Saturday, February 8, 2025
Home Blog Page 130

Novartis to study hydroxychloroquine for Covid-19

0

April 20, 2020: Novartis has entered an agreement with the US FDA to conduct a Phase III clinical trial of hydroxychloroquine to treat hospitalised patients with Covid-19. Hydroxychloroquine, which is commonly used to treat malaria and some autoimmune diseases, showed anti-SARS-CoV-2 activity in laboratory tests.

Sponsored by Novartis, the new Phase III trial will assess hydroxychloroquine as a potential Covid-19 therapy in around 440 participants. The company’s subsidiary, Sandoz, will supply the drug for the study, which will be performed at more than 12 sites in the US. Novartis intends to start patient recruitment in the coming weeks.

Novartis Global Drug Development head and chief medical officer John Tsai said: “We recognise the importance of answering the scientific question of whether hydroxychloroquine will be beneficial for patients with Covid-19 disease.

“We mobilised quickly to address this question in a randomised, double-blind, placebo-controlled study.”

Trial participants will be randomised to receive hydroxychloroquine, hydroxychloroquine plus azithromycin or placebo. All treatment arms will involve standard of care for Covid-19.
Previously, Novartis, through Sandoz, announced plans to donate up to 130 million hydroxychloroquine tablets to meet the needs related to global clinical research in the event the drug is found to be promising in Covid-19 treatment.

Sandoz has so far donated 30 million tablets to the US Department of Health and Human Services and will send additional shipments to other countries based on requests. In addition, Novartis plans to provide any intellectual property, within its control, of hydroxychloroquine for Covid-19 via non-exclusive voluntary licences, waivers or similar methods.

Novartis also established a clinical investigation team to enable rapid access to approved clinical requests and clinical evaluation support for its medicines to be repurposed for Covid-19. Apart from hydroxychloroquine, Novartis plans to sponsor or co-sponsor trials of ruxolitinib and canakinumab for hospitalised Covid-19 patients.

Requests for investigator-launched trials of ruxolitinib, canakinumab, imatinib mesylate, secukinumab, hydroxychloroquine and valsartan in Covid-19 indications have been granted.
https://www.clinicaltrialsarena.com/news/novartis-hydroxychloroquine-covid-trial/

New research to assess extent of coronavirus infection in children and teenagers

0

April 20, 2020: “New research funded by the NIHR and UK Research and Innovation (UKRI) will assess rates of coronavirus infection and immunity in children and teenagers across the UK, to provide vital evidence to guide the response to the pandemic.

Understanding the prevalence of SARS-CoV-2 infections in the community is important for the public health response to the COVID-19 pandemic. This is particularly key for children and teenagers, who are mostly spared the worst of the disease but could be spreading the virus to others.

The What’s the STORY (Serum Testing of Representative Youngsters) study at University of Oxford will collect blood samples from children and teenagers aged 0-19 years with symptomatic and asymptomatic coronavirus infection and measure levels of antibodies, a marker of having had the disease and now having immunity.

The researchers, led by Professor Matthew Snape, will identify the proportion of children and teenagers who had symptoms of COVID-19 and what proportion are likely to have immunity against the virus. It will also determine how many children have not yet been infected and may remain susceptible when lockdown measures are relaxed.

These data can then be used in mathematical models of the circulation of SARS-CoV-2 and the expected severity and duration of the current outbreak. The multi-site What’s the STORY project is an ongoing research study led by Oxford Vaccine Group, in collaboration with Public Health England and a network of clinical sites in Bradford, Bristol, Leeds, Manchester, Sheffield, Southampton and London.

The project was set up in 2019 as a pilot surveillance programme to review a new method of monitoring how well the UK immunisation programme is working. The research has now been adapted to track an additional 1200 children and teenagers for the duration of the COVID-19 outbreak.

Professor Matthew Snape said: “One of the many unknown with the current coronavirus outbreak is how many children are being infected and potentially passing on infection to others. Understanding this is vital to understanding how to manage the outbreak response, including decisions about when to re-open schools.

“With this study, the Oxford Vaccine Group are working with Public Health England and a network of sites across England to systematically study how many children and teenagers have immunity against this virus, which in turn tells us how many have had the infection and how many remain potentially vulnerable.”

This project is one of 21 new studies into COVID-19 that have been funded by the NIHR and UK Research and Innovation (UKRI). The two funding rounds to date have invested £24.6 million into 26 research projects to respond to the coronavirus pandemic.”
https://www.nihr.ac.uk/news/new-research-to-assess-extent-of-coronavirus-infection-in-children-and-teenagers/24653

Oxford project receives funding to assess novel coronavirus infection rates in children and teenagers across the UK.

0

April 20, 2020: “A multi-site project, called ‘What’s the STORY?’ has received funding from UK Research and Innovation (UKRI) to assess no vel coronavirus infection rates in children and teenagers across the UK. Given the importance of this study to the national Covid-19 response, it has been deemed a priority study for the National Institute for Health Research’s (NIHR) Urgent Public Health Response.

The team, led by Professor Matthew Snape from the Oxford Vaccine Group at the University of Oxford, aims to determine how many children and teenagers have been infected with Covid-19, and what proportion of those have had symptoms. The research will also determine how many children and teenagers have not yet been infected and may remain susceptible to Covid-19 when lockdown measures are relaxed. 

Professor Matthew Snape, Chief Investigator on the study, said: “To understand the current coronavirus pandemic, we need to work out how many people are becoming infected without showing any symptoms.”

‘What’s the STORY?’ was set up in 2019 as a pilot study to evaluate the UK immunisation programme, but it has now been adapted in response to the Covid-19 pandemic.

This new funding allows the project to expand to include new study sites and recruit an additional 1200 children and teenagers (aged 0-19 years) from across England. The team will also test samples already collected and these data, along with medical histories of Covid-19 symptoms, will provide valuable information into the levels of virus circulating in this segment of the population.

Professor Snape continues:“With this study we will systematically study the proportion of children and teenagers with immunity against this virus during the course of the pandemic.”

Understanding the prevalence of Covid-19 in the community is vital to supporting public health in response to the pandemic, including in children and teenagers, who are mostly spared the worst of the disease but could be spreading the disease to others. 

Professor Snape concludes:“This information is vital to informing public policy about how to best manage this devastating outbreak.”

‘What’s the STORY?’ is an ongoing research study led by Oxford Vaccine Group in collaboration with Public Health England (PHE) and a network of clinical sites in Bradford, Bristol, Leeds, Manchester, Sheffield, Southampton and St George’s, London.

A key aspect of this project is the need to assess a representative cohort of children and young people, in order to give an accurate “snapshot” of the wider population. The study team are keen to engage a range of individuals and must ensure that the group tested is not biased towards people who think they may have been infected with Covid-19, and for this reason, the study team will not provide test results to participants. 

Existing sites are primarily recruiting through mail out by invitation letters to selected postcodes, and eligible individuals from the catchment areas of each study site have been or will soon be contacted with information about the project. However broader recruitment to new sites is expected to open within the next few weeks, and updates will be available on the study website: whatsthestory.web.ox.ac.uk.”

https://www.research.ox.ac.uk/Article/2020-04-20-oxford-project-receives-funding-to-assess-novel-coronavirus-infection-rates-in-children-and-teenagers-across-the-uk

NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options

0

April 17, 2020: “The National Institutes of Health and the Foundation for the NIH (FNIH) are bringing together more than a dozen leading biopharmaceutical companies, the Health and Human Services Office of the Assistant Secretary for Preparedness and Response, the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration and the European Medicines Agency to develop an international strategy for a coordinated research response to the COVID-19 pandemic.

The planned Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) partnership will develop a collaborative framework for prioritizing vaccine and drug candidates, streamlining clinical trials, coordinating regulatory processes and/or leveraging assets among all partners to rapidly respond to the COVID-19 and future pandemics. This is part of the whole-of-government, whole-of-America response the Administration has led to beat COVID-19.

