Friday, May 26, 2017

Brief Blog: Breaking The Box in Genomic Research Paradigms: DecipherGRID

An article in this week's New England Journal, written by an international consortium (here), focuses on the global data for widespread data sharing in genomic cancer research.   They summarize the needs and goals, as reflected in programs like Cancer Moonshot.  

An innovative approach to shared genomic research resources appeared as Zhao et al. earlier this month in JAMA Oncology (here).    The authors took the concepts of luminal and basal gene expression or differentiation - as long used in breast cancer - and applied it to prostate cancer, with significant results.  (These panel-based classifications may prove clinically impactful for prognosis-dependent management and in predicting responsiveness to androgen deprivation drugs.)

However, a very interesting aspect is how they did it: with large gene-chip archives of data developed by San Diego's commercial firm GenomeDx through the DecipherGRID program.

GenomeDx has commercialized a prognostic prostate cancer test which has Medicare coverage.  In addition, GenomeDX uses a methodology which has also archived genomic data on 46,000 coding and non coding genes through array technology - the DecipherGRID program (homepage here.)  Researcher can collaboratively test hypotheses on the data - and many dozens of publications have already appeared.

Additional coverage of the Zhao et al. paper at Genomeweb here., and Genomeweb coverage on the DecipherGRID program here.

DecipherGRID data archives have also contributed to a major article on prostate cancer radiation sensitivity (research in Lancet Oncology here, press here.)




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For an article on coverage issues for prostate gene panel tests, see Managed Care, May 2017, here.  For example, a couple years after launch, the Myriad Prolaris test conducted for prognostic classification on biopsy tissue received relatively narrow coverage from Medicare MolDx (October, 2014; here);  which was expanded considerably over 18 months later (May 2017; here).

Thursday, May 25, 2017

SF's Genome Medical Raises $12M for Telemedicine Genetic Counseling

One of the challenges with the rapid growth of genetic testing is the shortage of genetic counselors.  Genome Medical, a San Francisco start up, aims to address this by rapid development of high-quality telemedicine services.

The startup has raised $12M in recent months from major investors such as Illumina Ventures, Canaan Partners, and others.   The company is founded by Randy Scott (previously involved in founding both Genomic Health and Invitae, which have a combined market cap of $1.3B), Lisa Alderson, and Harvard Medical School geneticist Dr. Robert Green.
  • CNBC story, here.
  • Genomeweb, here (brief).  Genomeweb subscription deep dive, here.
  • Genome Medical website, here.
In January 2017, Invitae acquired the patient-centered data information company AltaVoice (here).  Invitae also has collaborations centered around the Illumina spinout Helix (here) and Invitae announced a new exome service in March 2017 (here).   (Illumina has a current market cap of $25B).


Legal Case Filed Against Market-Moving CMS Information Leaks - Blaszczak et al.

According to multiple news reports on May 24, SEC has filed against an insider-trading scheme driven by CMS information leaks to a consultant for hedge funds.   The alleged actions in the case date back to 2012/2013.
  • The 51-page complaint, SEC vs Blaszczak et al., is online at SEC.gov, here.
  • New York Times, here.
  • Reuters, here.
  • Bloomberg, here.

Public information on the case is not new, with news stories dating at least to October 2014 (WSJ 2014 here.  Reuters 2014 here.)  

Sound bite from Bloomberg:
     A wide-ranging U.S. probe into under-the-radar information links between Washington and Wall Street snared three hedge fund executives, a D.C. consultant and a government employee, who are accused of profiting off inside information about changes in health-care regulations.
     The prosecution takes aim at the political intelligence industry in Washington, in which consultants -- often former government employees themselves -- nurture ex-colleagues for information about potentially market-moving decisions, and relay that to hedge fund traders and others in exchange for lucrative consulting fees.
     That’s what prosecutors in Manhattan accused three partners at Deerfield Management, a Centers for Medicare and Medicaid Services employee and David Blaszczak, a former CMS worker with his own D.C. consulting firm, of doing.
Linked-In for Blaszczak here.

