It’s beyond theory.  The microbiome is one of many trends that align well with the IVD market.  It is explored in Kalorama Information’s study of the in vitro diagnostic market, The Worldwide Market for In Vitro Diagnostic Tests along with other trends such as automation and gene editing.   The continuous search of the etiology of diseases as part of the body’s systemic response to change has led to a consideration of the gut microbiome as part of disease processes.  While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Bacteria in the gut, mouth and plaque (biofilms) have been implicated in a number of diseases including diabetes, obesity, autoimmune, cancer, diarrhea, and mental disorders.  Thousands of species of microbes—bacteria, viruses, fungi, and protozoa—inhabit every internal and external surface of the human body.  The microbiome’s complicated relationship with its human host is increasingly considered crucial to health.  Imbalances in the microbiome’s diverse microbial communities, which interact constantly with cells in the human body, may contribute to chronic health conditions, including diabetes, asthma and allergies, obesity and the metabolic syndrome, digestive disorders including irritable bowel syndrome (IBS), and autoimmune disorders like multiple sclerosis and rheumatoid arthritis.

The microbiome skincare market is expected to continue to grow by double digits in every country researched (United States, Germany, Korea, Japan, Thailand, and China).  The primary drivers for its growth are the natural wellness trend, the fear of chemicals, increasing influence of environmental stressors, and pharmaceutical company investment.  In fact, recent television ads for skin care soaps in N. America state the product “keeps the skin’s natural microbiome intact.”  There are of course probiotics and books that direct consumers to maintain a healthy gut for overall wellness.

While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Intense research into the relationship of a person’s population of normal flora and pathogenic invaders with the etiology and progression of disease states has been developed into microbiome-based molecular tests.  Some IVD companies are already developing a greater appreciation for the microbiome’s contributions to human biochemistry and have launched tests to measure changes in the microbiome to monitor disease progress.  At this time, most testing is available from service providers and for research.  There are however at least two CE Marked test kits available from Genetic Analysis (Oslo, Norway) and Luxia Scientific (France)

Researchers also evaluate specific diseases associated with disturbances in the microbiome, including gastrointestinal diseases such as Crohn’s disease, ulcerative colitis, irritable bowel syndromes, and obesity, as well as urogenital conditions, those that involve the reproductive system, and skin diseases like eczema, psoriasis, acne, obesity, diabetes, autoimmune disorder, acute diarrhea, cancer, mental disorder, and others.

Of interest are the CE Marked tests from Genetic Analysis (Oslo, Norway).  Genetic Analysis was awarded the CE Mark for its Dysbiosis test for microbiome imbalance in irritated bowel syndrome.  Genetic Analysis has developed GA-map technology, the first gene-based routine test for the mapping and aide in diagnosis of diseases associated with dysbiosis and imbalances in the bacteria in the digestive system.  Genetic Analysis was established in 2008 and is based on research done by Professor Knut Rudi at Norwegian University of Life Sciences.

In 2018, Luxia Scientific (Paris, France) was awarded the CE Mark for its 1test1 that analyzes the bacterial content of the gut microbiome.  Leveraging 16S rRNA sequencing, it provides information about bacterial diversity and the relative abundance of many bacterial groups that provide beneficial health benefits, (according to Luxia).   In March 2018, Luxia announced an exclusive distribution agreement with Life Genomics (Sweden) whereby Life Genomics will exclusively distribute Luxia’s 1test1 test in Sweden, Denmark, Finland, Iceland, and Norway.

Other IVD industry initiatives include:  OraSure Technologies (Bethlehem, PA) is best known for its point-of-care diagnostic tests for infectious diseases and molecular sample collection devices.  In January 2019, OraSure acquired CoreBiome (St. Paul, MN) an early-stage microbiome services provider for customers in the pharmaceutical, agricultural, and research communities.  The company’s slogan is “Powering microbiome science with big data”.  CoreBiome’s technology provides information-rich characterization of microbial diversity and function, paired with machine learning and expert analytics.  CoreBiome’s BoosterShot platform allows researchers to efficiently run high-resolution DNA sequencing on thousands of microbiome samples.  OraSure indicated that CoreBiome’s microbial genomics technology will complement the company’s DNA Genotek’s molecular sampling business.

Bio-Rad Laboratories entered into a collaboration with Genetic Analysis AS (Oslo, Norway) and Bioaster, a French microbiology research institute, to study gut microbiome alterations in metabolic disorders.  The project will look for microbiota signatures of dysbiosis in metabolic disorders like diabetes and obesity in order to pursue diagnostics development.  It will use Bioaster’s deep and 16S-targeted sequencing technologies and advanced pipelines of data analysis for highlighting new gut microbiome biomarkers, according to a statement.

Bio-Rad acquired the distribution rights for the CE Marked GA-Map test made by Genetic Analysis (Oslo, Norway).  The assay tests for gut microbiota and detects bacterial imbalances to diagnose and manage conditions such as inflammatory bowel disease and irritable bowel syndrome to detect imbalances in the gut microbiome.  GA-map uses 16S rRNA amplification and a number of proprietary analysis technologies.

Thermo Fisher launched the Applied Biosystems Axiom Microbiome Array for simultaneous detection of archaea, bacteria, fungi, protozoa and viruses in human and non-human samples. Developed in collaboration with the Lawrence Livermore National Laboratory (LLNL), the array is designed to increase the understanding of microorganisms, while accelerating the translation of these insights into human health and agricultural applications.

