Complete analytical validation study report, including study design, methods, results, and statistical analyses, demonstrating the accuracy, precision, reproducibility, analytical sensitivity, and analytical specificity of the test.
3. Clinical Validation Data — Clinical validation evidence from the CLARITY-LUNG trial (ClinicalTrials.gov Identifier: NCT05891247), including the trial protocol, interim analysis results, and available clinical outcome data, as well as results from prior retrospective studies and sub-group analyses.
4. Clinical Utility Evidence — Evidence demonstrating that OncoPrecise GXP-47 provides actionable information that changes clinical management in a manner that benefits patients, including data on treatment decision impact and patient outcome improvements.
5. Health Economic Analysis — Cost-effectiveness and budget impact analysis prepared by Larkfield Health Economics, LLC, demonstrating net cost savings to the Medicare program associated with use of OncoPrecise GXP-47 to guide ICI therapy selection.
6. Annotated Bibliography — Annotated bibliography of forty-three (43) peer-reviewed publications supporting the scientific and clinical evidence base for OncoPrecise GXP-47.
GDT respectfully requests that CFI forward the enclosed Dossier to Dr. Catherine Embry, MolDx Technical Assessment Director, at Ridgeline Administrative Services, LLC (1600 Hampton Street, Suite 700, Columbia, SC 29201), for technical assessment review. Alternatively, if CFI advises that direct submission to RAS is appropriate or preferred, GDT will submit the Dossier directly to RAS concurrently with this LCD request submission. GDT is prepared to accommodate whichever submission pathway is consistent with current MolDx program procedures and CFI's preferences.
XI. REGULATORY AND LABORATORY ACCREDITATION INFORMATION
GDT's San Diego reference laboratory is fully certified and accredited under all applicable federal and state clinical laboratory regulatory programs. A summary of GDT's laboratory credentials is provided below:
GDT's laboratory is in full compliance with all applicable federal and state clinical laboratory regulations, including the Clinical Laboratory Improvement Amendments of 1988 ("CLIA"), as amended (42 U.S.C. §§ 263a et seq.), and the implementing regulations at 42 C.F.R. Part 493. The laboratory is also accredited by the College of American Pathologists ("CAP") and participates in all required proficiency testing programs.
OncoPrecise GXP-47 is a laboratory-developed test performed under CLIA regulations at GDT's single, CLIA-certified reference laboratory in San Diego, California. Copies of GDT's current CLIA certificate and CAP accreditation documentation are enclosed with this submission as Enclosure 5.
XII. GDT'S EXISTING MEDICARE COVERAGE HISTORY
GDT has a demonstrated and successful history of engagement with the LCD and MolDx processes. GDT's existing commercial test, OncoPrecise GXP-12 — a 12-gene RNA expression panel for early-stage breast cancer prognosis — has been covered under LCD L38472 since August 15, 2021. LCD L38472 was issued by CFI following a thorough review of GDT's analytical validation, clinical validation, and clinical utility evidence through the MolDx Technical Assessment process.
Since the effective date of LCD L38472, GDT has maintained full compliance with all applicable Medicare coverage requirements and MolDx program standards, including ongoing quality assurance, adverse event reporting, and claims submission procedures. GDT has not been subject to any Medicare coverage denials, recoupments, or compliance actions related to OncoPrecise GXP-12 or any other product.
GDT's prior experience with the LCD process for GXP-12 directly informs and supports the current request for OncoPrecise GXP-47. GDT has applied the lessons learned from the GXP-12 coverage determination — including with respect to the structure and content of the MolDx Technical Assessment Dossier, the design and conduct of clinical validation studies, and the preparation of health economic analyses — to strengthen the evidentiary foundation of the OncoPrecise GXP-47 LCD request.
XIII. CONTACT INFORMATION AND AVAILABILITY
GDT designates the following individuals as contacts for all inquiries related to this LCD request:
Primary Contact — LCD and Reimbursement Inquiries:
Kevin Driscoll Vice President of Market Access & Reimbursement Genome Dx Therapeutics Inc. 4720 Torrey Pines Road, Suite 300 San Diego, CA 92130 Telephone: [___]
Email: [___]
Regulatory and Legal Contact:
Theresa Nakamura General Counsel & Vice President of Regulatory Affairs Genome Dx Therapeutics Inc. 4720 Torrey Pines Road, Suite 300 San Diego, CA 92130 Telephone: [___]
Email: [___]
Outside Counsel:
Miriam Calloway, Esq. Partner, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 1700 K Street NW, Suite 900 Washington, DC 20006 Telephone: [___]
Email: [___]
GDT welcomes the opportunity to participate in any open meeting, Contractor Advisory Committee ("CAC") review, public comment process, or other proceeding related to the proposed LCD for OncoPrecise GXP-47. GDT is prepared to present evidence, respond to questions, and provide supplemental information at any stage of the LCD review process.
