Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 1 of 15 PageID #: 10146
`
`IN THE UNITED STATES DISTRICT COURT
`FOR THE DISTRICT OF DELAWARE
`
`GUARDANT HEALTH, INC.,
`Plaintiff,
`
`v.
`FOUNDATION MEDICINE, INC.,
`Defendant.
`
`
`
`
`C. A. No. 20-cv-01580-LPS
`
`
`
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`
`
`DECLARATION OF ELIZABETH MANSFIELD, PH.D.
`
`I, Elizabeth Mansfield, Ph.D., hereby declare as follows:
`
`I.
`
`QUALIFICATIONS
`
`1.
`
`I am currently the Vice President of Regulatory Affairs at Foundation Medicine,
`
`Inc. (“FMI”). I have been employed by FMI in this position since July 2020.
`
`2.
`
`I understand that Guardant Health, Inc. (“Guardant”) has filed a motion for a
`
`preliminary injunction seeking to preclude FMI from continuing to use or sell its FDA-approved
`
`FoundationOne® Liquid CDx test. I make this Declaration in support of FMI’s opposition to that
`
`motion.
`
`3.
`
`FMI develops and sells a suite of comprehensive genomic profiling (“CGP”) tests
`
`and companion diagnostics that are used by physicians and FMI’s biotech and pharmaceutical
`
`company customers to identify molecular alterations in blood or tissue samples taken from cancer
`
`patients in order to match patients with relevant targeted therapies, immunotherapies, and clinical
`
`trials based on the patient’s individual genomic profile.
`
`4.
`
`I am responsible for FMI’s efforts to obtain and maintain government approval for
`
`its CGP tests and companion diagnostics. My duties and responsibilities include, among other
`
`Public Version Filed: March 5, 2021
`
`Confidential Version Filed: February 26, 2021
`
`PUBLIC VERSION
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 2 of 15 PageID #: 10147
`
`things, overseeing FMI’s submissions to, and correspondence with, the United States Food and
`
`Drug Administration (“FDA”) (collectively, “FDA Communications”). As a result of my role at
`
`FMI, I have personal knowledge of, and am familiar with, FMI’s FDA Communications relating
`
`to FoundationOne® Liquid CDx and the gene mutations and therapies for which its use has been
`
`approved by FDA. Due to my years of experience working with and at FDA, I also am familiar
`
`with communication standards between FDA and industry sponsors such as FMI.
`
`5.
`
`I received a Bachelor’s Degree in Biology from the University of Pennsylvania in
`
`1986. I received a Ph.D. in Biochemistry from Johns Hopkins University in 1993. I completed
`
`further postdoctoral training at the National Cancer Institute in 1993 through 1996 and the National
`
`Institute for Arthritis, Musculoskeletal, and Skin Diseases in 1996 through 2001.
`
`6.
`
`Before taking my current position at FMI, from February 2017 until June 2019, I
`
`was the Head/VP of Regulatory Strategy at GRAIL, Inc. (“GRAIL”), a healthcare company
`
`established to develop an early cancer genetic screening test designed to detect early stage cancer
`
`at a time before the patient has experienced symptoms. From July 2019 until July 2020, I was a
`
`consultant to GRAIL on regulatory matters.
`
`7.
`
`From 2006 until February 2017, I worked for FDA. I held several positions during
`
`my tenure at the agency. In my most recent position, I was the Director of the Personalized
`
`Medicine Staff in the Office of In Vitro Diagnostic Device (“OIVD”, later called the Office of In
`
`Vitro Diagnostics and Radiological Health, or “OIR”), in the Center for Devices and Radiological
`
`Health, where I developed a program to address companion and novel diagnostic devices. In this
`
`role, I was involved in developing and setting the definition for, and writing the FDA Guidance
`
`Document for, companion diagnostic (“CDx”) devices and developing and setting guidelines for
`
`the request for, and granting of, CDx status by FDA. I was also involved at the Center, Agency,
`
`
`
`2
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 3 of 15 PageID #: 10148
`
`and Department level in developing a strategy and policy to modify FDA’s historical practice of
`
`enforcement discretion for laboratory developed tests. I was previously a Senior Policy Analyst
`
`in the Office of In Vitro Diagnostic Devices where I managed a variety of policy and scientific
`
`issues. From 2001-2004, I also previously served in other positions at FDA, such as Scientific
`
`Reviewer and Genetics Expert.
`
`8.
`
`From 2004 to 2006, I served as the Director of Regulatory Affairs at Affymetrix,
`
`Inc.
