LCD announces coverage for PGx testing under Medicare

The Centers for Medicare and Medicaid Services (CMS) have posted a FUTURE Local Coverage Determination (LCD) for MolDX: Pharmacogenomics Testing (L38294). This includes broad coverage for pharmacogenomic testing to go in effect this summer.

CPIC provided presentations to Palmetto prior to their draft LCD, and provided written comments on LCD ID L38294 back in November of 2019. CPIC members were instrumental in the feedback provided, and many of CPIC’s suggestions have been incorporated, and CPIC guidelines are cited throughout their document. For example, their post states:  “PGx tests are indicated when medications are being considered for use (or already being administered) that are medically necessary, appropriate, and approved for use in the patient’s condition and are known to have a gene(s)-drug interaction that has been demonstrated to be clinically actionable as defined by the FDA (PGx information required for safe drug administration) or Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines (category A and B).”

The LCD defines ‘actionable use’ of PGx as “when the genotype information may lead to selection of or avoidance of a specific therapy or modification of dosage of a therapy. The selection, avoidance, or dose change must be based on the FDA-label for the drug, an FDA warning or safety concern, or a CPIC level A or B gene-drug interaction”. PharmGKB uses the ‘Alternate Drug’ and ‘Dosing Info’ tags to highlight drug label annotations where the label contains information about contraindications or dosing changes based on genotype information. These tags can be used to filter our table of drug label annotations.

PGRN Transition

After 20 years of NIH funding, the Pharmacogenomics Research Network (PGRN) is becoming an independent scientific society on July 1, 2020. The deadline for becoming a founding member has been extended. If you are interested in joining, please visit www.pgrn.org.

On behalf of all of the NIH PGRN funded investigators, we thank NIH for their past support, particularly our original program officer, Dr. Rochelle Long (NIGMS Director, Division of Pharmacology, Physiology and Biological Chemistry).

Update 6/29/2020 The inaugural Research In Progress (RIPS) webinar from the PGRN society will be given by Alan Shuldiner, MD, on Friday July 17 at 11am Eastern time. Dr. Shuldiner will speak on "Building bridges between industry, academia, health care systems and communities to advance Precision Medicine".

From Friday August 14, RIPS webinars will be held on the second Friday of every month at 11am Eastern time for all PGRN members. A schedule of upcoming RIPS webinars can be found here. If you are interested in joining the PGRN, you can become a member at www.pgrn.org.

Dr. Stuart Scott joins Stanford

We are pleased to announce that Dr. Stuart Scott will be joining Stanford University as a Professor in the Department of Pathology effective 1 September 2020. In addition, Dr. Scott will be Laboratory Director of the Stanford Medicine Clinical Genomics Program. Dr. Scott is moving from the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and Sema4 (previously the Mount Sinai Genetic Testing Laboratory). He is certified by the American Board of Medical Genetics and Genomics in both Clinical Molecular Genetics and Clinical Cytogenetics and Genomics. Dr. Scott’s research interests include pharmacogenomics (PGx), cytogenomics, epigenomics, and the implementation of genomic medicine. He has long standing collaborations with Stanford’s multi-institutional efforts in PGx including PharmGKB, CPIC, PharmVar and PharmCAT.

DPYD goes live on PharmVar

PharmVar has announced the introduction of DPYD to its database. DYPD is the rate limiting enzyme involved in the catabolism of fluoropyrimidines (5-fluorouracil and capecitabine) which are used in several cancer treatment regimens. Clinical laboratories provide preemptive DPYD genotyping to avoid potentially life-threatening toxicity in patients carrying DPYD risk alleles. Annotations of clinical guidelines for DPYD are available on PharmGKB here.

Prior to its introduction to PharmVar, there was no centralized resource for DPYD nomenclature. Some of the allelic variants were assigned star allele numbers when first published (DPYD*1-*13) or were referred to by a trivial name.

