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As the COVID-19 crisis surfaced in the United States, molecular diagnostic manufacturers went to work with new RT-PCR testing kits. The worldwide demand for COVID tests has materialized rapidly from zero and already on course become a 1.3 billion-dollar market in the first half of 2020.  There have been hundreds of tests on the market receiving EUAs from the Food and Drug Administration, but a survey from the Association of Molecular Pathology demonstrated that only a few are used by laboratories.  As part of a survey for the Association for Molecular Pathololgy (AMP) : https://www.amp.org/advocacy/sars-cov-2-survey/  labs were asked their top ten testing methods. Among them: Abbott m2000, Roche cobas were the top two vendors in most labs’ top tens.

This makes sense, these systems are the ones in most laboratories and the ones that are set up for other RT-PCR uses such as testing for HIV. Other tests in labs’ Top Tens included: Cepheid Gene Xpert Roche cobas, Hologic Panther, DiaSorin Simplexa, Quidel Lyra, Thermo Fisher Taq Path, Abbott IDNOW, CDC Test. There’s still a market for innovators.  (Labs also were in many cases citing their own LDTs as top test).

There is debate regarding how early the first cases appeared in various parts of the world, but in the first quarter there were only a small number of countries with sufficient cases to prompt serious actions.

Kalorama’s report updates with detail on both COVID-19 molecular testing markets and non-COVID-19 testing: https://kaloramainformation.com/product/molecular-diagnostics-markets-in-the-covid-19-era/

Kalorama estimates a 4.5 billion dollar market for COVID-19 testing by year’s end. Unique near-patient tests, sample collection methods such as saliva or self-test, NGS and mass spectrometry testing, multiple PCR test targets, improved antibody tests, high throughputs, extraction kit workarounds – these are all examples of areas that innovators can improve. The worldwide demand for COVID tests has materialized rapidly from zero and is on course to become a multi-billion dollar market in 2020.

In different regions, there are different situations with respect to COVID-19 testing:

US: The United States has been the largest market in terms of both tests and revenues. In the US, testing has followed a fairly consistent, linear trajectory as the new cases plateaued, then declined, then rose again. This is not entirely unique, but represents a sort of “middle” situation where the curve was greatly diminished but was not completely squashed. The overall pattern actually represents the combination of multiple regions – the Northeast, the focus of the initial spike, is now seeing new cases reduced to close to 90% of the peak, while areas of the South are rising rapidly and some other regions are relatively flat.

Europe: Western Europe experienced a large surge in cases just after the initial spike in Asia. Like Asia, many of the Western European countries were also mostly successful in squashing the curve to a manageable level. With some exceptions, the number of new daily cases is well under 90% of its volume at the peak. To provide one example, Italy has seen its new cases drop to almost none while its testing volume remains flat.

Asia: While many Asian countries such as Japan and South Korea were mostly successful in eliminating the virus, there is now a surge in several high population countries including India, Bangladesh, and Pakistan. In these South Asian countries, the initial spike arrived a few months later and is still running its course. Testing resources are much more scarce, causing some labs to resort to serology testing for diagnostic purposes.

Latin America: While Latin America and ROW are experiencing high growth right now, significantly increasing their shares, the impact on this market is diminished due to lower per capita testing; in addition, the revenues are significantly affected by lower prices. Europe’s share is anticipated to drop off gradually due to many countries appearing to contain the virus; however, Eastern Europe is still experiencing a surge.

The news is not all positive from a revenue perspective.  Molecular testing on COVID is paired with declines in more traditional molecular tests as patients avoided doctors and continue to reduce in person doctor visits during lockdown.  Down but not out segments include cancer, histology and inherited diseases which are expected to continue to grow, perhaps surge, later in the year and into 2021. Prior to COVID-19, liquid biopsy was one of the stars of this segment. Favorable regulatory policies in the United States and promising studies will enhance companion testing. New LDT tests in Inherited disease testing in particular, using IVD supplies which includes non-invasive prenatal testing (NIPT), is driven by the demand in China. Even though the demand is for laboratory test services and not for IVD products, the demand for instruments, kits and consumables that are approved by regulatory agencies is driving the segment. However, the market opportunities may be challenging to access by foreign IVD companies due to the regulations promoting domestic companies.

Kalorama’s report updates with detail on both COVID-19 molecular testing markets and non-COVID-19 testing: https://kaloramainformation.com/product/molecular-diagnostics-markets-in-the-covid-19-era/

Lab-developed tests were controversial before the COVID-19 pandemic, and there was attempts at regulating them more in the United States.  Then came a massive infectious disease threat for which lab developed tests were essential.  The sudden onset of a disease for which there were no existing test products, so labs had to develop their own.

Lab-developed tests are likely to be a fifth of tests, according to a recent survey by the Association for Molecular Pathology.