Tuesday, May 23, 2017

Landmark FDA Approval Based on Tumor Gene, Not Tissue Type (Mismatch Repair, Keytruda)

In a landmark FDA approval, Keytruda has been approved based on expression of a mismatch repair gene, rather than on a tissue type such as colon cancer or lung cancer.    For additional coverage, see MedCityNews, here.  FDA press release here.  Reuters here, MedPageToday here.   Forbes here.  Genomeweb here.

Four weeks ago, this blog emphasized the growing buzz around total mutational burden, or TMB, which is often triggered by defective DNA repair in cancers (here).

In February 2017, Genomeweb reported that Personal Genome Diagnostics (PGDx) in Baltimore had landed an NIH grant to develop a TMB test on circulating tumor DNA.

An excerpt from MedCity News below:

   Colon, pancreatic, stomach, or ovarian cancer; it increasingly shouldn’t matter. In an era of precision medicine, the treatment approach should reflect the genetic makeup of the person’s tumor and the presence or absence of key biomarkers.
   That ethos was set in stone on Tuesday, with the landmark FDA approval of Merck’s checkpoint inhibitor, Keytruda (pembrolizumab), for patients with solid tumors that express so-called mismatched repair genes.
   In a statement, FDA noted the historic nature of its decision. “This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.”
The approval is an accelerated approval, meaning that it can be subject to eventual re-review on the basis of required additional studies.

Monday, May 22, 2017

Trade Press Summary: Color Genomics Pivots Towards Payers

A detailed subscription-only article at Genomeweb on May 22 discusses Color Genomics' new strategy to begin directly contracting with, and billing, major payers (here).  Color provides a 30-gene test that brings together genes for risks associated with eight common cancers (breast, prostate, etc).  The test's price point has been $249.  Genomeweb also has a short public-access summary, here.

The company raised a new funding round of $45M last September (here, here.)
  • For an open access trade journal on new-news regarding Color and payers, see MedCityNews, here.
  • For an open-access publication on its test in Breast Cancer Research and Treatment (dated June 2017), here.
  • For a 6-page white paper on its test on the company's own website, here.
  • The company made a switch among founders between Chairman and CEO in December, here.
  • For a look-back on the company's history by SF Biz Journal, here.
  • For a trade journal review of three companies (Grail, Twist, Color), see here.
  • For a commercial market report on the growing global predictive testing marketplace, here.
  • For an article on another innovator in the space, see MedCityNews on TrueHealth, here.

Chief Medical Officer Jill Hagenkord MD has worked successively at Complete Genomics, Invitae, UCSF, 23andMe, and Color (here).  More after the break.

Thursday, May 18, 2017

MolDX Issues Draft LCD: Covers Liquid Biopsy in Selected Lung Cancer Patients (Guardant360 Coverage)

On May 18, 2017, the MolDX program released a draft LCD that would provide coverage under several special conditions for a gene panel somatic mutation liquid biopsy test in lung cancer.

The LCD is online at CMS here or in the cloud here.


The proposed policy provides coverage in circumstances when an invasive biopsy is medically contraindicated or quantity-of-tissue failed to be sufficient for necessary genomic profiling.  The LCD cites 2017 NCCN guidelines that when tissue biopsy is unenviable, plasma genomic profiling should be considered.  The comment period runs from June 5 to July 20.

Guardant Health has had several successful funding rounds, totalling $550M, according to Forbes, here.  Its liquid biopsy test has also been recently approved by the New York Clinical Lab Evaluation Program (here).

See also a general article about liquid biopsy in Genetic Engineering News, here. Coverage of the new LCD at Genomeweb, here.  Press release here.  More after the break.

Wednesday, May 17, 2017

Brief Blog: Humor: "Clone Wars" As a Metaphor in Oncology

Someone recently pointed me to an article on "Clone Wars" in oncology and the genomic evolution of tumors.