“We need to bring the full power of the biomedical research enterprise to bear on this crisis,” said NIH Director Francis S. Collins, M.D., Ph.D. “Now is the time to come together with unassailable objectivity to swiftly advance the development of the most promising vaccine and therapeutic candidates that can help end the COVID-19 global pandemic.”

Coordinated by the FNIH, ACTIV government and industry partners will provide infrastructure, subject matter expertise and/or funding (both new and in-kind) to identify, prioritize and facilitate the entry of some of the most promising candidates into clinical trials. Industry partners also will make available certain prioritized compounds, some of which have already cleared various phases of development, and associated data to support research related to COVID-19.  The partnership is being developed with input from a steering committee managed by the FNIH which includes leaders from NIH, FDA and the research and development organizations of the companies.

“COVID-19 is the most significant global health challenge of our lifetime, and it will take all of us working together as a global community to put an end to this pandemic,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson. “We will need to harness the best ideas from multiple stakeholders, including governments, regulatory authorities, academia, NGOs and industry to stop COVID-19. At Johnson & Johnson, we are committed to working closely with FNIH, IMI and are part of other important consortia to speed solutions to stop this pandemic.”

“Battling the COVID-19 pandemic is far too great a challenge for any one company or institution to solve alone,” said Mikael Dolsten, M.D., Ph.D., Chief Scientific Officer and President, Worldwide Research, Development and Medical, Pfizer. “We are seeing an unprecedented level of collaboration across the innovation ecosystem to address this global health crisis, and this potentially powerful NIH initiative may allow us to further accelerate the delivery of much needed therapies to patients around the world.” 

The research community is currently striving to sift through more than 100 potential preventives and therapeutics for COVID-19. ACTIV will aim to provide guidance which can be used to prioritize the plethora of vaccine and therapeutic candidates in development and connect clinical trial networks to test new and repurposed candidates quickly and efficiently.

“Using the most advanced clinical trial methods to rapidly test multiple interventions will help get the answers we need as soon as possible to expedite potential prevention and treatment approaches to fight COVID-19,” said FDA Commissioner Stephen M. Hahn, M.D. “Collaboration is a critical ingredient for success and the FDA will continue to use every tool possible under our Coronavirus Treatment Acceleration Program(link is external) to speed the development of safe and effective medical countermeasures.”

ACTIV will have four fast-track focus areas, each of which will be led by a highly motivated working group of senior scientists representing government, industry and academia:

  • Standardize and share preclinical evaluation methods in an open forum that allows for comparison and validation by:
  • Establishing a centralized process and repository for harmonizing and sharing methods and evaluating models
  • Extending access to high-throughput screening facilities, especially in biosafety level-3 laboratories, with a goal of testing all compounds that have been in human clinical trials to identify the potential to apply these compounds to COVID-19
  • Increasing access to validated animal models
  • Enhancing comparison of approaches to identify informative assays

Prioritize and accelerate clinical evaluation of therapeutic candidates with near-term potential by:

  • Establishing a steering committee with relevant expertise and objectivity to set criteria for and rank potential candidates submitted by industry partners for first wave and subsequent evaluation
  • Developing a complete inventory of potential candidates with different mechanisms of action and acceptable safety profiles
  • Designing, launching and openly sharing master protocols with agreed upon endpoints, sampling and analysis for evaluating candidates
  • Using a single control arm to enhance trial efficiency
  • Maximize clinical trial capacity and effectiveness by:
  • Connecting existing networks of clinical trials to build capacity and capabilities, including specialization in different populations and disease stages
  • Leveraging infrastructure and expertise from across NIH networks, including:
  • Adjuvant Discovery and Adjuvant Development Programs
  • AIDS Clinical Trials Network
  • Clinical and Translational Science Awards Program
  • Clinical Trials in Organ Transplantation
  • Cooperative Centers on Human Immunology
  • HIV Prevention Trials Network
  • HIV Vaccine Trials Network
  • Human Immunology Project Consortium
  • International Network for Strategic Initiatives for Global HIV Trials (INSIGHT) Network
  • National Cancer Institute Community Oncology Research Program
  • National Cancer Institute’s National Clinical Trial Network
  • Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network
  • Strategies to Innovate EmeRgENcy Care Clinical Trials Network (SIREN)
  • T and B Cell Discovery Programs and Immune Epitope Database
  • Vaccine Treatment and Evaluation Units
  • Establishing a coordination mechanism across networks to expedite trials, track incidence across sites and project future capacity
  • Advance vaccine development by:
  • Creating a collaborative framework to share insights into natural immunity and vaccine candidate-induced immune response by:
  • Mapping epitopes and developing assays
  • Establishing protocols for sampling and immunological analyses and reagents
  • Collecting clinical data on immunological responses and endpoints, to enable meta-analysis of correlates of protection
  • Engaging with regulators on surrogate endpoints for clinical evaluation”

“This powerful public-private partnership will focus and expedite R&D activities required to combat COVID-19,” says Maria C. Freire, Ph.D., President and Executive Director, FNIH. “Working in lock-step, the public and private sectors will maximize the chances of success and provide a roadmap to pre-emptively manage future threats.”

https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options

Coronavirus treatment: Vaccines and drugs in the pipeline for COVID-19

2

As of April-2020, There are 5 vaccine candidates and 21 drug candidates are under the clinical stage of development

There are more than 70 drug candidate under pre-clinical stage of development

Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus which is named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV).

  • It was first identified amid an outbreak of respiratory illness cases in Wuhan City, Hubei Province, China.
  • The WHO declared the COVID-19 outbreak a global health emergency on On January 30, 2020. On March 11, 2020, It was declared as a global pandemic by WHO
  • It is noted that its first such designation since declaring H1N1 influenza a pandemic in 2009.

There is no drug, biologicals, vaccines approved for the treatment of COVID19. The following categories of drugs are under development:

  • Antiviral
  • Anti Inflammatory
  • Plasma therapy
  • Vaccines

Kaletra:

  • It was tested by AbbVie’s for COVID19. It is a combination of lopinavir and ritonavir. Lopinavir is an inhibitor of the HIV protease.
  • Ritonavir inhibits the CYP3A-mediated metabolism of lopinavir, thereby providing increased plasma levels of lopinavir.
  • Kaletra failed across the board in a 199-patient clinical trial. It didn’t a top standard of care at improving clinical symptoms, extending lifespan or cutting viral shedding in patients hospitalized with severe COVID-19, results from a study published Wednesday in The New England Journal of Medicine show”

    https://clinicaltrials.gov/ct2/show/NCT00234923

(Ganovo + Ritonavir):

  •  It is being evaluated by Ascletis. Danoprevir (Ganovo) is an NS3/4A protease inhibitor. This open, controlled Phase IV trial will evaluate the efficacy and safety of Danoprevir sodium tablet in hospitalized patients infected with SARS-CoV-2.
  • The HCV NS3/4A protease involves in viral replication and suppressive effects on host response to viral infection.
  • Ritonavir inhibits the HIV viral proteinase enzyme that normally cleaves the structural and replicative proteins that arise from major HIV genes, such as gag and pol

Study TitleEfficacy and Safety of Ganovo (Danoprevir) Combined With Ritonavir in the Treatment of SARS-CoV-2 Infection.

https://clinicaltrials.gov/ct2/show/NCT04345276?intr=Danoprevir&spons=ascletis&phase=3&draw=2&rank=1

Actemra:

  • It is a brand name for Tocilizumab. It is being tested by Roche for COVID19

    Mechanism of action:
  • “Tocilizumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signalling through these receptors.
  • IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes and fibroblasts.
  • IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute-phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation.
  • IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis.”

As of 19th Mar-2020, Roche announced that “we are working with the Food & Drug Administration (FDA) to initiate a randomised, double-blind, placebo-controlled Phase III clinical trial in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), a part of the US Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR), to evaluate the safety and efficacy of Actemra®/RoActemra® (tocilizumab) plus standard of care in hospitalised adult patients with severe COVID-19 pneumonia compared to placebo plus standard of care”
https://www.roche.com/media/releases/med-cor-2020-03-19.htm

Lenzilumab:

 It is being tested by Humanigen for COVID19. FDA Approved initiation of Humanigen’s Phase III Study of Lenzilumab in COVID-19 Patients.