`
`9.
`
`As a result of my employment experience, I am very familiar with the process and
`
`procedures that companies like FMI must follow in order to obtain FDA approval of their
`
`diagnostic tests.
`
`II.
`
`FMI’s Comprehensive Genomic Profiling Tests
`
`10.
`
`FMI’s current commercial testing portfolio includes two FDA approved tests:
`
`FoundationOne® CDx and FoundationOne® Liquid CDx.
`
`11.
`
`FoundationOne® CDx is the first FDA-approved tissue-based comprehensive
`
`genomic profiling companion diagnostic for solid tumors, now indicated for over 20 targeted
`
`therapies. FoundationOne® CDx was the first solid tumor CGP test approved by FDA and the
`
`Centers for Medicare and Medicaid Services (“CMS”) in their Parallel Review program. Initial
`
`FDA approval was based on analytic validation and non-inferiority concordance studies
`
`with FDA-approved assays. It was first approved by FDA in November 2017 – nearly three years
`
`before FDA approved the FMI and Guardant blood-based CGP tests described below. FMI has
`
`subsequently gained FDA approval for a number of additional companion diagnostic claims, based
`
`on analytical validity and clinical bridging or direct efficacy analysis with the therapeutic trial
`
`outcome.
`
`
`
`3
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 4 of 15 PageID #: 10149
`
`12.
`
`As discussed in more detail below, FoundationOne® Liquid CDx is intended to
`
`provide tumor mutation profiling in oncology for patients with solid malignant neoplasms.
`
`FoundationOne® Liquid CDx is an FDA-approved companion diagnostic currently indicated for
`
`seven targeted therapies across four different cancer types. See Ex. 5 at 2.1
`
`III.
`
`FDA’s Approval of FoundationOne® Liquid CDx
`
`13.
`
`FDA approved FoundationOne® Liquid CDx in August 2020. It is a successor test
`
`of FoundationOne® Liquid, which launched in 2018. FoundationOne® Liquid was essentially a
`
`rebranding of FMI’s original FoundationACT® liquid biopsy, which launched in 2016.
`
`FoundationOne® Liquid CDx uses plasma from peripheral blood as the sample type, and analyzes
`
`cell-free DNA (cfDNA) extracted from the plasma.
`
`14.
`
`On March 30, 2018, FMI submitted to FDA a Breakthrough Device Request for the
`
`test that would eventually be called FoundationOne® Liquid CDx, but was at that time named
`
`FoundationACT® CDx. Ex. 18, at 608.
`
`15.
`
`FMI’s Breakthrough Device application stated that: “There are currently no
`
`approved or cleared blood-based in vitro diagnostics genomic profiling assays using cfDNA
`
`extracted from blood targeting multiple genes, alteration types and genomic signature across
`
`several cancer indications. Because no FDA-approved alternatives currently exist, the FACT CDx
`
`test would fulfill a significant unmet medical need for advanced cancer patients that do not have a
`
`tissue sample available for testing.” Id. at 614.
`
`
`1 All exhibits referred to herein are attached to the Appendix in Support of FMI’s Brief in
`Opposition to Guardant’s Motion for Preliminary Injunction.
`4
`
`
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 5 of 15 PageID #: 10150
`
`16.
`
`FDA granted FMI’s request for Breakthrough Device Designation on April 25,
`
`2018. See Ex. 19, at 618. FMI publicly announced the FDA’s Breakthrough Designation in a
`
`press release issued on April 26, 2018. Ex. 20.
`
`17.
`
`Breakthrough Device Designation allows a device manufacturer to have a
`
`prioritized review of its premarket approval application, among other benefits. FDA will grant
`
`Breakthrough Device Designation after it determines that the device provides for more effective
`
`treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions;
`
`and it meets at least one of the following criteria: (A) represents breakthrough technologies; (B)
`
`for which no approved or cleared alternatives exist; (C) that offers significant advantages over
`
`existing approved or cleared alternatives, including the potential, compared to existing approved
`
`alternatives, to reduce or eliminate the need for hospitalization, improve patient quality of life,
`
`facilitate patients’ ability to manage their own care (such as through self-directed personal
`
`assistance), or establishes long-term clinical efficiencies; or (D) the availability of which is in the
`
`best interest of patients. See 21 U.S. Code § 360e-3(b).
`
`18.