According to Thermo Fisher, a major advantage of the array, which incorporates sequences for over 12,595 species in the National Center for Biotechnology Information (NCBI) archive, is the simultaneous detection of protozoa and viruses and ease of analysis, a capability that is not available with 16S or other platforms.  Most recently, the Axiom Microbiome Array won the R&D 100 Award, which honors great R&D pioneers and their revolutionary ideas in science and technology.  Awarded by R&D magazine, and considered the “Oscars of Innovation”, the R&D 100 Awards recognize and celebrate the top 100 technology products of the year.

While only two weeks of the first quarter of 2020 could truly be said to be under the grip of the U.S. portion of the COVID-19 pandemic and associated social distancing, companies with molecular diagnostic divisions reported a variety of positive results.  Kalorama expects further growth in the sector in Q2 reports and some tail off as immunoassay tests replace molecular, per Kalorama’s most recent report – COVID-19 Update: Impact on Molecular Markets…

We expect further growth in the sector in Q2 reports and some tail off as immunoassay tests replace.

  • Abbott Molecular Division (represents the m2000 SARS-CoV-2 Test) up 30%; Rapid Diagnostics (molecular point of care and other tests, including ID NOW test) up 5.7%. Large increase in shipments of m2000 test reported. Quarter reflected only a few days of ID NOW availability.
  • Hologic Molecular Diagnostics revenue increased 13.6%, or 14.2% in constant currency, the division’s highest growth rate since 2012. This included $3.4 million of sales from the Company’s Panther Fusion SARS-CoV-2 assay.
  •  Roche Molecular Diagnostics posted over 20% growth due to COVID-19.  Telling for other parts of the business:  Centralized and point-of-care , decreased 6 percent, its immunodiagnostics business declined 4 percent. Clinical chemistry sales were flat.

Smaller companies benefited from the general trend of positive results for COVID-19 testing increases.

  •  Twist Bioscience reported that revenues were up 42% – The company launched methylation product for next-generation sequencing.
  • T2 Biosystems Q1 Revenues Jump 43 Percent – In the quarter T2 signed a licensing agreement for SARS-CoV-2 assay development and a purchasing agreement with Vizient.
  • GenMark Diagnostics Q1 Revenues Grow 80 Percent -The company’s revenue growth was driven by increasing sales of its ePlex molecular diagnostics analyzer, which now has a SARS-CoV-2 test.

Companies with life science divisions suffered because of research lab closures.  Kalorama covers these trends and more in its report on COVID-19 Impact on Markets.  The report can be found here: https://kaloramainformation.com/product/kalorama-covid-19-update-impact-on-molecular-diagnostics-serology-critical-care-tests-vaccines-and-telehealth-markets/

Demand for testing has gone from a healthcare industry topic to a national crusade in weeks with the onset of COVID-19. High-throughput tests have been approved by the U.S. Food and Drug Administration (FDA) for use in the U.S. for the detection of SARS-CoV-2, the virus behind the disease. But for true intervention in doctors offices — or even airports, many see so-called “point-of-care” (POC) IVD tests as the ideal solution.  A new report on worldwide point-of-care markets from IVD market researcher Kalorama Information has been released amid the coronavirus outbreak. The report has markets for all kinds of near-patient testing — everything from self testing for glucose to rapid HIV tests to cardiac marker tests. Yet the focus in recent weeks has been on tests for COVID-19. Point-of-care tests are tests designed to be portable enough and fast enough to be useful during an one visit or in a decentralized location within a hospital or clinic.

To break a transmission chain, fast access is needed. These tools offer fast access, rather than waiting on texts or doctor’s office staff for restults. Kalorama publishes a report each year on POC markets and has just released its 2020 version: https://kaloramainformation.com/product/the-worldwide-market-for-point-of-care-poc-diagnostics-7th-edition/.

In terms of actual tests for coronavirus tests, there are no U.S. approvals at the time of writing, but products are in development. Molecular POC (mPOC) tests make the most sense because the threat is a virus and can be identified using the gold standard of reverse transcription polymerase chain reaction (RT-PCR). Point-of-care tests are currently used for flu and step tests, including systems by Abbott (ID NOW), Roche (Liat), and Cepheid (Xpert Xpress) mPOC-maker Cepheid says it is developing an automated molecular test for the qualitative detection of SARS-CoV-2. And Cepheid says it will try to utilize its tens of thousands of existing instrument placements. “By leveraging the design principles of our current Xpert Xpress Flu/RSV cartridge technology, in which multiple regions of the viral genome are targeted to provide rapid detection of current and future pandemic coronavirus strains, we are developing a test that can be applied in multiple settings where actionable patient management information is needed quickly,” the company said.

Singapore POC maker Credo Diagnostics Biomedical announced this week that it has obtained the CE mark in Europe for an assay to detect SARS-CoV-2. The test runs on the firm’s platform, called VitaPCR, and the company said it uses PCR and runs the test in 20 minutes. The system needs minimal operator training to run and involves no additional equipment, according to Credo.