Although star nomenclature based on haplotypes was initially used to name DPYD variants, this system was deemed impractical for DPYD due to the size of the gene and recombination between exons. To accommodate DPYD (and other genes with similar challenges in the future), PharmVar has developed a gene page format using rsIDs as PharmVar names instead of star allele designations.

Check out the new DPYD page at https://www.pharmvar.org/gene/DPYD. PharmVar welcomes any feedback and encourages DPYD submissions to grow its inventory.

PharmGKB response to the FDA Table for Pharmacogenetic Associations

In February, the FDA posted the Table for Pharmacogenetic Associations (PGx Table), and PharmGKB and CPIC blogged about the table a few days later.  We identified substantial areas of overlap and some differences between the gene-drug pairs listed on the FDA table and those with published CPIC guidelines. It is important to note that the FDA PGx Table, CPIC, and PharmGKB may update their content at any time. These comments reflect the PGx table as of May 2020,

As of the current posting, the evidence the FDA used to construct the PGx Table is not explicitly posted, although most of the gene-drug pairs with therapeutic management recommendations on the PGx Table have labels also listed on FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling (Biomarker Table) containing some kind of prescribing information as defined by PharmGKB. The CPIC process for creating guidelines has been published and involves field experts conducting extensive reviews of the peer-reviewed literature, all of which is cited or listed as supporting evidence in the guideline publications.

Direct comparison of which gene-drug pairs have CPIC guidelines versus which are listed on the FDA PGx Table is difficult due to the completely different manners in which the pairs are selected and ranked, as well as the different content and purposes of CPIC and the FDA PGx Table. 

Here we present our compilation tables of the gene-drug pairs on FDA’s PGx table with CPIC gene-drug pairs (some of which have guidelines, some are pending, and some are not considered actionable), PharmGKB annotations of drug labels found on FDA’s Biomarker Table, PharmGKB clinical annotations, and PharmGKB annotations of clinical guidelines published by several groups, including CPIC.  These tables are updated manually and therefore may not be current with recent changes in clinical guidelines, the FDA Biomarker Table or PharmGKB clinical annotations at the time of download.

This blog post has also been submitted as a comment to the open docket at FDA.

Announcing Dr. Kelly Caudle as co-PI of CPIC

CPIC is pleased to announce that Dr. Kelly Caudle (St. Jude Children’s Research Hospital) joins Dr. Teri Klein (Stanford University) as the co-Principal Investigator of the NHGRI U24 grant (HG 010135) that provides funds for CPIC.

Dr. Caudle has been the CPIC Coordinator/Director for CPIC for 8 years. During this time she has overseen the CPIC guideline development for 22 CPIC guidelines and 13 guideline updates and has led several CPIC projects. We thank Dr. Mary Relling for her outstanding leadership and we are thrilled that she continue her involvement in CPIC as a co-Investigator at SJRCH.

Congratulations, Dr. Caudle!

Join the new PGRN society!

After 20 years of NIH funding, the Pharmacogenomics Research Network (PGRN) is transitioning to an independent, nonprofit scientific society, and all interested individuals are invited to sign up to become a member of the new PGRN!  The independent scientific society will continue many of the functions of the current PGRN, and we encourage you to join today to stay involved.  Benefits of joining the new PGRN include:

•         Reduced registration fees for PGRN meetings and workshops, including member receptions and poster sessions at annual meetings with large scientific societies such as ASHG and ASCPT

•         Participation in member calls/webinars and Research in Progress Seminars

•         Membership on PGRN program committees for meetings and workshops

•         Network with colleagues and establish collaborations

•         Leadership opportunities for members (e.g., serve on PGRN committees, board, and as leaders)

•         Awards for trainees and mentorship opportunities

•         Access to PGRN web pages highlighting pharmacogenomics tools and resources, events and other useful information for PGx research, education and clinical practice

Special membership rates are available for trainees, multi-year memberships, early sign ups and those from developing countries. In addition, take advantage of the opportunity to be listed on the PGRN website as a founding member if you choose that option during signup. Sign up today at https://pgrn.regfox.com/pgrn-membership-dues.