There has been a running stalemate under the role of laboratory-developed tests, which may or may not change in the wake of COVID-19.  Originally, LDTs were designed to be solutions that do not otherwise exist yet on the market. Hence, FDA has not enforced premarket reviews of LDTs. Instead , LDTs are regulated by the Centers for Medicare and Medicaid Services (CMS), where they are categorized as high- complexity tests under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). However, technology advancements have facilitated designing of complex LDTs, with some being similar to IVD tests that have undergone FDA review before entering the market.

The majority of LDTs are based on molecular diagnostic technologies such as nucleic acid amplification, array-based hybridization, NGS, and liquid biopsies.

Could COVID-19 break the stalemate towards the side of test innovation and LDT?  Lab Developed Tests were critical for the crisis in late march. For instance there were media reports  January that SARS-CoV-2 virus had reached the US, lab professionals said they were hesitant to launch LDTs. They were unsure if the agency would practice “enforcement discretion.”

One showdown proved ill-timed for the side of stricter FDA regulation of tests.   In March 2020, lawmakers introduced a bill that would vastly change the oversight system for diagnostics in this country and give the US Food and Drug Administration explicit authority to regulate tests developed by labs, legislators and media were confused by what seemed to be a reversal of need for more testing.    The bipartisan (VALID) Act was designed to streamline regulations and speed access to tests in public health emergencies like the present COVID-19 pandemic.

  Opponents argued that in the hands of the FDA, the lab industry would be overburdened with regulation and no longer nimble in the face of advancing science or a sudden public health crisis.

Kalorama Information produces 30 reports a year.  Their reports can be found at www.kaloramainformation.com

The landscape of COVID-19 testing has been rapidly evolving.  New products and services are continually being introduced, and regulatory approvals have been growing and expanding to include more types of tests, samples, and sample collection methods.  With the sudden global demand and governments loosening requirements during the crisis, there has been an unprecedented flood of products.  It has attracted scores of companies, some of which have rushed or cut corners and produced tests with low accuracy.  In many cases there have been recalls and the FDA has issued warning letters, revoked EUAs, and tightened some of its more lenient regulations, for example for Policy D antibody tests.

Along with labs procuring additional systems and increasing their staffing, there are other ongoing activities that are being undertaken to address the various challenges of COVID-19 testing.  The growth is expected to continue, even with some areas seeing declining cases for example in the US.  Most labs are using multiple suppliers’ COVID tests, as a way to hedge against shortages or other problems.

A significant but decreasing portion of countries still remains relatively unscathed with small numbers of cases.  There are only about 40 countries with zero to one case per day, out of 210, mainly islands or less-travelled areas.  Regions that are seeing their first spike in cases are now facing the issue of scaling up to the necessary volume.  Due to the unknowns that remain about the virus, it is also still a challenge to determine the appropriate level of testing.  Some lessons can be applied from the countries that were hit earlier

This is partly dictated by the existing instrumentation but there is usually some flexibility.  Pooling and other techniques are being incorporated to stretch supplies out for more tests.

Due to the supply situation as well as the nature of scientific collaboration, many professional organizations have taken the initiative to address the challenges.  The Association for Molecular Pathology (AMP), for example, has developed five key recommendations for testing labs to best respond to the pandemic, based on its recent survey –

 

  • Reassess type and location of SARS-CoV-2 testing services needed – better match to the situation
  • Reprioritize supply allocations based on clinical testing needs, which could change over time – e.g. as prevalence falls or climbs
  • Increase transparency, communication, and real-time transmission of information between laboratories and suppliers (commercial manufacturers and government) – reagent, supply, resource availability and supply quantities, allocation strategies etc
  • Real-time coordination amongst laboratories to leverage moments of excess capacity – share supplies to ensure rapid processing of samples
  • Standardize agency reporting format and processes for reportable infectious diseases during a pandemic – reduce significant burden on labs, reduce delays, establish electronic systems and formats.


For countries that are still at the beginning of the crisis, taking these steps could improve the chances of success; and for the others, they will likely be among the key considerations to prepare for the next pandemic.

Companion diagnostics are rising to the forefront of pharmaceutical development and treatment. Companion diagnostics increase the probability of clinical success by identifying patients with the presence of biomarkers or disease-specific therapeutic targets that can dramatically improve outcomes. The COVID-19 pandemic has gripped the world and continues to be a major area of research and development for diagnostic test developers.

Several approaches continue to evolve, including the use of personalized medicine technologies being adjusted to address the COVID-19 need.

Spartan Bioscience developed its CE and FDA approved DNA analyzer to detect risk of poor treatment choices for patients taking various antiplatelets, antidepressants and PPIs.  People carrying CYP2C19 mutations can impair drug metabolism and alter response to drug therapy.  Over the first-half of 2020, Spartan Bioscience has shifted its technology to focus on detecting COVID-19 and Legionella using its qPCR on-site DNA analyzer.