The company says the VitaPCR SARS-CoV-2 Assay is now also pending Emergency Use Authorization from the FDA and Emergency Use Listing from the World Health Organization.  While not as fast as immunoassays, the mPOC systems typically use isothermal amplification to achieve much faster turnaround than the regular lab-based RT-PCR tests. This is one of their biggest strengths, along with low. The following are some additional examples of molecular diagnostic systems and assays including POC and other technologies which are available or under development:

  • Aldatu Biosciences – PANDAA qDx SARS-CoV-2
  • Becton Dickinson (BD) – BD and BioGX submitted for EUAs on BD Max platform
  • BGI/ Pathomics Health – Fluorescent RT-PCR kit (CE marked); 2019-nCoV PMseq Kit
  • Bio-Rad – standards – synthetic COVID-19 RNA transcripts and human genomic DNA
  • bioMerieux/ BioFire Defense – FilmArray, BioFire COVID-19 Test
  • Biomeme – Go Strips for  COVID-19
  • BIONEER Corporation – AccuPower 2019-nCoV
  • Caspr Biotech – Phantom 1.0 Dx, disposable test usingCRISPR
  • Cepheid – Test in development for Xpert Xpress system announced; partnership for Sherlock Biosciences’ CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) engineering biology platform, to design tests to run on Cepheid’s GeneXpert systems
  • CerTest Biotec – VIASURE 2019-nCoV Real Time PCR Kit (CE mark for BD Max platform)
  • Co-Diagnostics – Logix Smart Coronavirus Disease 2019 (COVID-19) Test; single step rRT-PCR (CE mark)
  • Coyote Bioscience – Mini8 Portable Molecular Diagnostic QPCR Station (CFDA approved)
  • Credo Diagnostics Biomedical – VitaPCR platform, COVID-19 assay (CE mark)
  • Curetis/ OpGen/ BGI – RTPCR test kit for SARS-CoV2 (CE mark)
  • Diagnostics for the Real World Ltd – SAMBA II COVID-19 Test
  • GenMark – ePlex SARS-CoV-2 test; sample-to-answer system based on competitive DNA hybridization and electrochemical detection technology (RUO, with EUA submitted)
  • HiberGene – HG Swift, can use battery power, pursuing Fast Track Emergency Use in China
  • Integrated DNA Technologies (Danaher) – 2019-nCoV CDC EUA Kit
  • Jiangsu Qitian Gene Biotechnology Co., Ltd. – Fluorescent RAA Detection for 2019-nCoV
  • LabCorp – COVID-19 reverse transcription polymerase chain reaction (RT-PCR) test (EUA issued)
  • LGC Biosearch – primer and probe kits for CDC Real-Time RT-PCR Diagnostic Panel
  • MiCo Biomed Co. Ltd – VERI-QTM PCR 316 COVID-19 detection system
  • Mobidiag – Novodiag COVID-19 + InfA/B – multiplex test for coronavirus and influenza
  • Molbio – TrueLab, Truenat SARS CoV-2 – TruePrep and TrueNAT instruments
  • Mologic – battery powered point-of-need diagnostic test
  • Novacyt – qPCR (CE mark)
  • OnSiteGene – Peak V
  • Pinpoint Science – SARS-Cov-2 test in partnership with Analog Devices
  • Qiagen – QIAstat-Dx, Respiratory Panel 2019-nCoV
  • QuantuMDx – Q-POC
  • RainSure Bio – DropX-2000 Digital PCR System, RainSure COVID-19 dPCR Detection Kit
  • Randox Laboratories Ltd – Extended Coronavirus Array
  • Seegene – Allplex 2019-nCoV assay (CE mark)
  • Sentinel Diagnostics – Stat-NAT COVID-19 assay
  • SolGent – DiaPlexQ Novel Coronavirus (2019-nCoV) Detection Kit (CE mark)
  • Twist Bioscience – NGS-based target capture for SARS-CoV-2 detection and screening
  • Ubiquitome – Liberty16, open mobile real time PCR system with 2-3 hour battery life

 

In addition to direct tests for SARS-CoV-2, Kalorama expects demand for flu tests to increase due to “rule-out” testing.

Right now, molecular is the focus for the current pandemic, but immunoassays also are in development. Molecular tests generally analyze the viral RNA in patient throat/nasal swabs, but there are other POC testing methods that use immunoassays to detect the patient’s COVID-19 antibodies in blood or serum. It appears there are roles for both mPOC and immunoassay POC tests as there are trade-offs between the two. Immunoassays generally suffer from a high rate of false negatives (low sensitivity), with some rare exceptions. Nonetheless, immunoassays can have comparable speci􀂦city and a varying combination of lower cost, faster turnaround, greater portability, and, thus, advantages in the context of larger-scale population surveillance, screening, and triaging of patients in outbreak situations.

About Kalorama Information

Not since the Swine Flu epidemic of 2009 has there been this amount of emphasis on vaccines and vaccine development.  This new infectious disease threat with no anti-viral, nor vaccine is causing significant concern among healthcare providers, governments and the public.  Last-resort measures such as school closings and curfews in place in the United States has only increased focus on a vaccine solution that could provide enough protections to individuals.

Kalorama covers vaccines markets from 2018 to projected 2024 markets in its market research study: https://kaloramainformation.com/product/vaccines-2018-world-market-analysis-key-players-trends-pediatric-and-adult-segments-influenza-cervical-cancer-combinations-hepatitis-pneumococcal-mmr-varicella-poliovirus-hib-others/
A new report will be out in July 2020.

Some diseases have proven extremely difficult to address through vaccines – HIV, for example. However, although much is unknown about COVID-19, it is nonetheless a respiratory disease that belongs to a class of diseases – corona viruses – that is well understood.  This provides more confidence

We talked with our vaccine analysts to get their sense of the landscape with novel coronavirus.

Early Efforts and a First Trial Dose

COVID-19 vaccine candidates are now heading into trials. Companies in various stages of development include Gilead, GlaxoSmithKline, Pfizer, Moderna, Medicago and others.