It is multi-center, randomized, placebo-controlled, double-blinded Phase III study enrollment to focus on adult, hospitalized patients with COVID-19 pneumonia and at high risk of progression to respiratory failure.
https://clinicaltrials.gov/ct2/show/NCT04351152?intr=Lenzilumab&draw=2&rank=2

Mechanism of action:
“A recombinant monoclonal antibody against the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), with potential immunomodulating activity. Upon administration, lenzilumab binds to and neutralizes GM-CSF.

This prevents GM-CSF binding to the GM-CSF receptor, which is a heterodimeric protein expressed on myeloid progenitor cells, and prevents GM-CSF-mediated signaling.

This may induce apoptosis in and inhibit proliferation of cancer cells that overproduce GM-CSF. GM-CSF plays a key role in the differentiation and proliferation of monocytes, macrophages and granulocytes; elevated levels of GM-CSF are associated with certain autoimmune diseases, inflammatory diseases, and cancers”

https://www.cancer.gov/publications/dictionaries/cancer-drug/def/lenzilumab

CD24Fc:

  • It is being tested by Oncoimmune for COVID19
    Mechanism of action: 
    “CD24Fc has a dual mechanism of action:
  • First, CD24Fc binds DAMPs, trapping the inflammatory stimuli to prevent their interaction with TLR receptors
  • Second, CD24Fc binds Siglec G/10 and regulates host response to tissue injuries Siglec G/10-associated SHP1 inhibitory signalling
  • Both mechanisms likely act in concert to modulate immune responses.” http://www.oncoimmune.com/product-development/

Registered study: Phase III study registered with USFDA.

Study objective:
“The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe COVID 19.”
https://clinicaltrials.gov/ct2/show/NCT04317040?intr=CD24Fc&draw=2&rank=2

Prezcobix:

Shanghai Public health clinical centre is developing this drug for COVID19.
PREZCOBIX is a fixed-dose combination product containing 800 mg of darunavir and 150 mg of cobicistat.

“Darunavir, a HIV protease inhibitor, prevents HIV replication through binding to the enzyme, stopping the dimerization and the catalytic activity of HIV-1 protease. In particular, it inhibits the cleavage of HIV encoded Gag-Pol proteins.

  • Mechanism of Action:
  • cobicistat acts as a pharmacokinetic enhancer by inhibiting cytochrome P450 3A isoforms (CYP3A) and therefore increases the systemic exposure of coadministered agents that are metabolized by CYP3A enzymes”
  • It is an interventional randomized Phase III study to evaluate the efficacy and safety of Darunavir and Cobicistat for Treatment of COVID-19 (DC-COVID-19) https://clinicaltrials.gov/ct2/show/NCT04252274

Colchicine: 

On 8-April-2020, it was announced that “The Montreal Heart Institute (MHI) Research Centre has collaborated with New York City’s NYU Grossman School of Medicine for a new COVID-19 clinical study.

The clinical study, dubbed COLCORONA, will assess whether colchicine will serve as an effective treatment to prevent the phenomenon of major inflammatory storm present in adults suffering from severe complications related to COVID-19.”

  • COLCORONA trial will enrol around 6,000 participants who will be followed for 30 days and initial results will be revealed a few days upon the completion of a study.”

    Study Description:
  • This is a phase 3, multi-center, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of colchicine in adult patients diagnosed with COVID-19 infection and have at least one high-risk criterion.

Kevzara:

It is a brand name of sarilumab. Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus which is named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; formerly called 2019-nCoV). Kevzara: It is a brand name of sarilumab.

Kevzara was jointly developed by Sanofi and Regeneron under a global collaboration agreement. Kevzara is a fully-human monoclonal antibody. Kevzara binds specifically to the IL-6 receptor, and has been shown to inhibit IL-6-mediated signaling.

  • IL-6 is an immune system protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems.
  • Kevzara is being investigated for its ability to reduce the overactive inflammatory immune response associated with COVID-19 based on evidence of markedly elevated levels of IL-6 in severely ill patients infected with coronaviruses. 
  • Phase 2/3 trial initiated in Italy, Spain, Germany, France, Canada and Russia and is enrolling patients. Sanofi is leading trials outside the U.S., while Regeneron is leading U.S. trials

First patient outside U.S. treated in global Kevzara® (sarilumab) clinical trial program for patients with severe COVID-19″
https://www.sanofi.com/en/media-room/press-releases/2020/2020-03-30-07-00-00

  • About the Trial:
  • This Phase 2/3, randomized, double-blind, placebo-controlled trial uses an adaptive design to evaluate the safety and efficacy of Kevzara in adults hospitalized with serious complications from COVID-19.
  • To enter the trial, patients must have pneumonia and be hospitalized with laboratory-confirmed COVID-19 that is classified as severe or critical, or who are suffering from multi-organ dysfunction. After receiving the study dose, patients will be assessed for 60 days, or until hospital discharge or death.
  • In the Phase 2 part of the trial, patients will be randomized 2:2:1 into three groups: Kevzara higher dose, Kevzara lower dose and placebo.

    The Phase 2 findings will be utilized in an adaptive manner to determine transition into Phase 3, helping to determine the endpoints, patient numbers and doses.
  • If the trial continues with all three treatment arms to the end, it is expected to enroll approximately 300 patients, depending on the status of the COVID-19 outbreak and the proportion of patients with severe COVID-19.” https://clinicaltrials.gov/ct2/show/NCT04315298

Hydroxychloroquine:

 On 17-Mar 2020, the University of Minnesota announced to launch a clinical trial on a post-exposure treatment for coronavirus COVID-19 disease.

Hydroxychloroquine inhibits terminal glycosylation of ACE2, the receptor that SARS-CoV and SARS-CoV-2 target for cell entry.
https://med.umn.edu/news-events/covid-19-clinical-trial-launches-university-minnesota

Study objectives: it is a randomized interventional Phase II/III study

  1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus.
  2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
    https://clinicaltrials.gov/ct2/show/NCT04308668

Avigan

On 31-Mar-2020, FUJIFILM Toyama Chemical Co., Ltd. (President: Junji Okada) has announced the initiation of Phase III clinical trial to evaluate the safety and efficacy of influenza antiviral drug “Avigan Tablet” (generic name: favipiravir) in Japan for patients of COVID-19, a respiratory infection caused by the novel Coronavirus (SARS-CoV-2). 

Avigan, approved for manufacture and sale as an influenza antiviral drug in Japan, has a mechanism of action for selectively inhibiting RNA polymerase involved in influenza viral replication.

Due to this mechanism, it is expected that Avigan may potentially have an antiviral effect on the new coronavirus as it is classified into the same type of single-stranded RNA virus like influenza, and its clinical application to treat COVID-19 is now under study.”
https://www.fujifilm.com/jp/en/news/hq/3211

Avastin:

It is brand name for Bevacizumab. It is being tested by Qilu Hospital of Shandong University for COVID19

Mechanism of action: It acts by selectively binding circulating VEGF, thereby inhibiting the binding of VEGF to its cell surface receptors. This inhibition leads to a reduction in microvascular growth of tumor blood vessels and thus limits the blood supply to tumor tissues”

Study title: It is open level Phase 2/3 interventional study in Severe or Critical Patients With COVID-19 Pneumonia (BEST-CP)
https://clinicaltrials.gov/ct2/show/NCT04275414

Remdesivir:

 ” Remdesivir is a prodrug that metabolizes into its active form GS-441524.

  • An adenosine nucleotide analog, GS-441524 interferes with the action of viral RNA-dependent RNA polymerase and evades proofreading by viral exoribonuclease (ExoN), causing a decrease in viral RNA production. 
  • It was unknown whether it terminates RNA chains or causes mutations in them. However, it has been learned that the RNA-dependent RNA polymerase of Ebola virus is inhibited for the most part by delayed chain termination”
  • Gilead has initiated two Phase 3 clinical studies to evaluate the safety and efficacy of remdesivir in adults diagnosed with COVID-19 following the U.S. Food and Drug Administration’s (FDA) rapid review and acceptance of Gilead’s investigational new drug (IND) filing. 