Our report on companion diagnostics (https://kaloramainformation.com/product/companion-diagnostics-in-the-covid-19-era/), and found that COVID-19 has had a small impact on the market for important cancer test and drug combinations.  But since the oncology therapeutics these tests help facilitate are critically important for patients, that impact was limited.  This was according to informal surveys of companion diagnostic vendors conducted by the authoring analysts of the market report.

Along with new developments, diagnostic service providers are also shifting workloads to address the demand for COVID-19 services.  MiraDx, for example, has opened its CLIA-certified lab to providing COVID-19 test services.  The lab has an analyze capacity of over 9,000 tests with no backlog, reported by MiraDx.  The company also reports test results are available in approximately 48 hours and are being prioritized for hospitals, essential workers and field-based healthcare workers.  MiraDx lists the test at $150 per completed test.
Minimal Ongoing Disruptions

Analysts contacted some oncology treatment centers and others focusing on CDx activity to determine the impact of COVID-19 on laboratory activity.  The analysts of the report found.

• Initial (March 2020) decline in CDx requisitions, yet by April 2020 this was largely resolved;
• Less than 10 percent reduction in test volume reported;
• Budgets largely frozen, no capital expenditures will be initiated in the foreseeable future;
• Some backlog on processing tests due to restructuring of hours and laboratory layout requirements; and
• By appointment only lab draws were in effect beginning around February 2020 for some facilities and ongoing through April 2020 which impacted test volume slightly.

Delaying treatment in patients with overall good prognosis would be detrimental to the outcome in some patients prescribed targeted therapies, primarily cancer therapies.  Therefore, oncologists report only minimal delays in treatment which is often determined case-by-case, dependent on factors such as disease status, cancer type, age of the patients, etc.

For example, systemic therapy may be delayed for a short period in patients aged 50 or older with non-aggressive tumor types; in contrast, delaying treatment in an aggressive tumor could be catastrophic to the patient’s outcome.  The National Institutes of Health (NIH) lists more than 200 clinical trials currently underway for COVID-19 biomarker discovery, development and clinical application.

Along with new developments, diagnostic service providers are also shifting workloads to address the demand for COVID-19 services.  MiraDx, for example, has opened its CLIA-certified lab to providing COVID-19 test services.  The lab has an analyze capacity of over 9,000 tests with no backlog, reported by MiraDx.  The company also reports test results are available in approximately 48 hours and are being prioritized for hospitals, essential workers and field-based healthcare workers.  MiraDx lists the test at $150 per completed test.

There is also a growing trend for treatment centers, specifically cancer treatment centers, and research hospitals to get involved in the COVID-19 recovery plan.  The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University (Baltimore, Maryland, United States) is gearing up to commence a Phase II trial to promote recovery from COVID-19 with ivermectin or bicalutamide endocrine therapy.  The study is an interventional trial with an estimated enrollment of 60 participants that have had a confirmed PCR test of COVID-19 infection and require inpatient hospitalization due to COVID-19 with minimal or no respiratory symptoms. Estimated start date is June 2020 with estimated completion in June 2021.

 

Kalorama’s new study on hematology and coagulation finds increased uses of coagulation testing  to determine COVID-19’s unfortunate effects on the blood health of patients.

Coagulation is a complex process in which multiple enzymes and proteins regulate blood flow and clot formation. Coagulation (clot formation), fibrinolysis and platelet aggregation are a part of this process. Fibrinolysis refers to the breakup of blood clots. It is a normal body process that keeps naturally occurring blood clots from growing and causing problems. Anticoagulant drugs help prevent blood platelets from sticking or clumping together, reducing the likelihood that arteries will be blocked by a clot, leading to a stroke or heart attack.

The most widely used drug is Coumadin (Warfarin) that is prescribed for patients with atrial fibrillation, artificial valves and phlebitis. People on warfarin need to have their blood monitored regularly (sometimes weekly and sometimes monthly) to ensure that they are taking the right dosage to avoid clotting if the dosage is too low and also unintentional bleeding when the dosage is too high. This is done with a blood clotting test known as the International Normalized Ratio (INR, formerly known as the
Prothrombin Time test). Proponents of self-testing claim that daily or weekly testing at home helps patients maintain better anticoagulant activity – not too much and not too little.

There are newer oral anticoagulants on the market, such as rivaroxaban (Xarelto), apixaban (Eliquis) and dabigatran (Pradaxa). They are at least as safe and effective as warfarin, and they do not require regular coagulation monitoring with a PT/INR. However, hematologists will use immunoassays to measure the amount of drug concentration in a patient’s blood to assure that the amount of drug is in the therapeutic range. This is akin to therapeutic drug monitoring by immunoassay of antibiotics (gentamicin), antiepileptics (such as carbamazepine, phenytoin and valproic acid), and antipsychotics (such as pimozide and clozapine).