Pfizer chairman and CEO Dr Albert Bourla said: “Many companies, including Pfizer, are working to develop antiviral therapies to help infected patients fight this emerging virus as well as new vaccines…Pfizer is working to advance our own potential antiviral therapies and is engaged with BioNTech on a potential mRNA coronavirus vaccine.”

Cambridge, MA-based Moderna announced first participant dose in a Phase 1 trial for mRNA-1273 against the novel coronavirus.  Moderna’s mRNA-1273 is an mRNA vaccine against SARS-CoV-2 encoding for a prefusion stabilized form of the Spike (S) protein. The company’s Phase 1 study is evaluating the safety and immunogenicity of three dose levels of mRNA-1273 (25, 100, 250 μg) administered on a two-dose vaccination schedule, given 28 days apart. A total of 45 healthy adults will be enrolled in the study. Participants will be followed through 12 months after the second vaccination. The primary objective is to evaluate the safety and reactogenicity of a two-dose vaccination schedule of mRNA-1273. The secondary objective is to evaluate the immunogenicity to the SARS-CoV-2 S protein.

This is a major opportunity for vaccine developers, so it is likely that if a developer has a vaccine  that could be even partially effective, they will do everything possible to move it thru trials quickly.   At the same time, governments are looking for more tools to contain the spread. It’s clear that steps taken to date have not been sufficient.   So they are highly motivated to support vaccine development efforts.

Technology 

Demand is not the issue, according to Kalorama’s vaccine analysts.  The market pull will be there, but in vaccine markets, where customers are generally governments, it comes down to the technology – the products.

Some diseases have proven extremely difficult to address through vaccines – HIV, for example. However, although much is unknown about COVID-19, it is nonetheless a respiratory disease that belongs to a class of diseases – corona viruses – that is well understood.  This provides more confidence that it is possible to create a vaccine that would protect some portion of the population.

Since other countries do have significant vaccine development resources – China, India, Japan, etc. – it is certainly possible that a vaccine could be developed overseas before one is developed in the U.S. In fact, I would guess that Chinese vaccine developers began working on this weeks before U.S. vaccine developers.

The Gaurdian reported that about 35 companies and academic institutions are racing to create such a vaccine, at least four of which already have candidates they have been testing in animals.

Stat News reported about an interesting synthetic mRNA solution that is being developed.   https://www.statnews.com/2020/03/11/researchers-rush-to-start-moderna-coronavirus-vaccine-trial-without-usual-animal-testing/ that would be “programmed with the goal of getting our inner machinery to produce certain coronavirus-like proteins — the very proteins that the pathogen uses to gain entry into our cells. Researchers at Moderna and the NIH think that once those homemade dummy virus particles are there, the thinking goes, our bodies will learn to recognize and clobber the real thing.”

Production

Of course, developing a vaccine is only part of the problem. Any vaccine would have to be effectively manufactured and distributed. That could create significant roles for many other players.

Most inactivated influenza vaccines are produced by growing influenza viruses in eggs.  This requires a staggering amount of them. For the H1N1 flu vaccine, a million eggs are required for 3 million doses, more or less.

Egg-based production process begins with candidate vaccine viruses (CVVs) grown in eggs provided by the CDC or approved partner per current FDA regulatory requirements. These CVVs are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate. The fluid containing virus is harvested from the eggs.

Cell-based flu vaccine has been developed as an alternative to the egg-based manufacturing process. On August 31, 2016, FDA issued an approval for Seqirus, the sole FDA-approved cell-based flu vaccine manufacturer in the United States, to begin using cell-grown CVVs.  Cell culture technology is potentially more flexible than the traditional technology, which relies upon adequate supply of eggs. Recombinant DNA manufacturing is another option. This method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. Instead, manufacturers isolate a certain protein from a flu virus. This proteins are then combined with portions of another virus that grows well in insect cells and allowed to replicate. A protein is harvested from this mix that is used to make the vaccine.

According to a recent article in the Los Angeles times, there are many different vaccine-making platforms, each with its own set of advantages and disadvantages. https://www.latimes.com/science/story/2020-03-12/why-does-it-take-so-long-to-make-a-coronavirus-vaccine “For example, a vaccine based on the virus’ genome can be made quickly, in perhaps a month or two, but it may be harder to manufacture in giant quantities. Another option is to take the virus’ genetic snapshot and put it into a different virus for transport. These vaccines take longer to make — say, six to eight months — but they can be scaled up more readily.”

” almost 33% of readers believe it will take over a year, while slightly more 28% are optimistic there could be a vaccine available within three months.” -Pharmaceutical Technology

An article in Pharmaceutical Technology  said that “Readers of Pharmaceutical Technology have been voting on how long they think it will take for a vaccine to be available to patients. With over 164,000 votes cast, the results show than almost 33% of readers believe it will take over a year, while slightly more 28% are optimistic there could be a vaccine available within three months.”

In general,  this is a very major opportunity for the vaccine industry to shine.  We would expect it to rise to the occasion with at least one, if not several, potential products.  Kalorama will of course report on updates in our biennial vaccine market research study.

 

A rapid scale-up of diagnostic testing for the novel coronavirus was the focus of a declaration of emergency by President Donald Trump in a March 13 press conference. The plan calls for sharply boosting the production of coronavirus test kits while also making tests available at a network of drive-through sites.

In an address at the White House Rose Garden, Trump announced a series of sweeping measures designed to eliminate government regulations that may have been hindering the federal response to the coronavirus outbreak. Most of Trump’s address was devoted to the administration’s plans for making diagnostic testing more available across the country — an issue that has become a flash point for criticism of the administration’s response to the virus.