Leronlimab (PRO140):


It is being tested for COVID19 by CytoDyn.

On March 27, 2020 CytoDyn Inc.(“CytoDyn” or the “Company”), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that three-day results post-leronlimab treatment of the first four patients under an Emergency Investigational New Drug (EIND) granted by the U.S. Food and Drug Administration (FDA).

A total of seven patients have been enrolled thus far under EIND in the same leading medical center in the New York City area. The treatment with leronlimab is targeted as a therapy for patients who experience respiratory complications as a result of contracting SARS-CoV-2 causing the Coronavirus Disease 2019 (COVID-19). 

Aviptadil:


On 29-Mar-2020, it was announced that “The US FDA has issued a “Study May Proceed” letter to NeuroRx, a Delaware Corporation within 24 hours of NeuroRx’s IND application. In partnership with Relief Therapeutics “

Randomized, placebo-controlled trial”
“Relief Therapeutics holds FDA and EU orphan drug designations for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis. Relief also holds a US patent”

Mechanism of action:
“Aviptadil is a patented form of Vasoactive Intestinal Polypeptide (VIP) VIP is known to have potent anti-cytokine effects in numerous animal models and in phase 1 and phase 2 human studies”


Study title: It is Phase II Randomized Interventional multicenter trial of Intravenous Aviptadil for COVID-19 Associated Acute Respiratory Distress (COVID-AIV).

https://relieftherapeutics.com/fda-grants-ind-study-may-proceed-for-covid-19-trial-to-neurorx-inc-in-partnership-with-relief-therapeutics-sixrlf-for-treatment-of-acute-respiratory-distress/
://clinicaltrials.gov/ct2/show/NCT04311697

SNG001:

It is Interferon beta which is being evaluated for COVID19 by Synairgen.

Mechanism of action: “Interferon beta (IFN-beta) is a naturally occurring protein, which orchestrates the body’s antiviral responses. There is evidence that deficiency in IFN-beta production by the lung could explain the enhanced susceptibility of these at-risk patient groups to developing severe lung disease during respiratory viral infections.

Furthermore, viruses, including coronaviruses, have evolved mechanisms which suppress endogenous IFN-beta production, thereby helping the virus evade the innate immune system.”

On the 18th March Synairgen announced that it has received expedited approvals from the Medicines and Healthcare products Regulatory Agency (MHRA) and Health Research Authority (HRA) to conduct a trial of SNG001 in COVID-19 patients.

Study objective: A randomised double-blind placebo-controlled Phase II trial to determine the safety and efficacy of inhaled SNG001 (IFNβ-1a for nebulisation) for the treatment of patients with confirmed SARS-CoV-2 infection (COVID-19)

https://www.synairgen.com/covid-19/
https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001023-14/GB

Fingolimod:

It is being evaluated by First Affiliated Hospital of Fujian Medical University

Mechanism of action: Fingolimod is a sphingosine 1-phosphate receptor modulator Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system

Study objective: It is Phase II Non-Randomized Open Label study to evaluate the Efficacy of Fingolimod in the Treatment of New Coronavirus Pneumonia (COVID-19).

https://clinicaltrials.gov/ct2/show/NCT04280588

AiRuiKa:

It is brand name of camrelizumab. It is being evaluated by Southeast Univ China

“A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1,) with immune checkpoint inhibitory and antineoplastic activities.

This prevents the activation of PD-1 and its downstream signalling pathways. This restores immune function through the activation of cytotoxic T lymphocytes (CTLs) and cell-mediated immune responses against tumor cells or pathogens.

Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.”

Study objective: It is interventional, Randomized, Phase II study to evaluate Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients. https://clinicaltrials.gov/ct2/show/NCT04268537

Mesenchymal stem cells:

The FDA has approved a clinical trial to study COVID-19 patients administered with umbilical cord-derived mesenchymal stem cells, which should prevent lung inflammation.

As per NEWS: An international team of scientists has been granted immediate US Food and Drug Administration (FDA) authorisation for a 24-patient clinical trial to test the safety and exploratory efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) to prevent the life-threatening lung inflammation that accompanies severe cases of COVID-19.

The cell therapy will be administered to patients intravenously.”
Various cell therapies are under investigation
https://link.springer.com/article/10.1007/s12015-020-09973-w/tables/

Losartan:

It is being evaluated by Univ.of Minnesota, an antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II. 


It is found that Losartan helps reduce inflammation in the lungs, which is the main cause of death from COVID-19 when that inflammation leads to acute respiratory distress syndrome or ARDS.

Study title: This is a multi-center, double-blinded Phase II study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
https://clinicaltrials.gov/ct2/show/NCT04312009

Gimsilumab:

It is being tested by Roivant Sciences for COVID 19.


Mechanism of action: “Gimsilumab is a fully human monoclonal antibody targeting GM-CSF. Gimsilumab has been tested in numerous non-clinical studies and two prior clinical studies, including a 4-week Phase 1 study in healthy volunteers conducted by Roivant which completed dosing in February. Gimsilumab has demonstrated a favorable safety and tolerability profile based on data collected to date.

On 15-April-2020, Roivant Sciences announced that the first patient was dosed at Temple University Hospital in Philadelphia in an adaptive, randomized, double-blind, placebo-controlled, multi-center pivotal trial evaluating the impact of intravenous (IV) treatment with gimsilumab on mortality in COVID-19 patients with lung injury or ARDS.

Dosing will commence at Mount Sinai Hospital in New York City and other trial sites imminently.

Study title: A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Phase I Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019.

https://roivant.com/roivant-doses-first-patient-in-pivotal-breathe-clinical-trial-evaluating-gimsilumab-in-covid-19-patients-for-the-prevention-and-treatment-of-acute-respiratory-distress-syndrome/
https://clinicaltrials.gov/ct2/show/NCT04351243?intr=Gimsilumab&draw=2&rank=1

Sylvant:

It is the brand name of Siltuximab. It is evaluated by EUSA Pharma of COVID 19.

“Siltuximab is an interleukin (IL)-6 targeted monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as well as in a number of other jurisdictions worldwide”

 On 01-April-2020, “EUSA Pharma, announced that initial preliminary findings from the Papa Giovanni XXIII Hospital sponsored SISCO (Siltuximab ISerious COVID-19) Study based on a pre-planned data analyis on 24 March 2020.

“The interim data, presented from the first 21 patients treated with siltuximab and followed for up to 7 days, show that one-third (33%, n=7) of patients experienced clinical improvement with a reduced need for oxygen support and 43% (n=9) of patients saw their condition stabilise, indicated by no clinically relevant changes.
Combined, this means that over three-quarters of patients treated with siltuximab (76%, n=16) had either stable or improved disease at this interim analysis. A worsening of the disease was seen in 3 (14%) patients whilst 1 (5%) patient died and 1 (5%) experienced a cerebrovascular event.”

Study title: An Observational Case-control Study of the Use of Siltuximab (SYLVANT) in Patients Diagnosed With COVID-19 Infection Who Have Developed Serious Respiratory Complications. Antibody from the recovered patient (plasmapheresis)
Many institutes/hospitals are testing antibody-rich plasma from the treatment of COVID19.

On 13-April-2020, FDA has issued guidance to provide recommendations to health care providers and investigators on the administration and study of investigational convalescent plasma collected from individuals who have recovered from COVID-19 (COVID-19 convalescent plasma) during the public health emergency.

https://www.eusapharma.com/news/interim-analysis-data-for-siltuximab-treated-covid-19-patients-from-the-sisco-study/
https://www.clinicaltrials.gov/ct2/show/NCT04322188
https://www.clinicaltrials.gov/ct2/show/NCT04322188
https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma

Vaccines for COVID 19

mRNA1273 ( 2019-nCoV Vaccine):

On March 16, 2020, the NIH announced that the first participant in its Phase 1 study for mRNA-1273 was dosed, a total of 63 days from sequence selection to first human dosing. This Phase 1 study will provide important data on the safety and immunogenicity of mRNA-1273.
Immunogenicity means the ability of the vaccine to induce an immune response in participants. The open-label trial is expected to enroll 45 healthy adult volunteers ages 18 to 55 years over approximately six weeks.