`
`On December 20, 2018, FMI submitted its Premarket Approval (“PMA”) Module
`
`1. Ex. 22, at 093; Ex. 23. This module was submitted under the Modular PMA review program
`
`provided by FDA for the purpose initiating a Modular PMA review of FoundationOne® Liquid
`
`CDx, in order to obtain FDA approval for the product through the Class III premarket approval
`
`process.
`
`19.
`
`FMI submitted additional modules and an additional PMA filing to demonstrate
`
`and validate that FoundationOne® Liquid CDx was safe and effective for its intended uses,
`
`culminating in a determination from FDA that its PMA for FoundationOne® Liquid CDx was
`
`“approvable” on July 20, 2020, and approval for commercial use for CDx indications on August
`
`
`
`5
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 6 of 15 PageID #: 10151
`
`26, 2020, October 26, 2020, and November 6, 2020. Ex. 24, Ex. 136, Ex. 129, Ex. 138; see also
`
`Ex. 25, Ex. 137, Ex. 7.
`
`20.
`
`I understand from a Guardant press release that Breakthrough Designation for
`
`Guardant360® was announced on February 15, 2018. Ex. 17. Thus, it appears that both FMI and
`
`Guardant proceeded in parallel with respect to seeking approval of their liquid biopsies as FDA-
`
`approved companion diagnostics.
`
`21.
`
`FMI devoted substantial time and invested tens of millions of dollars in research
`
`and development related to FoundationOne® Liquid CDx, including, for example, approximately
`
`$30 million alone for the validation and regulatory approval of FoundationOne® Liquid CDx.
`
`IV. Regulatory Significance of CDx Designation
`A companion diagnostic, or “CDx”, is a medical device that provides information
`22.
`
`that is essential for the safe and effective use of a corresponding therapeutic product. One use of
`
`a CDx is to identify patients who are most likely to benefit from a particular therapeutic treatment.
`
`The precision and accuracy of this identification is critical in order to give physicians the best and
`
`most complete information possible in making treatment recommendations for patients. If the
`
`diagnostic test is not accurate, it could result in the choice of an ineffective or less effective
`
`treatment option for the cancer patient.
`
`23.
`
`FDA approval denotes that the test has been deemed safe and effective for its
`
`intended use by an independent regulatory body charged with the mission of ensuring that
`
`diagnostic tests and associated treatments are safe and effective for patients. In my experience,
`
`when given the option, many practitioners prefer to utilize FDA-approved CDx tests, as opposed
`
`to an LDT test that has not been reviewed and approved by FDA.
`
`
`
`6
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 7 of 15 PageID #: 10152
`
`24. Most laboratory developed tests (“LDTs”) have not been approved by FDA, and
`
`unless approved by FDA, cannot make CDx claims. An LDT is an in vitro diagnostic test that is
`
`designed, manufactured, and used within a single laboratory. This type of test often is brought to
`
`market under FDA’s exercise of enforcement discretion (i.e., without FDA review) and has
`
`performance characteristics that are often known only to the manufacturer. Importantly, unless
`
`submitted to FDA for review, FDA has not independently verified that these tests can be used to
`
`identify an appropriate patient population for a therapeutic product. LDTs not reviewed by FDA
`
`may not be supported by the robust quality systems required by FDA in order to find a device
`
`approvable. Quality systems ensure that tests are designed and manufactured in a manner that
`
`ensures validity and quality over time.
`
`25.
`
`Guardant360® LDT is not an FDA approved CDx, as noted in the Declaration of
`
`Daniel Simon, who I understand is Guardant’s Senior Vice President of Biopharmaceutical
`
`Business Development. A non-CDx LDT does not have to go through a rigorous approval process
`
`and, therefore, may have different performance in predicting appropriate patients for a given
`
`therapy. In order to establish that a CDx can select the correct patients for drug therapies, the test
`
`manufacturer must either demonstrate through testing of drug clinical trial samples, or through a
`
`non-inferiority test, that the test would correctly predict which patients could benefit from the
`
`therapies.
`
`26.
`
`FDA has expressed several concerns with the use of LDTs. For example, it has
`
`stated: “LDT’s are important to the continued development of personalized medicine, so it is
`
`important that in vitro diagnostics are accurate so that patients and health care providers do not
`
`seek unnecessary treatments, delay needed treatments, or become exposed to inappropriate
`
`therapies … The FDA has identified problems with several high-risk LDTs including: claims that
`
`
`
`7
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 8 of 15 PageID #: 10153
`
`are not adequately supported with evidence; lack of appropriate controls yielding erroneous
`
`results; and falsification of data. The FDA is concerned that people could initiate unnecessary
`
`treatment or delay or forego treatment altogether for a health condition, which could result in
`
`illness or death. The FDA is aware of faulty LDTs that could have led to …cancer patients being
`
`exposed to inappropriate therapies or not getting effective therapies.” Ex. 21, Laboratory
`
`Developed Tests, FDA,
`
`(Sept. 27, 2018), https://www.fda.gov/medical-devices/vitro-
`
`diagnostics/laboratory-developed-tests.