In his emergency declaration, Trump said that previous government regulation included “very old and obsolete” rules. The new declaration would enable the U.S. Department of Health and Human Services (HHS) to waive rules that may have impeded hospitals and healthcare providers from responding adequately to the coronavirus outbreak. The declaration would also make available $50 billion in federal funding to fight the outbreak.

But Trump reserved the lion’s share of his speech to explain what the administration is doing to make diagnostic test kits more available to test for SARS-CoV-2. Healthcare providers and clinical labs in the field have complained that they have not had enough coronavirus tests available to meet demand, and some have claimed that testing criteria have been too restrictive.

The new plan relies on a combination of making more testing capacity available and at the same time making it easier for Americans to get tested, such as with drive-through testing sites. The administration is also working with Google to set up a website that will enable Americans to determine on their own whether they should seek out testing.

With respect to testing capacity, Trump explained the work the administration has been doing with diagnostics manufacturers such as Roche and Thermo Fisher that builds on a meeting between diagnostics vendors and the government last week.

Roche developed a high-throughput test for the coronavirus, cobas SARS-CoV-2, that received emergency use authorization (EUA) from the U.S. Food and Drug Administration (FDA) within 24 hours of submission of an application. The test’s high-volume capacity should be a step forward in meeting demand for coronavirus testing, Trump said.

FOR MORE INFORMATION

https://www.labpulse.com/index.aspx?sec=sup&sub=mic&pag=dis&itemid=800889

 

Molecular point-of-care diagnostic solutions offer improvements in the sensitivity and specificity of existing near-patient and rapid tests while expanding the diagnostic capabilities at points of care, such as hospital critical care units, physician offices, outpatient clinics, and community health posts in the developing world, and are used to assess conditions or admit patients.  The concept of molecular point of care is to mix the accessibility of POC testing with the accuracy of molecular technology. Kalorama has covered molecular point of care on a yearly or biyearly basis since 2013. Our latest report found slower system adoption, but brisk consumables sales and the continued hope of test menu expansion.

The molecular point of care segment, the focus of the report, includes only the small/ portable models and defines the molecular POC/ near-POC market as:

  • Systems that are CLIA-waived, or could soon have or potentially have the capability for running CLIA-waived tests.
  • Systems that can run moderate-complexity or high-complexity tests in a decentralized setting such as a non-laboratory area of a hospital or a physician office/ clinic visit.
  • Tests with a short waiting period for the results, making it practical and useful for POC.

This may differ from other definitions of point of care.  The mPOC systems have great sensitivity and scalability, and they won over early adopters but have had difficulty making the case for routine adoption.  As was asked at the Association for Molecular Pathology (AMP) meeting panels last year: Is the juice worth the squeeze? And there’s not a true answer yet. These systems will have to prove to gain new placements.

“Our latest report found slower system adoption, but brisk consumables sales and the continued hope of test menu expansion.”

The overall revenues estimate for this “true” mPOC segment is provided below. This segment is largely made up of tests for the flu and other respiratory diseases.    However, they are earning consumables sales from the placements they have.  As presented, the revenues for this segment are forecast to increase from $360 million to $852 million between 2019 and 2024, with a compound annual growth (CAGR) of 18.8%.

Kalorama also details another segment: more than $2 billion of “near-patient” systems that are not aimed at decentralized testing areas and require users to have technical competency.

Molecular systems need to prove marginal worthiness in the clinical setting as they have a higher cost.    Molecular tests tend to have much higher sensitivity and specificity, even 100%, but lab-based nucleic acid amplification tests were historically slower and required more expertise to run. Now with mPOC systems, the question will turn on marginal difference in sensitivity over immunoassay systems, and this will be driven by journal literature and clinical practice changes.

Justification for purchases of molecular point-of-care instruments and reagents are dependent on the argument of superior sensitivity and specificity. In this regard, the findings from a January 2020 Journal of Clinical Microbiology study are welcome news.  Major CLIA-waived mPOC systems were compared with immunoassay systems. Molecular had high-90s sensitivity, whereas the tested immunoassay system had high sensitivity of 80% and a sensitivity for influenza B of 67%. Not being able to establish a “true-negative” test has been a frustration of providers using rapid immunoassay tests.

 

March 9, 2020 — The revival of legislation to change the regulation of laboratory-developed tests (LDTs) has drawn a mixed response. The reintroduction of the Verifying Accurate, Leading-edge IVCT Development (VALID) Act is intended to remove barriers that are believed to have impeded the U.S. government’s response to the coronavirus epidemic.

The issue of diagnostics regulation has emerged as a political lightning rod, with some faulting the Trump administration’s response to the outbreak and others blaming what they claim is a history of federal overregulation of clinical labs.

“The industry associations that produce commercial IVD kits and pathologists who are concerned about overcommercialization of lab tests are clashing with representatives of the laboratories themselves.  These opinions represent longstanding positions of the players.”

Clinical labs are regulated by the U.S. Centers for Medicare and Medicaid Services (CMS) under CLIA and are not typically subject to oversight by the Food and Drug Administration (FDA). However, the FDA does regulate individual diagnostic tests, with diagnostic manufacturers required to gain FDA approval to market their assays. Yet another regulatory category, laboratory-developed tests, are tests that labs can develop and use on their own.