On March 27, 2020, the NIH announced that Emory University in Atlanta will begin enrolling healthy adult volunteers ages 18 to 55 years in the NIH-led Phase 1 study of mRNA-1273. 

Please check all the sequence of an event on below link: https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19 Study:https://clinicaltrials.gov/ct2/show/NCT04283461

Ad5-nCoV:

Ad5-nCoV is coronavirus vaccine for COVID-19 in a Phase 1 Clinical Trial in China.
CanSinoBIO’s adenovirus-based viral vector vaccine technology platform is used to manufacture this vaccine.

It is a genetically engineered vaccine candidate with the replication-defective adenovirus type 5 as the vector to express SARS-CoV-2 spike protein.

https://www.precisionvaccinations.com/vaccines/ad5-ncov-covid-19-vacci

chadox1 ncov19:

On 31-Mar-2020, University of Oxford initiated enrollment of healthy participants in a trial testing the COVID-19 vaccine candidate called ChAdOx1 nCoV-19.

Originally developed to target MERS, it is based on an adenovirus vaccine vector and the COVID-19 spike protein.

Study title: A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers.
https://www.clinicaltrials.gov/ct2/show/NCT04324606

LV SMENP-DC:

LV-SMENP-DC vaccine is made by modifying DC with lentivirus vectors expressing COVID-19 minigene SMENP and immune-modulatory genes.

CTLs will be activated by LV-DC presenting COVID-19 specific antigens.

Study title: Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of COVID-19 Coronavirus.
https://clinicaltrials.gov/ct2/show/NCT04276896

BCG vaccines (Bacille Calmette-Guérin):

On 12 April 2020, WHO announced that there is no evidence that the Bacille Calmette-Guérin vaccine (BCG) protects people against infection with COVID-19 virus.

Two clinical trials addressing this question are underway, and WHO will evaluate the evidence when it is available. In the absence of evidence, WHO does not recommend BCG vaccination for the prevention of COVID-19.
WHO continues to recommend neonatal BCG vaccination in countries or settings with a high incidence of tuberculosis

Study title: being sponsored by Murdoch Childrens Research Institute. two groups, multicentre, open-label randomised controlled phase II/II trial to evaluate.
BCG Vaccination to Reduce the Impact of COVID-19 in Australian Healthcare Workers Following Coronavirus Exposure (BRACE) Trial.

https://clinicaltrials.gov/ct2/show/NCT04327206

There are many other studies with BCG vaccine for COVID19 as given below:

Application of BCG Vaccine for Immune-prophylaxis Among Egyptian Healthcare Workers During the Pandemic of COVID-19
https://clinicaltrials.gov/ct2/show/NCT04350931?intr=BCG+vaccine&draw=2&rank=1

Reducing Health Care Workers Absenteeism in Covid-19 Pandemic Through BCG Vaccine (BCG-CORONA)
https://clinicaltrials.gov/ct2/show/NCT04328441?intr=BCG+v

More Source to get information about recent COVID 19 treatment:

DRAFT landscape of COVID-19 candidate vaccines – 23 April 2020
https://www.who.int/blueprint/priority-diseases/key-action/draft-landscape-COVID-19-candidate-vaccines-23-April-2020.pdf

Coronavirus treatment: List of Vaccines and drugs in the pipeline for COVID-19
https://lifepronow.com/blog/2020/04/20/coronavirus-treatment-vaccines-and-drugs-in-the-pipeline-for-covid-19/

List of all studies registered with clinicaltrial.gov
https://clinicaltrials.gov/ct2/results?cond=COVID19&term=&type=&rslt=&age_v=&gndr=&intr=&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&rsub=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=

Coronavirus treatment: List of Vaccines and drugs in the pipeline for COVID-19

0

As the number of confirmed cases of COVID-19 continues to rise, healthcare researchers around the world are working tirelessly to discover new life-saving innovations in medicine.

Here are some companies and institutions developing new treatment options for COVID-19

Vaccine Company name Type of Vaccine Phase of study Study link
mRNA1273  (2019-nCoV Vaccine)   Emory University in Atlanta RNA Phase I https://clinicaltrials.gov/ct2/show/NCT04283461
Ad5-nCoV Cansino Bio  Non replicating viral vector Phase I https://www.precisionvaccinations.com/vaccines/ad5-ncov-covid-19-vacci
  chadox1 ncov19 University of Oxford Non replicating viral vector Phase I/II https://www.clinicaltrials.gov/ct2/show/NCT04324606
LVSMENP-DC Shenzhen Geno immune medical institute lentiviral Phase I/II https://clinicaltrials.gov/ct2/show/NCT04276896
BCG vaccines (Bacille Calmette-Guérin)   Murdoch Childrens Research Institute. Live Attenuated virus Phase II/III https://clinicaltrials.gov/ct2/show/NCT04327206
     Drug Company name Mechanism of action Phase of study Study link
Sylvant
(Siltuximab)
EUSA Pharma interleukin (IL)-6 inhibitor Observational study   https://www.clinicaltrials.gov/ct2/show/NCT04322188  
Gimsilumab Roivant monoclonal antibody targeting GM-CSF Phase I https://clinicaltrials.gov/ct2/show/NCT04351243?intr=Gimsilumab&draw=2&rank=1
Losartan Univ. of Minnesota ANGIOTENSIN TYPE 1 RECEPTOR inhibitor Phase II https://clinicaltrials.gov/ct2/show/NCT04312009
AiRuiKa (camrelizumab) Southeast Univ China PD-1 inhibitor Phase II https://clinicaltrials.gov/ct2/show/NCT04268537
Fingolimod    First Affiliated Hospital of Fujian Medical University Sphingosine 1-phosphate receptor modulator Phase II https://clinicaltrials.gov/ct2/show/NCT04280588
SNG001 Synairgen IFN-beta 1a Sphingosine phosphate receptor modulator Phase II https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001023-14/GB
Kaletra AbbVie’s HIV protease. Failed trial https://news.abbvie.com/news/press-releases/abbvie-partnering-with-global-authorities-to-determine-efficacy-hiv-drug-in-treating-covid-19.htm
Ganovo + Ritonavir Ascletis HCV NS3/4A protease inhibitor. Phase IV https://clinicaltrials.gov/ct2/show/NCT04345276?
Actemra (Tocilizumab) Roche IL-6 receptors inhibitor Phase III https://clinicaltrials.gov/ct2/show/NCT04351152?intr=Lenzilumab&draw=2&rank=2  
CD24Fc Oncoimmune  modulate immune  responses Phase III https://clinicaltrials.gov/ct2/show/NCT04317040?intr=CD24Fc&draw=2&rank=2
Prezcobix Shanghai Public health clinical centre HIV protease inhibitor Phase III https://clinicaltrials.gov/ct2/show/NCT04252274
Colchine The Montreal Heart Institute (MHI) Research Centre Tubulin Disruption Phase III https://clinicaltrials.gov/ct2/show/NCT04322682
Kevzara (sarilumab) Sanofi and Regeneron IL-6 receptor Phase 2/3 https://clinicaltrials.gov/ct2/show/NCT04315298
 Hydroxychloroquine University of Minnesota ACE2 inhibitor Phase II/III https://clinicaltrials.gov/ct2/show/NCT04308668  
Avigan FUJIFILM RNA polymerase inhibitor Phase III https://www.fujifilm.com/jp/en/news/hq/3211
Avastin (Bevacizumab)  Qilu Hospital of Shandong University VEGF inhibitor Phase 2/3   https://clinicaltrials.gov/ct2/show/NCT04275414
Remdesivir Gilead Adenosine analouge Phase III https://clinicaltrials.gov/ct2/show/NCT04292730?intr=remdesivir&lead=Gilead&draw=2&rank=3
Leronlimab (PRO140) CytoDyn CCR5antagonist Phase 2b/3 https://clinicaltrials.gov/ct2/show/NCT04347239?intr=Leronlimab&draw=2&rank=3
Aviptadil NeuroRx IL-6 inhibitor Phase II https://clinicaltrials.gov/ct2/show/NCT04311697

Lenzilumab

Humanigen
Anti GM-CSF
Phase III



https://clinicaltrials.gov/ct2/show/NCT04351152?intr=Lenzilumab&draw=2&rank=2

Mesenchymal stem cells
various instituteTissue regenerationPhase I
https://link.springer.com/article/10.1007/s12015-020-09973-w/tables/1

EMA review of Picato concludes medicine’s risks outweigh its benefits

0

April 17, 2020: “EMA’s safety committee (PRAC) has confirmed that Picato (ingenol mebutate), a gel for treating the skin condition actinic keratosis, may increase the risk of skin cancer and concluded that the risks of the medicine outweigh its benefits.