XIV. CONCLUSION AND REQUEST
GDT respectfully requests that Cascade Fiscal Intermediaries, LLC take the following actions in response to this submission:
1. Accept this letter and the accompanying MolDx Technical Assessment Dossier (Version 1.0) as a formal request for the initiation of a local coverage determination proceeding for OncoPrecise GXP-47 under the MolDx program;
2. Coordinate with Ridgeline Administrative Services, LLC for the MolDx Technical Assessment review of OncoPrecise GXP-47, including by forwarding the enclosed MolDx Technical Assessment Dossier to Dr. Catherine Embry, MolDx Technical Assessment Director, at RAS, or by advising GDT to submit the Dossier directly to RAS; and
3. Issue a proposed LCD for public comment in due course, with a determination that OncoPrecise GXP-47 is medically reasonable and necessary for use in the identified patient population — specifically, patients with newly diagnosed Stage IIIB or Stage IV NSCLC who are candidates for first-line systemic therapy — and that the test should be covered by the Medicare program under the terms and conditions to be set forth in the LCD.
GDT believes that the clinical evidence, analytical validation data, clinical utility evidence, and health economic data presented in this letter and in the accompanying MolDx Technical Assessment Dossier collectively provide a robust and compelling basis for a positive coverage determination. OncoPrecise GXP-47 represents a meaningful advance in the personalized management of advanced NSCLC, offering the potential to improve patient outcomes, reduce unnecessary treatment-related toxicity, and generate net cost savings for the Medicare program.
GDT is committed to transparency, scientific rigor, and full cooperation throughout the LCD review process. GDT will promptly provide any additional information, data, or documentation that CFI or RAS may require in connection with the evaluation of this request.
We thank Dr. Hargrove, Ms. Phu, and the entire CFI and RAS review teams for their time and consideration of this request, and we look forward to working with CFI and RAS to advance the coverage determination for OncoPrecise GXP-47.
Respectfully submitted,
GENOME DX THERAPEUTICS INC.
By: ________
Name: Anisha Raval, PhD
Title: Co-Founder & Chief Executive Officer
Date: ________
ENCLOSURES
The following enclosures accompany this letter:
Enclosure 1: MolDx Technical Assessment Dossier — OncoPrecise GXP-47 (Version 1.0)
Enclosure 2: Annotated Bibliography (43 peer-reviewed publications)
Enclosure 3: Analytical Validation Publication — Journal of Molecular Oncology Diagnostics, Volume 18, Issue 4, pages 412–429, December 2022
Enclosure 4: CLARITY-LUNG Trial Summary and Protocol Synopsis (ClinicalTrials.gov Identifier: NCT05891247)
Enclosure 5: CLIA Certificate and CAP Accreditation Documentation
Enclosure 6: Proposed PLA Code Application Materials
CC:
Theresa Nakamura, General Counsel & VP of Regulatory Affairs, Genome Dx Therapeutics Inc.
Kevin Driscoll, VP of Market Access & Reimbursement, Genome Dx Therapeutics Inc.
Miriam Calloway, Esq., Partner, Calderwood & Harkness LLP
Dr. Catherine Embry, MolDx Technical Assessment Director, Ridgeline Administrative Services, LLC
Janet Carraway, CPC, CCS-P, Principal, Carraway Regulatory Advisors, Inc.
DRAFT — Prepared by Calderwood & Harkness LLP, Matter No. 1043-00002, Client No. 47832. This letter was not submitted. Matter terminated June 3, 2024. ATTORNEY WORK PRODUCT — PRIVILEGED AND CONFIDENTIAL.
| Code | Test Name (Manufacturer) | Medicare Rate |
| PLA Code 0250U | GeneSight Onco-48 (Elara Genomic Sciences, Inc.) | $3,742 |
| CPT Code 81455 | NGS, solid organ neoplasm, 51 or more genes | $2,919 |
| PLA Code 0239U | TumorMap Pro (Marlowe Asset Management Molecular Diagnostics, Inc.) | $4,206 |
| Weighted Average of Comparators | $3,622.33 | |
| Credential | Detail | |
| CLIA Certificate Number | 05D2187432 | |
| CAP Accreditation Number | 9074821 | |
| National Provider Identifier (NPI) | 1902847365 | |
| Laboratory Address | 4720 Torrey Pines Road, Suite 300, San Diego, CA 92130 |