The situation has created several hurdles in responding to the novel coronavirus. When the FDA declared the coronavirus a public health emergency, it triggered a requirement that labs in the field get the FDA’s blessing to use their LDTs for the virus. The FDA subsequently waived this rule on February 29, but the need for a permanent solution to the regulatory environment is apparent…

To read more, please visit LabPulse.com: https://www.labpulse.com/index.aspx?sec=sup&sub=lab&pag=dis&ItemID=800854

 

coronavirus

The House of Representatives and Senate today passed an $8.3 billion spending package to help providers and local governments handle the spread of the coronavirus and to boost the development of vaccines and tests of the virus.  While vaccine support and spending on healthcare is expected, the bill also  boosts telehealth solutions with financial support and positive regulatory changes. 

Telehealth, or as Kalorama defines it, remote patient monitoring, is a $42-billion dollar market

The coronavirus response bill released by Congress on March 5th expands the Medicare reimbursement for  providers using who treat patients via telehealth to treat seniors at home.  The emergency spending bill waives Medicare’s geographical restrictions on telehealth during a public health emergency, enabling providers to use telehealth in both urban and rural areas as well as in the patient’s home as part of an “emergency area.”  Previously this was limited to rural areas.  It also loosens definition on telehealth devices, essentially allowing any device connecting physician and patient with audio and video capabilities.  This is a significant boost for telehealth and is understandable given the spread of the disease and the need to both service patients and protect physicians, nurses and other staff.

Most importantly, the bill contains mandatory funding authorization for $500 million over 10 years to be used toward a remote health care program.

This is a boost for the patient monitoring and telehealth market.  Kalorama Covers Remote Patient Monitoring in This Report: https://kaloramainformation.com/boost-for-42-billion-dollar-remote-patient-monitoring-market-in-covid-19-bill/

The global patient monitoring and telehealth market is estimated to be worth about $42 billion in 2019, inclusive of devices, peripherals, software, packaged services, monitoring services and other applications.  The market has benefited from the demand to move to a more wireless and streamline operation both within major health facilities and in-home treatment markets.  The demand to integrate data processing capabilities and EMR transfer options has also fueled the market.  There is also an increasing trend to upgrade to ambulatory and hand-held devices.

No longer is telehealth for rural patients alone.  For qualified providers, an emergency waiver will allow telehealth to be reimbursed by Medicare.   And extra funding is provided.

The interest in telemedicine and telehealth has exploded over the last decade.  Involvement in this care segment has several benefits and hospitals, caregivers, device manufacturers, and patients are continuing to jump on board with acceptance using this technology.  There are more than 700 clinical trials using telehealth recently completed, currently underway.  The global patient monitoring and telehealth market has continued its expansion in both the institutional and home segments of the health market with the United States and many European countries at the forefront of implementation.

 The industry spoke in the past few days and Congress listened.  In a recent letter sent to Senate Majority Leader Mitch McConnell, R-Kentucky, House Speaker Nancy Pelosi, D-California, and other Congressional leaders, the ATA – along with HIMSS, the eHealth Initiative, Health Innovation Alliance and Personal Connected Health Alliance – has asked Congress to make money from the COVID-19 supplemental appropriation available for more telehealth services.

Unique Opportunities in Telehealth/Telemedicine

There are a number of market opportunities in telemedicine that may offer some benefits over traditional office-based care.

For example, AMD Telemedicine’s General Exam Camera and Telephonic Stethoscope were used in a pilot program to treat Illinois inmates with HIV and Hepatitis.   Other examples include using telehealth to address the growing need for mental health monitoring and intervention.  This is an area where interest has increased significantly, as barriers to treatment are three-fold: lack of treatment resources; lack of adequate medical coverage; embarrassment.

Mental Health Assessment through Telemedicine

Telemedicine in the area of mental health disorders and conditions is often referred to as telemental health or telepsychiatry.

One area of mental health therapy is PTSD a type of anxiety disorder brought on by very traumatic situations such as war.

The costs of PTSD are difficult to accurately pinpoint because it may manifest itself in different ways for different people. Some patients seek therapy in unhealthy methods such as through alcohol and drugs. Lost wages, mortality, therapy sessions, physical health problems (non-psychiatric care), and prescription drugs are all costs associated with treating PTSD.

Caregivers may use telepsychiatry when they move or if the patient moves. Telehealth has the potential to increase the time a patient can see one caregiver, which has been linked to improved care, and can be beneficial for the worker who can keep some of their income after a move, even if it is only on a part-time basis.

Currently, in traditional fee-for-service Medicare, use of the telehealth benefit is limited to rural Health Professional Shortage Areas (HPSA1), CMS defined telehealth originating sites, and synchronous telehealth services. The Next Generation ACO Telehealth Expansion Wavier eliminates the rural geographic component of originating site requirements, allows the originating site to include a beneficiary’s home, and for the use of asynchronous telehealth services in the

specialties of teledermatology and teleophthalmology.

The waiver will apply only to beneficiaries aligned to a Next Generation ACO and for services furnished by a Next Generation Participant or Preferred Provider approved to use the waiver.  An aligned beneficiary will be eligible for the Telehealth Expansion Waiver if the beneficiary is located at their home or one of the Centers for Medicare & Medicaid Services (CMS) defined telehealth originating sites.

Medicare currently covers a limited number of Part B services delivered by an approved provider to a Medicare beneficiary. The beneficiary must be located in an approved “originating site” and services must be delivered by face-to-face consult using live video conferencing technology.   Originating site under existing Medicare telehealth rules include.