The conclusions are based on a review of all available data on the risk of skin cancer in patients using Picato, including results of a study comparing Picato with imiquimod (another medicine for actinic keratosis).

The study showed a higher occurrence of skin cancers, especially squamous cell carcinoma, in areas of skin treated with Picato than in areas treated with imiquimod. The Committee also considered that Picato’s effectiveness is not maintained over time and noted that other treatment options are available for actinic keratosis. Picato is no longer authorised in the EU.

In January 2020, Picato was suspended as a precaution while the review was underway. On 11 February 2020, the marketing authorisation was withdrawn at the request of LEO Laboratories Ltd, the company that marketed the medicine. Patients who have been treated with Picato should look out for unusual skin changes or growths, which may occur from weeks to months after use, and seek medical advice if any occur. Patients who have questions or concerns about their treatment should consult their doctor or pharmacist.

https://www.ema.europa.eu/en/documents/press-release/ema-review-picato-concludes-medicines-risks-outweigh-its-benefits_en.pdf

COVID-19 therapy, vaccine, epidemiology and policy development research boosted by twenty-one new projects

0

April 17, 2020:”Twenty-one new studies into the novel coronavirus have been funded by the UK government, including the first clinical drug trial in primary care, vaccine and therapy development, and studying epidemiology, disease transmission, behavioural interventions and policy approaches to COVID-19.   

This second round of projects receive £14.1 million as part of the £24.6 million rapid research response funded by UK Research and Innovation (UKRI), and by the Department of Health and Social Care through the National Institute for Health Research (NIHR).    

These projects build on the UK’s world-class expertise and capability in global heath and infectious disease that has already shaped our understanding of the pandemic and is informing measures to tackle it. They support the UK government’s efforts to save lives, protect the vulnerable and support the NHS so it can help those who need it the most.  

UKRI Chief Executive, Professor Sir Mark Walport said: “The research community’s response to the Covid-19 crisis has been outstanding. In a matter of weeks, researchers have formed projects to develop potential vaccines, repurpose existing drugs and explore the potential for new medicines, and to examine how the virus is transmitted and causes wide variation in symptoms. Pre-clinical trials of vaccines and clinical trials of drugs are already underway. 

“The pace at which this work has been carried out is tribute to the UK’s world-class research base and its dedication to the fight against this disease.” 

Jonathan Sheffield, NIHR Covid-19 Research Operations Director, said: “In just a few weeks the UK’s health and science communities have risen to the challenges presented by Covid-19 in deeply inspiring ways. Alongside the selfless work being done by our amazing frontline NHS staff, our world-leading research community is also putting its cutting-edge expertise to use in myriad ways.  

“Though the studies announced today may vary in theme, they all represent some of the best and brightest scientific research into Covid-19 being done anywhere in the world.” 

The projects will run over a maximum 18-month period, ensuring timely insights into the current epidemic.  

This research funding has been coordinated with other funders and the World Health Organization to ensure there is not duplication of effort and expertise is applied strategically.  

On 30 March, UKRI and NIHR launched a joint rolling call for researchers to apply for funding for short-term projects addressing and mitigating the health, social, economic, cultural and environmental impacts of the COVID-19 outbreak. 

Research projects funded: 
Clinical trial 

Professor Christopher Butler, University of Oxford, £1.7 million: The first clinical trial in COVID-19 patients consulting in primary care, ‘PRINCIPLE’, will initially test if the anti-malarial drug hydroxychloroquine can reduce the need for people to go to hospital or speed up their recovery. They will recruit patients aged over 65 years (or aged 50-64 years with underlying health conditions), who consult in primary care (this trial is a national platform trial and is potentially available to all GP practices in the UK) and have COVID-19 symptoms. Patients will be tested for COVID-19 where possible, and will receive either the usual care provided plus hydroxychloroquine 200mg twice a day for 7 days, or, soon, azithromycin for 3-5 days, or usual supportive care without any experimental treatment. The trial aims to recruit over 3,000 people, and has been designed to be flexible, so new suitable treatments can be added into the trial when these become available.  

Vaccine development  
Prof Robin Shattock, Imperial College London, £1.7 million: They have developed a promising RNA vaccine. When it’s injected, it will deliver the genetic instructions to muscle cells to make the SARS-CoV-2 ‘spike’ surface protein, which should provoke an immune response and create immunity to the virus. They have modified the RNA sequence to create a stabilised version of the spike protein, which they hope will provoke the body to produce more protective antibodies. This funding will enable to them to take the vaccine through GMP manufacturing, testing in animal models for safety and efficacy, regulatory and ethical approval, and, if that’s successful, a phase I clinical trial in healthy human volunteers.   
 

Professor Miles Carroll, Public Health England, £0.4 million: They will develop an animal model of SARS-CoV-2 infection in non-human primates, which can be used to test if new vaccines and therapies are effective and, importantly, safe. This will enable researchers to address concerns that vaccines that enhance the immune response could potentially worsen COVID-19.  

Therapy development  
Dr Stuart Dowall, Public Health England, £0.4 million: Antibodies can bind proteins on the virus surface and disrupt entry into cells. The team aim to create a purified ovine immunoglobulin preparation consisting of polyclonal antibodies (which recognise multiple areas on the target to reduce the chance of escape mutations occurring) by immunising sheep with the SARS-CoV-2 spike protein. The purified ovine immunoglobulin will then be tested for activity to bind and neutralise SARS-CoV-2 virus before testing in animals to determine if it offers protection against infection and disease progression.  

Antibody testing  
Professor Richard Tedder, Imperial College London, £0.4 million: Using the same techniques as previously applied to Zika and Ebola, the team will develop a non-invasive test, using a sample of fluid from the mouth, to detect the immune antibodies (IgG and IgM) that indicate a person has been infected with SARS-CoV-2. They aim to develop a test within 6 months that could be used to diagnose people who have had SARS-CoV-2.  

Population surveillance   
Understanding the prevalence of COVID-19 infections in the community is necessary for NHS planning and the public health response. Information collected by these studies includes: how many people become infected, how many of them become ill, what their symptoms are, how many seek health care, how commonly they transmit to household contacts, what proportion need hospitalisation and what proportion die.  

Professor Andrew Hayward, University College London, £3.2 million: This study ‘Virus Watch’ will study 25,000 individuals across the country in a nationally representative household cohort (April to March 2021). Within this cohort, 10,000 people will be tested for SARS-CoV-2 and other circulating viruses every time they report symptoms that could be caused by COVID-19. When antibody tests are available, participants will be invited to have these tests to understand who has been infected and to measure the protective effect of antibodies. All participants will provide information on symptoms and behaviour and there will be an optional mobile app for analysis of movement patterns to help understand how social distancing measures affect the risk of infection. 
 