The term has some history.  That are about ten hits on PubMed specific to "Clone Wars" in oncology, and they date back to 2006.   A search for oncology + cancer + "clone wars" on Google pulls up additional hits, such as a 2013 webpage at MD Anderson (here), and a deck by ASU's George Poste (here).

For the most prominent recent article, see Beltran's article The Clone Wars in Science Translation Medicine in February 2017 (here).   For an open access example, see Worsley et al. 2016 (here).

More examples after the break.

Brief Blog: Real World Evidence: An Emerging Mini Industry

The term real world evidence, supplemented by the term pragmatic trials, has been around for some years, but remains on an upswing.  Pubmed gives over 400 hits for "real world evidence," including a dozen articles currently "in press" (as of May 2017) in Journal of Clinical Epidemiology (here).  "Pragmatic trials" has 350 hits.

The specialists at EyeForPharma recently held a conference on RWE in Amsterdam in April 2017 and provide a long synopsis online, here (archive here).  The April 2017 agenda is still online, here.

They've also set up a webpage for a forthcoming November 2017 Philadelphia conference, here.




Saturday, May 13, 2017

Brief Blog: CMS Posts All Agenda Files for May-June HCPCS Meetings

CMS has posted all files for its May 16-17-18 and June 7-8 HCPCS code application meetings.   By law, CMS must post agendas for all applications, explaining the applicant's position, the CMS response, hold a public meeting, and post a final decision in the fall with response to comments.

The May 16-17-18 meetings are on drugs; the June 7-8 meetings are on DME and related supplies and equipment.   Generally, applications for major intravenous or physician-administered drugs zip right through.  Everything else has a low chance of being accepted (maybe 5%?)   For example, Medtronic applied for new coding for its 670G artificial pancreas, a widely praised achievement, but CMS turns down its application for a new code.   (Medtronic and stakeholders can attend the meeting and try to convince CMS otherwise.)

Links to the meeting registration (closed for May events; open til about May 20-24 for June events) are posted here:  https://www.cms.gov/Medicare/Coding/MedHCPCSGenInfo/index.html  

The events will be webcast live (exciting!!) - see links at page above.

Agenda items as PDF files are listed here for each of the five days, or in one zip file in the cloud here.

Drug and biologicals have 15, 13, and 11 agenda items (May 16-18), and DME and supplies have 17 and 18 agenda items (June 6-8), or  74 HCPCS agenda items in total. Some represent clusters of several related code items.


Thursday, May 11, 2017

Guardant Health Raises $360M

News today that Guardant Health, a Redwood City innovator lab focused on liquid biopsy, has raised a new round of funding for $360M.   This brings its total fundraising effort to $550M.

Open access news coverage at Forbes here.  And at MedCityNews here.

Investors include SoftBank, T Rowe Price, Temasek, Khosla Ventures, Lightspeed, Orbimed, and 8VC.  

Projects include liquid biopsy for driver gene diagnostics in patients with solid cancers and Project Lunar, which will focus on detecting the existence or reappearance of residual disease.

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Other recent fundraising in this space includes $60M for startup Freeome and $900M for Illumina spinout Grail.





Wednesday, May 10, 2017

Brief Blog: BCBS-Mass - An Unusually Broad Cancer Gene Panel Testing Policy

A colleague today pointed me to BCBS Massachusetts online medical policy (#790) for tumor gene panels - online here.  If I'm reading the title correctly, it's a broad policy for most members in HMO/PPO plans, as well as Medicare Advantage HMO and Medicare Advantage PPO.

The policy cites underlying New England Medicare LCDs for gene panel coverage in lung cancer and in AML.  However - and this caught me by surprise - it seems to go much further in its coverage of additional solid cancers and additional hematopoetic cancers than do the Medicare LCDs it cites.