– Physicians’ or practitioners’ offices

– Hospitals

– Clinics and federally qualified health centers

– Hospital-based renal dialysis centers (including satellites)2

– Skilled nursing facilities (SNFs)

– Community mental health centers

There are a huge number of companies offering some form of wireless and remote technologies, patient data processing applications and equipment, and EMR data transfer equipment.  Competitors supplying patient monitoring and telehealth systems to hospitals are large, established healthcare companies, often working in conjunction with information technology (IT) companies on an entire system.  The home healthcare and other sectors are much more fragmented and are dominated by privately held companies.  In addition, some companies supply innovative products, but only for a small segment of the market; and some companies supply products on a regional basis only.

Although there are many participants in the market, a handful of companies continue to make a significant impact on the patient monitoring and telehealth technologies market.  The top five contributors to the market include:

  • Medtronic
  • Abbott Laboratories
  • Philips Medical
  • Boston Scientific
  • GE Healthcare

With the world’s major health organization upping the mortality rate to 3.4%, there is increased need for a working rapid test for COVID-19 to be able to properly isolate patients and protect providers.

The World Health Organization (WHO) has raised its estimate of the mortality rate of patients infected with the novel coronavirus to 3.4% globally, up from a 2.3% death rate in previous estimates.  In a press briefing in Geneva, WHO Director-General Dr. Tedros Adhanom Ghebreyesus told reporters of the higher mortality estimate based on reports coming in from around the world, according to an article on CNBC.com.

The novel coronavirus SARS-CoV-2 causes the disease COVID-19. As of March 4, 92,943 cases of COVID-19 had been reported globally, with 3,160 deaths, Ghebreyesus noted during a mission briefing on March 4. The WHO has shipped nearly half a million sets of personal protective equipment to 27 countries and has sent “hundreds of thousands of lab tests” to countries in call regions, he said.

The higher mortality estimate for COVID-19 represents a significant escalation of the health risk posed in the event that coronavirus infections spread significantly. Concern about the coronavirus outbreak has already resulted in the cancellation or postponement of public events scheduled for March, such as the European Congress of Radiology in Vienna and the Acute Cardiovascular Care conference in Athens.

By point of comparison, the mortality rate from the seasonal influenza virus is around 0.1% in the U.S., according to published sources.

In the press briefing, WHO officials said that much of the difficulty in estimating the health impact of the novel coronavirus comes from the fact that the virus behaves differently from the flu virus, and the mechanisms by which it is transmitted aren’t fully understood, according to the CNBC report.

On the positive side, they said that in countries with “strong measures” to contain outbreaks, virus transmission can be suppressed.

Please sign up to our sister publication, www.labpulse.com for more information on this disease.

Adding a fifth “vital sign” — that is, travel history — to patient intake evaluations could go a long way toward identifying those at risk of the COVID-19 coronavirus disease and potentially slow its spread, according to a commentary published March 2 in the Annals of Internal Medicine.

A typical patient evaluation includes an assessment of temperature, heart rate, respiratory rate, and blood pressure. But in the context of COVID-19, adding travel history is key, wrote a research pair led by Dr. Trish Perl, chief of the division of infectious diseases at the University of Texas Southwestern Medical Center.

“A simple, targeted travel history can help us put symptoms of infection in context and trigger more detailed history, appropriate testing, and rapid implementation of protective measures,” explained Perl and colleague Dr. Connie Price, a professor of medicine/infectious disease at the University of Colorado.

The clinical community’s experience in dealing with severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola point to how critical it can be to identify disease through travel history, Perl and Price noted. They cited a missed opportunity in a 2014 Ebola case.

“In Dallas, a patient presented to an emergency department in 2014 after returning from Liberia with low grade fever, abdominal pain, dizziness, nausea and headache,” the authors wrote. “The patient had Ebola. Because clinicians did not obtain the one potentially distinguishing clinical clue — a travel history — the well-being of both the patient and caregivers were compromised.”

In the face of the COVID-19 epidemic, health organizations and individual countries have attempted to control the spread of the virus via strategies such as travel and public gathering restrictions, school closures, and city quarantines, Perl and Price noted. But these measures may not be enough.

“Investigators estimated that there were almost 59,000 cases in Wuhan and 3,500 in other regions in China before the travel ban was implemented. … A recent report suggests that, because of the incubation period for COVID-19, the spectrum of symptoms, and the time during the incubation period persons may fly, 46% would be missed by airport-based screening,” they wrote. “Available data specific to COVID-19 suggest that screening and restricting travelers may have limited impact on containment.”

All members of the healthcare team need to integrate epidemiologic information such as travel history in their risk assessments in the same way they ask about tobacco exposure to assess cancer and heart disease risk, according to Perl and Price.

“They need a simple script to elicit clues for emerging infectious diseases and must be informed about current emerging pathogen threats, such as COVID-19,” the authors concluded. “Including travel history as a vital sign could serve as a warning sign that prompts protective measures.”

Stronger Than Average Threat,  Genetics Reveal 

The rise of next-generation sequencing has led to a boom of viral sequence discovery. The genus betacoronavirus is divided into four lineages (A-D) and contains a number of human viruses. Lineage B has around 200 published virus sequences and includes the severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 (previously called 2019-nCoV). It is still unknown if other viruses in this lineage have the potential to emerge in humans. Moreover, current techniques to study whether these viruses can enter human cells are technically demanding, time-consuming, and expensive.