Dr Eleni Nastouli, University College London, £1.5 million: 200 healthcare workers at University College London Hospitals NHS Foundation Trust will be tested for SARS-CoV-2 repeatedly over time to assess the risk of acquiring the infection. They will also study healthcare worker behaviour, using digital tracking systems and interviews, and use this data to better inform health and safety measures to protect staff and patients, and hospital infection prevention and control. Ethical questions around staff testing and infection control measures will also be addressed. The team plans to use the data to advise on policy for the current pandemic and preparedness for future ones.  

Professor Matthew Snape, Oxford Vaccine Group, University of Oxford, £0.6 million: With Public Health England, they will use an existing study of infectious disease immunity in children and teenagers 0 to 19 years old to study the presence of antibodies against COVID-19 (a marker of having had the disease and now having immunity) in approximately 400 children and teenagers per month for the duration of the COVID-19 outbreak, and they will collect information on recent respiratory illnesses and relevant medical history.  
 

Professor Aziz Sheikh, University of Edinburgh, £0.5 million: Using anonymised electronic health records (including GP and hospital visits and test results) from 1.2 million people in Scotland, they will track the progress of the COVID-19 epidemic in near real-time. They will also process blood samples and swabs of the virus taken from a sub-sample of the participants, to determine who has been exposed and to sequence the virus genomes. If vaccines or anti-viral therapies become available, their effectiveness will be monitored.  
 
Professor Christoph Lees and Dr Ed Mullins, Imperial College London, £0.3 million: To better understand some specific research questions as to how COVID-19 affects early pregnancy, fetal growth, prematurity and virus transmission to the baby the researchers will construct a registry of women with suspected and confirmed COVID-19 from early pregnancy to after delivery of the baby. Healthcare professionals from the UK and across many international centres will contribute data via a web portal.  
 

Behaviour and policy research  
Professor Isabel Oliver, Public Health England, £0.4 million: They will evaluate the public health measures, specifically they will conduct surveys and interviews to assess the effectiveness and impacts of the 14 day self-isolation advice on mental health and wellbeing. They will also develop and test different messages to encourage people to follow public health advice, to better inform the current public health response. 

Professor Jane Duckett, University of Glasgow, £0.3 million: The research team will study Chinese policy documents and social media databases, and will conduct local interviews in four regions of China. They will document in detail Chinese central and local government measures to tackle the COVID-19 epidemic and evaluate their societal impacts – to inform the international response.  

Professor Trudie Lang, University of Oxford, £0.3 million: Building on lessons learnt in the Zika and Ebola outbreaks, the Global Health Network will deliver and share trusted research tools, guidance and training, for example providing guidance on how to run studies in local clinics and hospitals. They will work with partners internationally to create lasting research networks to support evidence generation in challenging settings, so that better quality, standardised data is shared faster worldwide.  
 

Professor Sally Sheard, University of Liverpool, and Dr Nina Gobat, University of Oxford, £0.3 million: Working with colleagues at the University of Oxford, they will analyse the UK pandemic response by collecting real-time responses from senior policymakers and stakeholders (PHE, DHSC, NHS) and the frontline experiences of healthcare workers, and by studying media and document sources. Their findings will inform senior policymakers.   
 

Professor Lucy Yardley, University of Southampton and University of Bristol, £0.2 million: The ‘Germ-Defence’ website was shown to reduce infection transmission in the home in the swine flu pandemic and seasonal flu years, and will now be rapidly adapted for COVID-19 using novel methods of public engagement and feedback. It will be disseminated in the UK and internationally, evaluating its effects on infection control attitudes and behaviour.  

Virology  
Allan Bennett, Public Health England, £0.3 million: They will study how SARS-CoV-2 can be transmitted, by determining how long SARS-CoV-2 can survive in the air and on different types of surfaces (for example, those found in the healthcare, domestic and community settings) under controlled environmental conditions (a range of temperatures and humidities) representative of those found in different settings and countries. Methods of decontamination will also be investigated.  
Dr Sumana Sanyal, University of Oxford, £0.2 million: The virus, SARS-CoV-2, uses enzymes within infected cells called proteases (enzymes which cut up other proteins), so it can replicate and spread. This study will identify which proteases are necessary for the virus, to provide targets for future drugs and vaccine development.  

Transmission and mathematical modelling  
Dr John Edmunds, London School of Hygiene & Tropical Medicine, £0.5 million: To provide modelling support, including real-time forecasting and scenario analyses, to help improve decisions about the control of COVID-19. In addition, to undertake behavioural surveillance to help track adherence to social distancing measures and how this affects the rate of disease spread within the UK.    

Professor Martie van Tongeren, The University of Manchester, £0.3 million: They will investigate the role of gig workers, in particular delivery workers, and delivery supply chains in preventing disease transmission. The project will use interviews with workers and data on deliveries to construct mathematical models to determine how the delivery sector contributes to minimising the risk of spreading the disease and the benefits of additional measures to protect the workers.    

Dr Leon Danon, University of Exeter, £0.2 million: The researchers will adapt and develop mathematical models of disease spread and movement within the UK to evaluate the impact of control and mitigation strategies, including travel restrictions, border screening and quarantine policies, and to predict where and when the disease will spread.    

Dr Anne Presanis, MRC Biostatistics Unit, University of Cambridge, £0.2 million: To understand the severity of the epidemic – such as the proportion of infections that result in hospitalisation or death – they will use Bayesian statistical models to combine information from multiple datasets emerging from various sources, such as numbers accessing healthcare, numbers of deaths, population surveillance data, and cohort and household studies.   

These projects are in addition to six projects funded in the first round which were announced on 23 March. 
The NIHR has established a national prioritisation process for COVID-19 research that involves the healthcare system – to prevent duplication of effort and ensure that resources and capacity are not exceeded – and a list of prioritised studies can be found on the NIHR website.”

https://www.ukri.org/news/covid-19-research-boosted-by-new-projects/

FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer

0

April 17, 2020: “The U.S. Food and Drug Administration approved Tukysa (tucatinib) in combination with chemotherapy (trastuzumab and capecitabine) for the treatment of adult patients with advanced forms of HER2-positive breast cancer that can’t be removed with surgery, or has spread to other parts of the body, including the brain, and who have received one or more prior treatments.

The FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland) on this review. This is the first Project Orbis partnership between the FDA, HSA and Swissmedic. While the FDA approved Tukysa today, the application is still under review at the other agencies. Collaboration among international regulators may allow patients with cancer to receive earlier access to products in other countries where there may be significant delays in regulatory submissions, regardless of whether the product has received FDA approval. Early availability of new therapies and adoption as standard of care around the world may have an impact on the increasingly international conduct of cancer clinical trials, potentially accelerating the development of anticancer products. With a framework for concurrent submission and review of oncology drugs, Project Orbis facilitates a collaborative review to identify any regulatory divergence across review teams.”

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators. We are pleased to work with our Singapore and Switzerland colleagues for the first time, and to continue working alongside our Australian and Canadian colleagues as we facilitate new treatment options for patients – like today’s first new molecular entity under Project Orbis,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “This approval represents an additional targeted treatment option for patients with HER2-positive breast cancer. The clinical trial supporting this approval enrolled and specifically studied patients with active brain metastases in addition to the overall population enrolled, which also demonstrated benefit in this subgroup.”

“HER2-positive breast cancer, which makes up approximately one-fifth of breast cancers, has too much of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. More than 25% of women with metastatic HER2-positive breast cancer will develop brain metastases.

“We recognize that patients with cancer constitute a vulnerable population at risk of contracting the coronavirus disease,” said Pazdur. “In this critical time, we remain steadfast in our commitment to patients with cancer and doing everything we can to expedite oncology product development. Tukysa was approved four months prior to the FDA goal date, providing an example of this commitment and showing how our regular work in reviewing treatments for patients with cancer is moving forward without delay.”

Tukysa is a kinase inhibitor meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Tukysa is approved for treatment after patients have taken one or more anti-HER2-based regimens in the metastatic setting. The FDA approved Tukysa based on the results of a clinical trial enrolling 612 patients who had HER2-positive advanced unresectable or metastatic breast cancer and had prior treatment with trastuzumab, pertuzumab and ado-trastuzumab emtansine (T-DM1). Patients with previously treated and stable brain metastases, as well as those with previously treated and growing or untreated brain metastases, were eligible for the clinical trial, and 48% of enrolled patients had brain metastases at the start of the trial.