`
`V.
`
`Key Differences Between Guardant360® CDx and FoundationOne® Liquid CDx
`
`A.
`27.
`
`FoundationOne® Liquid CDx
`
`FoundationOne® Liquid CDx is a qualitative next-generation sequencing based in
`
`vitro diagnostic using cfDNA extracted from plasma that has been approved by FDA to detect and
`
`report the presence of genetic alterations in 311 genes. Ex. 5, at 2, 4; see also Ex. 4. The test has
`
`been reviewed and approved by FDA to be used as a companion diagnostic to identify patients
`
`who may benefit from treatment with the targeted therapies listed in the following table in
`
`accordance with approved therapeutic product labeling:
`
`Tumor Type
`
`Biomarker(s) Detected
`
`Therapy
`
`ALK rearrangements
`
`ALECENSA® (alectinib)
`
`Non-small cell lung
`cancer (“NSCLC”)
`
`EGFR Exon 19 deletions and
`
`EGFR Exon 21 L858R substitution
`
`IRESSA® (gefitinib)
`
`TAGRISSO® (osimertinib)
`
`TARCEVA® (erlotinib)
`
`Prostate cancer
`
`BRCA1, BRCA2, ATM alterations LYNPARZA® (olaparib)
`
`BRCA1, BRCA2 alterations
`
`RUBRACA® (rucaparib)
`
`Ovarian cancer
`
`BRCA1, BRCA2 alterations
`
`RUBRACA® (rucaparib)
`
`
`
`8
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 9 of 15 PageID #: 10154
`
`Breast cancer
`
`PIK3CA mutations C420R, E542K,
`E545A, E545D [1635G>T only],
`E545G, E545K, Q546E, Q546R;
`and H1047L, H1047R, and
`H1047Y
`
`PIQRAY® (alpelisib)
`
`
`
`Ex. 5, at 2.
`
`28.
`
`As indicated in this Table, FoundationOne® Liquid CDx is approved as a CDx for
`
`seven therapies that target four different tumor types: NSCLC; prostate cancer; ovarian cancer;
`
`and breast cancer.
`
`29.
`
` Alecensa® (alectinib) is indicated for the treatment of patients with anaplastic
`
`lymphoma kinase (ALK)-positive metastatic NSCLC as detected by an FDA-approved test. Ex.
`
`11.
`
`30.
`
`Iressa® (gefitinib) is a tyrosine kinase inhibitor indicted for the first-line treatment
`
`of patients with metastatic NSCLC whose tumors have epidermal growth factor receptor
`
`(“EGFR”) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-
`
`approved test. Ex. 12.
`
`31.
`
`Tagrisso® (osimertinib) is a kinase inhibitor indicated for adjuvant therapy after
`
`tumor resection in adult patients with NSCLC whose tumors have EGFR exon 19 deletions or exon
`
`21 (L858R) mutations, as detected by an FDA-approved test; as the first-line treatment of adult
`
`patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R)
`
`mutations, as detected by an FDA-approved test; or the treatment of adult patients with metastatic
`
`EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease
`
`has progressed on or after EGFR TKI therapy. Ex. 14.
`
`
`
`9
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 10 of 15 PageID #: 10155
`
`32.
`
`Tarceva® (erlotinib) is indicated for the treatment of patients with metastatic
`
`NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations
`
`as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line
`
`treatment after progression following at least one prior chemotherapy regimen. Ex. 10.
`
`33.
`
`Lynparza® (olaparib) is indicated for treatment of adult patients with deleterious
`
`or suspected deleterious germline or somatic homologous recombination repair (“HRR”) gene-
`
`mutated metastatic castration-resistant prostate cancer (“mCRPC”) who have progressed
`
`following prior treatment with enzalutamide or abiraterone. Ex. 8. Selection of patients is based
`
`on the presence of deleterious or suspected deleterious HRR gene mutations in tissue or blood
`
`samples, including (in tissue) ATMm , BRCA1m, BRCA2m, BARD1m, BRIP1m, CDK12m,
`
`CHEK1m, CHEK2m, FANCLm, PALB2m, RAD51Bm, RAD51Cm, RAD51Dm, and
`
`RAD54Lm; and (in blood), gBRCA1m and gBRCA2m. Id. at Table 1. The FDA label for
`
`Lynparza® states that in order to determine the presence of these mutations, selection should be
`
`done based on an FDA-approved CDx for olaparib. See Ex. 8.