Many viruses, including betacoronaviruses, use cell entry as a means of cross-species transmission. All coronaviruses encode a surface glycoprotein — a spike — that binds to the host-cell receptor and mediates viral entry. The host receptor for SARS-CoV-2 has been identified as angiotensin-converting enzyme 2 (ACE2). For betacoronaviruses, a single region on the spike called the receptor-binding domain (RBD) mediates this binding interaction. After binding, the host proteases cleave the spike, facilitating virus entry.

With underlying mechanisms in mind, and with the goal of overcoming testing limitations, Michael Letko, PhD, and colleagues from the NIH took a reductionist approach to studying coronavirus entry. They developed a scalable, biosafety level 2-compatible method for detecting the minimal region of coronavirus that’s essential for interacting with a host receptor.

Relying on the principle that RBDs on coronavirus spikes are capable of folding independent of the rest of the spike protein, and that they contain all of the information needed for host receptor binding, the NIH researchers tested receptor usage of all published unique RBD sequences for lineage B coronaviruses.

They found that lineage B RBDs divide into three functionally distinct clades. Only clade 1 RBDs contain all 14 residues that have been shown through crystallography to interact with human ACE2. Using synthetic biology and molecular engineering, combinations of coronaviruses were generated to test the specificity of RBDs, the importance of protease in viral entry, and whether these two processes are coupled.

The studies revealed that protease-mediated entry is receptor dependent, with ACE2 entry being lineage B clade 1 specific. However, when the spike was genetically modified in clade 2 and 3 viruses, viral entry was improved to varying degrees. This suggests that the limiting factor of viral transmission may be protease processing.

Interestingly, the RBD for SARS-CoV-2 has residues and motifs found in all three clades but uses ACE2. This may explain the human-to-human transmissibility of the virus. It contains most of the contact points with human ACE2 that are found in clade 1 and some amino acid variations that are unique to clades 2 and 3. The researchers suggest that it may be possible that SARS-CoV-2 arose from recombination between clade 1 and the other clades.

Overall, the results of the study emphasize the importance of continued surveillance of coronaviruses at the sequence and functional levels in order to better prepare for the next emerging virus.

Courtesy of LabPulse.com

March 3, 2020 — After an on-and-off courtship, Thermo Fisher Scientific announced it is set to acquire Qiagen in a deal worth $11.5 billion. The transaction will give Thermo Fisher access to Qiagen’s molecular diagnostics expertise and potentially lead to faster development of diagnostic tests.

The deal values Qiagen at 39 euros ($44) per share, which is 23% higher than its closing price on March 2.
In terms of IVD company rankings, Thermo Fisher is the fifth largest and Qiagen ranks No. 10, according to Kalorama estimates. The combined company would have $4 billion to $5 billion in IVD-related revenue.

Thermo Fisher said the deal will expand its specialty diagnostics portfolio by adding Qiagen’s capabilities in molecular diagnostics. Thermo Fisher’s strengths include next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR) technologies, while Qiagen markets molecular diagnostics for infectious diseases. In an investor briefing on March 3, Thermo Fisher explained how the companies’ offerings are complementary (see table).

“The combined company will accelerate the development of higher-specificity, faster and more comprehensive tests that may improve patient outcomes and reduce the cost of care,” Thermo Fisher said in a statement.

Qiagen products will benefit from Thermo Fisher’s commercial and geographic reach. In 2019, Qiagen reported revenue of $1.526 billion in 2019, up by 4% after currency adjustments from 2018. The company reported a loss for the year of $41.5 million, compared with net income of $190.4 million in 2018.

Complementary diagnostic products offered by Thermo Fisher, Qiagen
Thermo Fisher Qiagen Benefits of combination
  • Allergy and autoimmunity
  • Transplant diagnostics
  • QuantiFeron-TB Gold Plus latent tuberculosis detection test
  • Increased access to a more comprehensive specialty diagnostics portfolio
  • Genetic analysis technologies (including qPCR, NGS, Sanger, and microarrays)
  • Molecular diagnostics for infectious disease (QIAsymphony)
  • Syndromic testing capability (QIAstat)
  • Companion diagnostics offering
  • Bioinformatics capabilities
  • Higher-value diagnostic insights (accuracy, speed)
  • Improved healthcare economics

Source: Thermo Fisher investor presentation.

Thermo Fisher’s interest in acquiring Qiagen had been publicized in a Bloomberg report in November, boosting Qiagen’s value to $8.3 billion. At the time, Qiagen said it was considering offers from multiple suitors and reviewing what would make the most sense strategically. However, in January, Qiagen said the options were not compelling and that all discussions regarding an acquisition had been terminated.

The deal will affect several fields, such as lab instrumentation, next-generation sequencing, and pharmaceutical research.

Qiagen has made a number of acquisitions that expanded its position in molecular diagnostics, and it includes tests in just about every facet of molecular testing: automated DNA sample processing, molecular HPV testing, companion test development, liquid biopsy, NGS automation, and, last but not least, digital PCR, commented Bruce Carlson, publisher of Kalorama Information, a sister company of LabPulse.com.

Qiagen has several deals with pharmaceutical companies in place and creates greater opportunity in personalized medicine for Thermo Fisher. Qiagen is developing a pipeline of assays for preventive screening and diagnostic profiling of diseases and the detection of biomarkers to guide precision medicine in cancer and other conditions, Carlson commented.

In terms of IVD company rankings, Thermo Fisher is the fifth largest and Qiagen ranks No. 10, according to Kalorama estimates. The combined company would have $4 billion to $5 billion in IVD-related revenue. The top four — Roche, Abbott, Danaher, and Siemens — are very large, but the new entity would be competitive and could change positions, Carlson said.

The deal is expected to close in the first half of next year.