The BCBS policy is worth a close look.  It has a brief prologue of text before it presents several gene tables and diagnosis panels.  Later (after pages of ICD-10 listings) there are several pages of additional text analysis and discussion (don't miss pp. 16-18).
Allowable solid cancers for gene panel testing include: bladder, breast, cholangiocarcinoma, colorectal, endometrial, GI stromal, glioma, medulloblastoma, melanoma, meningioma, neuroblastoma, NSCLC, rare tumors with < 5000 incidence, stomach, esophageal, thyroid, and unknown primary.  B cell and T Cell NHL appear in both the solid tumor and hematopoetic tables.  Other blood conditions include AML, B-ALL, T-ALL, plasma cell dyscrasia, myelodysplasia, Myeloproliferative disorder.

Brief Blog: FMI Releases Earnings Report (May 9, 2017)

FMI released quarter earnings and held its investor call on May 9, 2017.   The press release is here, the earnings call transcript is here (with some technical problems), and the full SEC quarterly report is here.  The webcast is archived here.  Coverage at Genomeweb is here.  This week share price fell from about $36 to $33 before settling around $34.50.

Clinical cases were nearly 14,000 for the quarter, up 55% year-on-year.   However, revenue per case was $2,700, against a recently established CMS price of $3,416.   (FMI had not been paid by the MAC in its home jurisdiction, Massachusetts, and opened a new lab in a different MAC territory, in North Carolina under PalmettoGBA.)

Hematopoetic test volume was down.

While clinical case volume was up 55% by quarter year-on-year clinical test revenue was up only 14% ($10.2M > $11.6M).  Further discussion after the break.


Monday, May 8, 2017

Brief Blog: CPT Agenda for June 2017 in Boston

The agenda for the June 2017 CPT Editorial Panel meeting in Boston has been posted, here.

According to an online AMA calendar, the agenda was posted on March 29.  That's important, because non-pathology public comments were accepted until May 19, eleven more days.  But MoPath comments were accepted only until April 7, and other lab comments til April 14.  Those dates are past.  (Circle your calendar now for July 13, so you can see the September CPT agenda while there's still time to comment in mid summer.  Take your laptop to the beach...)

There are about 40 non lab agenda items.  There are 6 MoPath items and 3 other lab items.

WIth the agenda numbers in parenthesis, the MoPath items are (#15) TFGBI in corneal dystrophy, (#16) EZH2 for hematologic neoplasms, (#17) BTK and PLG2 variants for CLL, (#18) Sept9 Promoter Methylation Analysis [revision], (#19) Tier 2 codes for PRAME and LINC00518, (#20) panel code for panethnic carrier screening.

Others include (#21) Rapid GI Pathogen target testing, and of general interest, (#39) Cat III code for HPV extended genotyping, and (#6) revisions to the FNA procedure codes.  Very few lab codes ever appear in Cat III.

Telemedicine

CPT will take 4 G codes created by CMS for telemedicine and convert them into CPT codes in the 99XXX series.   When this happens, CMS generally deletes the corresponding G codes.

Category III

Despite the continued rarity of most Category III codes in CMS utilization databases and the reputation for poor payment by commercial payers as well, there are 12 Cat III applications.  One of the applications is for a set of 5 codes to reflect behavioral counseling through an online diabetes prevention curriculum.  In total, almost 500 Cat III codes have been issued by AMA, though many of the earlier ones have been sunsetted.

Thursday, May 4, 2017

MolDX Issues New Draft LCDs for June 2017

On May 4, 2017, MolDx issued six new draft LCDs.

To access, go to the MolDx website here and click on "Draft LCD Status Report."  When you get to the resulting table, click on "comment period start date" to sort for the new June LCDs.

Topics include:
  • DL37264, EndoPredict Breast Cancer Gene Expression
  • DL37266, AlloSure Donor Derived Cell Free DNA Test
  • DL37330, Foodborne GI Panels Detected by Multiplex nucleic acid amplification tests (NAAT)
  • DL37258, Respiratory Viral Test Panels by NAAT
  • DL37260, Prometheus IBD-SGI Diagnostic Policy
  • DL37262, Oncotype DX Prostate for Men with Favorable Intermediate Risk for Prostate Cancer
Comment periods open June 5 (when Palmetto holds its public comment session) and close July 20.

PDFs filed in one cloud Zip file, here.