The primary endpoint was progression-free survival (PFS), or the amount of time when there was no growth of the tumor. The median PFS in patients who received Tukysa, trastuzumab, and capecitabine was 7.8 months compared to 5.6 months in those patients who received placebo, trastuzumab, and capecitabine. Overall survival and PFS in patients with brain metastases at baseline were key secondary endpoints. The median overall survival in patients who received Tukysa, trastuzumab, and capecitabine was 21.9 months compared to 17.4 months in patients who received placebo, trastuzumab, and capecitabine. The median PFS in patients with brain metastases at baseline who received Tukysa, trastuzumab and capecitabine was 7.6 months compared to 5.4 months in patients who received placebo, trastuzumab and capecitabine.

Common side effects for patients taking Tukysa were diarrhea, palmar-plantar erythrodysesthesia (burning or tingling discomfort in the hands and feet), nausea, fatigue, hepatotoxicity (liver damage), vomiting, stomatitis (inflammation of the mouth and lips), decreased appetite, abdominal pain, headache, anemia and rash.

Tukysa can cause serious side effects including severe diarrhea associated with dehydration, acute kidney injury and death. Health care professionals should advise patients to notify their health care provider and start antidiarrheals as clinically indicated if diarrhea occurs. If patients are experiencing severe diarrhea, Tukysa should be interrupted or the dosage reduced. Tukysa can also cause severe hepatotoxicity. Health care professionals should monitor liver tests in patients taking Tukysa every three weeks while the patient is on treatment or as clinically indicated.

Women who are pregnant or breastfeeding should not take Tukysa because it may cause harm to a developing fetus or newborn baby. The FDA advises health care professionals to tell females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Tukysa and for at least one week after the last dose. The FDA also advises patients refer to the Full Prescribing Information of trastuzumab and capecitabine for pregnancy and contraception information.

In addition to the international collaboration with TGA, Health Canada, HSA Singapore and SMC Switzerland, this review used the Real-Time Oncology Review (RTOR) pilot program, which can streamline the submission of data prior to the completion and submission of the entire clinical application. RTOR, as well as the Assessment Aid, facilitated discussions among the regulatory agencies and regulatory review.

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Tukysa was also granted Fast Track designation, which expedites the review of drugs to treat serious conditions and fill an unmet medical need. Tukysa received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-drug-under-international-collaboration-treatment-option-patients-her2

FDA Approves First Targeted Treatment for Patients with Cholangiocarcinoma, a Cancer of Bile Ducts

0

April 17, 2020: “The U.S. Food and Drug Administration granted accelerated approval to Pemazyre (pemigatinib), the first treatment approved for adults with certain types of previously treated, advanced cholangiocarcinoma.

“This approval demonstrates that while we continue to focus our efforts on addressing the COVID-19 pandemic, the FDA remains committed to the important work of reviewing treatments for patients with cancer and other serious conditions,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “With Pemazyre, we considered the observed efficacy results to be clinically meaningful and the overall risk to benefit assessment for patients with tumors harboring FGFR2 gene fusions and other rearrangements to be favorable, particularly when we considered that these patients have no other good options following first line treatment with chemotherapy.”

Cholangiocarcinoma is a rare form of cancer that forms in bile ducts, which are slender tubes that carry the digestive fluid bile from the liver to gallbladder and small intestine. Today’s approval is for patients with cholangiocarcinoma that is locally advanced (when cancer has grown outside the organ it started in, but has not yet spread to distant parts of the body) or metastatic (when cancer cells spread to other parts of the body) and who have tumors that have a fusion or other rearrangement of a gene called fibroblast growth factor receptor 2 (FGFR2).

At diagnosis, a majority of patients with cholangiocarcinoma have advanced disease, meaning that the disease is no longer treatable with surgery. For these patients, until today, there have been no FDA-approved therapies; a combination of chemotherapy drugs has been the standard initial treatment. FGFR2 fusions have been found in the tumors of approximately 9% to 14% of patients with cholangiocarcinoma. Pemazyre is a tablet that works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

Pemazyre’s approval was based on the results of a clinical trial that enrolled 107 patients with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement who had received prior treatment. During the clinical trial, patients received Pemazyre once a day for 14 consecutive days, followed by 7 days off, in 21-day cycles until the disease progressed or the patient experienced an unreasonable level of side effects. To assess how well Pemazyre was working during the trial, patients were scanned every eight weeks. The trial used established criteria to measure how many patients experienced a complete or partial shrinkage of their tumors during treatment (overall response rate). The overall response rate was 36%, with 2.8% of patients having a complete response and 33% having a partial response. Among the 38 patients who had a response, 24 patients (63%) had a response lasting 6 months or longer and 7 patients (18%) had a response lasting 12 months or longer. 

The most common adverse reactions occurring in 20% or more of patients who received Pemazyre are hyperphosphatemia and hypophosphatemia (electrolyte disorders), alopecia (spot baldness), diarrhea, nail toxicity, fatigue, dysgeusia (taste distortion), nausea, constipation, stomatitis (sore or inflammation inside the mouth), dry eye, dry mouth, decreased appetite, vomiting, joint pain, abdominal pain, back pain and dry skin. Ocular (eye) toxicity is also a risk of Pemazyre.

The FDA granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Pemazyre received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. As a condition of the accelerated approval, the sponsor will complete and submit the results of a randomized trial demonstrating an

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-treatment-patients-cholangiocarcinoma-cancer-bile-ducts

 

Miami-Dade Transit Workers File Lawsuit, Allege ‘Life-Threatening’ Violations During Pandemic

0

April 17, 2020: “Transit workers in Miami-Dade County have filed a lawsuit asking for immediate action to fix what they call “life-threatening” violations by the county’s public transportation system during the coronavirus pandemic.

The lawsuit, filed Friday by the transit workers union representing nearly 3,000 employees, asks for Transit Director Alice Bravo to make changes it says need to be in place to keep workers safe.

Workers claim, among several items, that officials have not provided them with sufficient masks, gloves and other protective gear. They say buses and rail cars are not properly sanitized and social distancing protocols are not being enforced.

“Bus operators and other transit employees are not receiving sufficient PPE, social distancing protocols are not being enforced, and some buses are dangerously overcrowded,” said union president Jeffery Mitchell in a statement. “We had no choice but to sue – lives are at risk.”

Union officials say they have been complaining for weeks about protocols from the Centers for Disease Control and Prevention not being followed.”

“Our transit employees are dedicated public servants risking their lives on the front lines,” Mitchell said. “Our passengers are loyal and deserve the highest level of protection. “

https://www.nbcmiami.com/news/local/miami-dade-transit-workers-file-lawsuit-allege-life-threatening-violations-during-pandemic/2221159/

 

FDA Approves Baptist Health In-House Coronavirus Testing

0

April 17, 2020:The Food and Drug Administration has granted a South Florida hospital emergency permission to perform COVID-19 swab tests within its own in-house laboratory. Baptist Health South Florida is the first organization in Florida – and one of 12 in the country – to receive the emergency authorization.

Officials with Baptist say the Hospital of Miami Molecular Diagnostic Laboratory will be able to perform 40 to 80 in-house tests every day – with results being received within 24 hours.

“Having this test allows us to expand our in-house testing capability, allowing us to make treatment decisions more quickly and quarantine patients appropriately,” said Edwin Gould, M.D., chief of pathology, Miami Cancer Institute. “We were fortunate to have all the highly sophisticated equipment and expertise needed already in-house– making the switch possible in a short timeframe.” 

The in-house testing allows the hospital to slowly wean itself off relying on private labs for test results, which can take days. Other hospital laboratories who have received the emergency authorization include Stanford Health Care, Northwestern Medicine, Yale New Haven Medicine and Children’s Hospital of Philadelphia.
https://www.nbcmiami.com/news/local/fda-approves-baptist-health-in-house-coronavirus-testing/2221239/