`
`34.
`
`Rubraca® (rucaparib) is indicated for the treatment of adult patients with a
`
`deleterious BRCA mutation (germline and/or somatic)-associated epithelial ovarian, fallopian
`
`tube, or primary peritoneal cancer who have been treated with two or more chemotherapies. Ex.
`
`3. Rubraca® (rucaparib) is also indicated for the treatment of adult patients with a deleterious
`
`BRCA mutation (germline and/or somatic)-associated mCRPC who have been treated with
`
`androgen receptor-directed therapy and a taxane-based chemotherapy. Id. The FDA label for
`
`Rubraca® states that in order to determine the presence of these mutations, selection should be
`
`done based on an FDA-approved CDx for rucaparib. Id.
`
`
`
`10
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 11 of 15 PageID #: 10156
`
`35.
`
`Piqray® (alpelisib) is a kinase inhibitor indicated in combination with fulvestrant
`
`for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive,
`
`human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or
`
`metastatic breast cancer as detected by an FDA-approved test following progression on or after an
`
`endocrine-based regimen. Ex. 13.
`
`36.
`
`For each of the above listed therapies – with the exception of Tagrisso® –
`
`FoundationOne® Liquid CDx is the only comprehensive genomic profiling liquid test that has
`
`been approved by FDA to be used as a CDx to identify patients who may benefit from treatment
`
`with those targeted therapies.2 See Ex. 9, at 12-13.
`
`37.
`
`The intended use of each of the CDx indications in the FoundationOne® Liquid
`
`CDx was supported by a clinical validity study (with the exception of the EGFR CDx indications,
`
`which were supported by a non-inferiority study which demonstrated that FoundationOne® Liquid
`
`CDx performs at least as good as (is not inferior to) the original non-CGP Roche CDx liquid biopsy
`
`assay). See Ex. 5 at 34-43 and Table 4. This means that FDA has found that FoundationOne®
`
`Liquid CDx is both safe and effective to detect mutations in 311 genes and to identify patients who
`
`may benefit from the targeted therapies identified in the Table above.
`
`38.
`
` In addition to the FDA approvals identified above, in collaboration with its partner,
`
`Novartis Pharmaceutical Corporation, FMI is seeking to expand the intended use (IU) of
`
`FoundationOne® Liquid CDx to identify NSCLC patients with certain qualifying MET exon 14
`
`alterations who are eligible for treatment with capmatinib. Capmatinib is a kinase inhibitor
`
`
`2 There are two liquid FDA-approved CDx tests, which only test for the presence of alterations in
`one or a few specific mutations. These tests are not comprehensive genomic profiling tests and,
`therefore, will only provide information about a specific mutation tested for, as opposed to
`providing information about all potential genetic mutations.
`11
`
`
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 12 of 15 PageID #: 10157
`
`approved by the FDA as a treatment for NSCLC patients whose tumors have particular MET exon
`
`14 mutations. The mutation must be detected by an FDA approved test. Capmatinib is sold by
`
`Novartis under the tradename Tabrecta®.
`
`39.
`
`The greater number of genomic mutations that are identified by FMI’s tests gives
`
`practitioners and patients additional knowledge about patient prognosis and clinical trial options.
`
`FoundationOne® Liquid CDx is FDA approved to test for mutations in 256 more genes relevant
`
`to cancer than Guardant360® CDx (FoundationOne® Liquid CDx tests for mutations in 311 genes
`
`while Guardant360® CDx tests for mutations in 55 genes). There are several genes that Guardant
`
`does not test for in any of its assays, but FoundationOne® Liquid CDx does test for, which have
`
`significant known clinical outcomes. For example, high CUL4A expression has been associated
`
`with inferior survival in patients with breast cancer, and CYP17A1 amplification has been
`
`associated with worse prognosis in patients with castrate-resistant prostate cancer (“CRPC”)
`
`treated with the CYP17A1 inhibitor abiraterone. See Ex. 15; Ex. 16.
`
`B.
`40.