Patients with atrial fibrillation and artificial valves are beginning to switch from warfarin to next-generation drugs. Pharmaceutical companies have heavily invested in direct-to-consumer advertising efforts, ultimately extolling the benefits of these drugs. At this time, this provides another test opportunity in coagulation testing. Several companies have already commercialized tests for the monitoring of the new anticoagulant drugs.

Coagulation testing, including d-dimer, is considered to be a growing indicator in the impact and clinical outcomes of patients with COVID-19. Screening with coagulation panels, including d-dimer, prothrombin time, platelet counts, and fibrinogen, is considered to be essential to identifying patients with severe COVID-19 risk and potential negative outcomes. Several international organizations are leading the charge in identifying and publishing recommendations and guidances for coagulopathy management in COVID-19 patients. Organizations endorsing increasing monitoring for patients with thrombotic diseases and implementing early interventions include:

• American College of Cardiology
• British Society of Hematology
• European Society of Vascular Medicine
• International Society of Thrombosis and Haemostasis
• North American Thrombosis Forum

FOR MORE INFORMATION:

Kalorama Information’s Hematology Markets

Drug discovery is a high-cost, risky business because only a fraction of the therapeutic targets selected for study will actually yield products that achieve regulatory approval by the U.S. Food & Drug Administration (FDA) or other global regulatory agencies. The average drug can take 10+ years to progress from the discovery phase to the clinic, with only one compound out of 10,000 evolving into a viable product. The increasing demand for outsourcing has spawned a proliferation of companies offering contract drug discovery services. Contractors competing in this sector range from small regional companies with a limited geographic reach to medium and large CROs with a large global footprint. As more pharmaceutical companies from emerging countries become major players in the pharmaceutical industry, and multinational pharmaceutical companies expand into emerging countries, the global demand for drug discovery services will continue to expand, although it will be affected by the 2020 corona virus pandemic, lockdown and expected recession.

According to Kalorama Information’s latest report, the market for outsourced drug discovery services has been robust. This is expected to change dramatically in 2020, with ongoing recovery through the five-year forecast period of this report. The global market is estimated at $31.6 billion in 2019 up 15.8% from $27.3 billion in 2018,

The net impact of the corona virus and lockdown will be to inhibit global drug discovery outsourcing while creating opportunities for the development of corona-related vaccines and therapies.

As of May 2020, economic analysts around the world broadly predict an economic recession resulting from the dramatic slowdown in business activities during the corona virus lockdown. The full impact of the global corona virus contagion is not yet understood. In fact, even as a clearer picture emerges in the coming months, the economic ramifications are unlikely to be fully grasped until 2021 or beyond.

As the lockdown requirements are designed to prevent the spread of the corona virus in large groups of individuals who have direct physical contact with each other, manufacturing operations of many companies have been suspended. The pharmaceutical and biotechnology industries, however, are considered life sustaining and therefore medicines and vaccines continue to be produced. As of early May 2020, no significant shortages have been reported.

This could change, however, if the lockdown requirements become more stringent; while the current trend appears to be easing of lockdown restrictions, a significant subsequent wave of infection could reverse this. Furthermore, the industry remains subject to market forces, economic cycles and consumer demand. Although low cost generic medications will probably maintain their sales levels, branded medicines are likely to suffer.

The FDA approved BioFire FilmArray COVID-19 test, as well as Mesa Biotech’s Accula.  Both can bring a COVID-19 diagnosis to the point of care where testing is most needed.   BioFire’s Film Array has thousands of placements.  Accula is a hand-held test.

https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations

Tests approved with an EUA include:

  • Mesa Biotech Inc. Accula SARS-Cov-2 Test
  • BioFire Defense, LLC BioFire COVID-19 Test
  • Cepheid Xpert Xpress SARS-CoV-2 test
  • GenMark ePlex SARS-CoV-2 Test
  • DiaSorin Molecular LLC Simplexa COVID-19 Direct assay
  • Abbott Molecular Abbott RealTime SARS-CoV-2 assay
  • Quest Diagnostics Infectious Disease, Inc. Quest SARS-CoV-2 rRT-PCR
  • Quidel Corporation Lyra SARS-CoV-2 Assay
  • Laboratory Corporation of America (LabCorp) COVID-19 RT-PCR Test
  • Primerdesign Primerdesign Ltd COVID-19 genesig Real-Time PCR assay
  • Hologic, Inc. Panther Fusion SARS-CoV-2
  • Thermo Fisher Scientific, Inc. TaqPath COVID-19 Combo Kit
  • Roche Molecular Systems, Inc. (RMS) cobas SARS-CoV-2

 

 

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.

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