January 1, 2018 (Vol. 38, No. 1)

Discovery & Development: Evotec Licenses Ncardia’s iPSC Disease-Modeling Technology

Ncardia, a developer of standardized, validated induced pluripotent stem cell (iPSC) assays for disease modeling, has entered into a global nonexclusive licensing agreement with Evotec, a contract research organization. Under the terms of the agreement, Evotec has broad access to intellectual property that Ncardia possesses and may advance target discovery or drug safety and efficacy testing.

In many areas of drug discovery and development, such target discovery and testing activities are constrained because researchers have limited access to patients or tissue samples that correspond to the disease of interest. An alternative approach, one that takes advantage of appropriately reprogrammed stem cells, or patient-derived stem cells, could loosen existing constraints.

“Ncardia’s mission is to support and enable our clients to develop better medicines faster,” commented Stefan Braam, Ph.D., Ncardia’s CEO. “The combination of iPSC-derived disease models with phenotypic screening is an extremely powerful method to identify new drug candidates.”

The use of human iPSCs in disease modeling could also circumvent some of the limitations of animal models. This point was raised recently in Nature Reviews Molecular Cell Biology, in an article that focused on the ability of cultured iPSCs to revolutionize the study of “monogenic, complex, and epigenetic disorders, as well as early- and late-onset diseases.”

The use of iPSCs in drug development and toxicity testing represents just one of the main application-based segments in the larger iPSC market. Other such segments include academic research, regenerative medicine, and cell-based therapeutics. Product function-based market segments include molecular and cellular engineering, cellular reprogramming, cell culture, cell differentiation, and cell analysis.


Genomics & Proteomics: FDA, CMS Approve Foundation Medicine’s Solid Tumor Test with Proposed Coverage

Foundation Medicine has gained FDA approval and a concurrent coverage proposal from the Centers for Medicare & Medicaid Services (CMS) for its FoundationOne CDx™ cancer test, a companion diagnostic designed to detect genetic mutations in 324 genes and two genomic signatures in any solid tumor type.

FoundationOne CDx is a next-generation sequencing (NGS)-based in vitro diagnostic (IVD) device created to detect substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements.

The test is Foundation Medicine’s flagship assay for solid tumor cancers and is indicated as a companion diagnostic for patients with certain types of non-small-cell lung cancer (NSCLC), melanoma, colorectal cancer, ovarian cancer, or breast cancer.

FoundationOne CDx is intended to identify patients who may benefit from treatment with one of 17 on-label targeted therapies, including 12 that are now approved as first-line therapies. The test is also designed to detect genomic signatures, including microsatellite instability (MSI) and tumor mutational burden (TMB), using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens.

FoundationOne CDx results are delivered in an integrated report that identifies alterations matched to FDA-approved therapies, identifies additional alterations in genes known to drive cancer growth, furnishes information about genomic biomarkers (including MSI and TMB), provides clinical trial information, and includes interpretation.

According to the FDA, FoundationOne CDx differs from other companion diagnostics previously approved by the agency, which match one test to one drug.

FoundationOne CDx is the second IVD to be approved and covered following parallel review by the FDA and CMS. The first came in 2014, when the agencies approved and agreed to cover Exact Sciences’ Cologuard®, the first noninvasive DNA screening test for colorectal cancer and the first stool-based diagnostic designed to indicate the presence of red blood cells and DNA mutations that could be lead to cancer.

According to the agencies, parallel review is intended to speed up access to innovative medical technologies for Medicare beneficiaries by allowing test developers to gain approvals plus an immediate proposed Medicare coverage determination from CMS within six months of FDA receipt of a product application.

As a laboratory-developed test, for which the FDA has not enforced premarket review and other requirements, FoundationOne CDx had not been previously submitted for agency review. But at Foundation Medicine’s request, the FDA granted the test its granted Breakthrough Device designation applicable to devices deemed to provide for more effective treatment or diagnosis for life-threatening or irreversibly debilitating diseases for which no approved or cleared treatment exists, or that offer significant advantages over current standard of care.

The FDA established the test’s clinical performance using a “least burdensome” standard in which FoundationOne CDx was compared to previously agency-approved companion diagnostic tests. The test showed approximately 94.6% accuracy in detecting substitutions and short indels representative of the entire 324-gene panel, the FDA said. The agency divided its assessment of FoundationOne CDx into a clinical review conducted by the Center for Devices and Radiological Health (CDRH), with support from the agency’s Oncology Center of Excellence, and a review of all other aspects of the test, followed by a final approval determination by the CDRH. Concurrent with FDA approval, CMS has issued a preliminary National Coverage Determination (NCD) for FoundationOne CDx and other similar NGS IVDs for Medicare beneficiaries with advanced cancer—including recurrent, metastatic, or advanced Stage IV cancer—who have not been previously tested using the same NGS technology and continue to seek further cancer therapy. The draft NCD would provide coverage for FDA-approved companion diagnostic claims, as well as a pathway for additional coverage with evidence of development in other solid tumor types, Foundation Medicine said. The final policy is expected to issue during the first quarter of 2018 following periods of public comment and administrative review. Upon finalization of the NCD, FoundationOne CDx is expected to be commercially available, Foundation Medicine said.  


Molecular Diagnostics: Janssen to Use Genomic Health’s Test in Prostate Cancer Collab

Genomic Health announced recently that its Oncotype DX Genomic Prostate Score (GPS) test will be evaluated for the prostate cancer drug pipeline of Johnson & Johnson’s Janssen Pharmaceuticals through a research collaboration whose value was not disclosed.

Under the terms of the deal, Genomic Health has agreed to test samples from Janssen studies, while the drug developer agreed to the use of GPS for the evaluation, with the goal of examining the association between GPS results with clinical outcomes.

“Janssen is a recognized leader in oncology, and their selection of the Oncotype DX GPS test reflects the best-in-class value that it delivers in stratifying patient risk, and may reveal potential for guiding treatment selection for prostate cancer patients in the future,” Phil Febbo, M.D., Genomic Health’s CMO, said in a statement.

Oncotype DX GPS is designed to help professionals assess clinical risk and tumor aggressiveness, to decide whether immediate treatment is necessary, or opt instead for active surveillance. According to Genomic Health, the GPS assay is the only genomic assay designed for men with clinically low-risk cancer to help make treatment decisions at the time of diagnosis.

GPS is designed to examine interactions among genes in the tumor in clinically low-risk prostate cancer patients (GS 3+3 and 3+4). The test, based on multiple studies with Cleveland Clinic, provides a result ranging from 0–100 that corresponds to the biologic aggressiveness of the tumor, and measures biology through the expression of 17 genes across four important genetic pathways and—in conjunction with clinical risk factors—predicts the likelihood of adverse pathology.





























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