`
`Guardant360® CDx
`
`In comparison to FoundationOne® Liquid CDx, which is approved by FDA to
`
`detect mutations in 311 genes, and as a CDx for seven therapies targeting four tumor types, it is
`
`my understanding, based on publicly-available information, that Guardant360® CDx has been
`
`approved by FDA to detect mutations in 55 genes, and has been approved as a CDx for only one
`
`tumor type (NSCLC) and only one therapy (Tagrisso® (osimertinib)). See Ex. 2, at 1.
`
`41.
`
`The difference between the seven therapies that FoundationOne® Liquid CDx is
`
`approved for and the one that Guardant360® CDx is approved for is apparent on the FDA’s
`
`published List of Cleared or Approved Companion Diagnostic Devices. See Ex. 9, at 12-13.
`
`
`
`12
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 13 of 15 PageID #: 10158
`
`42.
`
`FoundationOne® Liquid CDx also tests for a subset of targeted regions in 75 genes
`
`with enhanced sensitivity. See Ex. 5, at 4. This means that FMI can detect mutations in these
`
`regions when present at lower allelic frequency. Within these 75 genes there are 18 mutations
`
`(ABL1, ATR, BTK, CD274, CHEK2, CRKL, ERBB3, ERRFI1, ETV6, FLT3, FOXL2, MDM2 ,
`
`MYCN, MYD88, PALB2, PDCD1LG2, PDGFRB, VEGFA) that Guardant360® CDx does not
`
`even test, and another ten genes that Guardant includes but does not report in Guardant360® CDx.
`
`See Ex. 26.
`
`VI.
`
`The Detrimental Impact of Removing FoundationOne® Liquid CDx from the Market
`
`43.
`
`I understand that Guardant is seeking an order that would prevent FMI from using
`
`or selling FoundationOne® Liquid CDx.
`
`44.
`
`FoundationOne® Liquid CDx is the only CGP liquid test that has been approved
`
`by FDA as a CDx to identify patients who may benefit from treatment with six out of the seven
`
`targeted therapies identified in the Table above. Patients who could benefit from these six
`
`therapies will no longer have the benefit of a liquid CGP assay that has been determined to be safe
`
`and effective by FDA for the identification of eligibility for these six therapies.
`
`45.
`
`Its removal from the market would also have a significant impact on clinicians who
`
`order FoundationOne® Liquid CDx and rely on its results to develop personalized treatment plans
`
`for their cancer patients. Clinicians utilize a CDx in assessing what the treatment or treatment
`
`strategy should be, which improves patient outcomes, and prevents patients from being exposed
`
`to unnecessary therapies and their associated toxicities.
`
`46.
`
`Its removal from the market would also have a significant impact on FMI’s
`
`biopharma partners who have used and continue to use the test to develop and obtain approval for
`
`new therapeutic treatments.
`
`
`
`
`
`13
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 14 of 15 PageID #: 10159
`
`
`
`.
`
`47.
`
`FMI will often work collaboratively with a biopharma company to develop a
`
`therapy and an associated companion diagnostic that is effective for a specific population of
`
`patients. The biopharma company will use FMI’s comprehensive genomic profiling tests to
`
`identify the patient population best suited for clinical trials and the therapy it is developing.
`
`Identification of a specific patient population who is more likely to benefit makes it more likely
`
`that a trial can be successful and thus improves the likelihood of a positive outcome for the patient.
`
`48.
`
`Furthermore, if FDA has determined that a CDx is needed for a drug’s safe and
`
`effective use, then the drug generally cannot be approved without the approval of the CDx
`
`(although there are exceptions for therapies that are eligible for accelerated approval where CDx
`
`approval is still required but may temporally follow drug approval, i.e., in the post-market setting).
`
`49.
`
`FMI collaborated with biopharma companies Novartis, Clovis, AstraZeneca, and
`
`Genentech in obtaining FDA approval for FoundationOne® Liquid CDx and the drug therapies
`
`indicated by the CDx. This process included demonstrating technical performance met desired
`
`thresholds, providing clinical trial samples to assess clinical performance of the test, and sharing
`
`information from clinical studies. This process requires a significant investment by both parties.
`
`
`
`
`
`
`
`
`
`
`
`14
`
`

`

`Case 1:20-cv-01580-LPS Document 45 Filed 03/05/21 Page 15 of 15 PageID #: 10160
`
`I declare under penalty of perjury under the laws of the United States that the foregoing
`
`and the content of my Declaration are true and correct to the best of my knowledge. Executed this
`
`26th day of February 2021, in Kensington, Maryland.
`
`______________________
`Elizabeth Mansfield, PhD.
`
`
`
`
`
`
`
`
`
`
`
`15
`
`