Very brief summaries are below.  For full details, see each LCD.
  • Endopredict, recently licensed in the US by Myriad, is covered in ER positive, Her2 negative breast cancer (0-3 nodes).
  • Allosure looks at cfDNA leaked by transplanted kidneys under immune attack; it is covered with ongoing clinical trial and outcome requirements.*  Stock price rose +40%.
  • The Oncotype DX prostate policy extends defined coverage into intermediate risk populations.
  • GI organism panel tests get detailed rules for limited coverage.  A number of test brands are cited (Hologic, BD, Nanosphere, Luminex, Biofire).
  • The respiratory panel LCD "is a non coverage policy for multiplex PCR respiratory panels." Luminex, eSensor, and Biofire panels are cited.
  • The Prometheus IBD sgi test policy is non-coverage.
Myriad has reported that Endopredict "significantly outperforms the first generation test," here.

CareDx's stock price opened Thursday at 87 cents, rising as high as $1.65 before closing at $1.20, +40%.   Market cap at close of day was $26M, suggesting about a $10M rise in market cap for the day.


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* Based on changes in the past six months, the LCDs do not describe "coverage with data development" or "coverage with evidence development" (here) but MolDx LCDs may state that certain published studies with certain clinical outcome parameters will be expected - as in the AlloSure policy.

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LCDs have a minimum comment period of 45 days.  There is no minimum or maximum time for additional contractor review after a comment period.  LCDs become effecdtive after a final version is posted plus another 45 day notice period.  Online manual here.

MACs "shall" hold an open public meeting for comments, and shall hold these before their CAC meeting, and shall allow interested parties including providers and manufacturers, to make presentations.  I thought that the LCDs must be posted some period (10 or 20 days) prior to the meeting, but I don't find that enumerated in the manual (13.7.4.1(d)).  It would be perverse, say, to require registration 7 days in advance but announce LCDs 1 day in advance - but I don't see a written rule about this in the current manual.

Brief Blog: US Public, Private Spending on Healthcare Compared to Other Advanced Countries

At the interesting website Visual Capitalist, they ran a March 2017 article on how US public and private healthcare spending stacks up to other advanced countries.

Here's a version of the metrics I hadn't seen before.  I'm simplifying - for details see the original blog.  Roughly, per-citizen, advanced European countries spend about $4000 on publicly funded healthcare and $1000 on privately funding healthcare.  The US spends $4500 on publicly funded health care PLUS $5000 on privately funded healthcare.

See the original charts and discussion here.

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For one of the most interesting recent US proposals - Medicare Advantage Premium Support for All or MAPSA - see Billy Wynne's blog here.

Wednesday, May 3, 2017

Brief Blog: Stanford 2017 Conference on Big Data and Biomedicine

This year's annual Stanford Conference on Big Data in Biomedicine will be held on May 24/25 on campus at Stanford.  Last year's conference drew 500 attendees in person and another 2000 by video.

Press release here; conference website here, the two-day agenda here.

Wednesday's agenda includes a keynote by Eric Topol of Scripps; update on the Precision Medicine Initiative; and panels on cardiovascular big data, regulatory sciences, AI, and the Chan Zuckerberg Initiative (big data in multiple fields, supported by Mark Zuckerberg).

Thursday's agenda includes panels on cancer, clinical trial observational big data, as well as a section on "digital health and technology."  Registration is $800.



Brief Blog: Duke Margolis Center & Critical Path Institute: Biomarkers in Washington - June 14-15, 2017

On June 14-15, 2017, the Duke-Margolis Center for Health Policy and the Critical Path Institute will host a two-day conference on regulatory validation of biomarkers.  The meeting is in Washington, DC.

No-cost registration is currently open online and is offered as both on-site and webinar registration.   For details click here.


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Two other upcoming conferences include an international tumor heterogeneity conference in Washington May 11-13 (here) and a San Francisco conference on liquid biopsy June 21-23 (here).  The latter coincides with the annual BIO conference in San Diego, June 19-23.