Companies Developing COVID-19 Therapies

Adaptive Biotechnologies and Microsoft launch groundbreaking ImmuneCODE database to share populationwide immune response to the COVID-19 virus - Adaptive Biotechnologies Corp. on June 11 launched ImmuneCODE with Microsoft Corp. to begin sharing one of the largest, most detailed views of the immune response to COVID-19 in real time based on de-identified data generated from thousands of COVID-19 blood samples from patients around the globe. The open database contains detailed information on the extraordinarily diverse set of T cells shown to specifically recognize unique features of the COVID-19 virus, called antigens, with unprecedented speed and scale. See also: Adaptive Biotechnologies and Microsoft expand partnership to decode COVID-19 immune response and provide open data access 

Adaptive Biotechnologies Launches immunoSEQ T-MAP COVID, First Molecular T Cell Monitoring Tool for SARS-CoV-2 - Adaptive Biotechnologies announced August 4 the launch of immunoSEQ^® T-MAP™ COVID, a proprietary research product and data analysis service to accurately and reproducibly measure the T-cell immune response to vaccines in development and track the persistence of that response over time. This product leverages data by Snyder et al., made available today that map T cells from over 1,000 patients to specific SARS-CoV-2 antigens that elicit an immune response. These data also demonstrate that SARS-CoV-2-specific T cells are persisting in recovered patients for over 90 days, adding important information to the ongoing effort to define immunity to COVID-19.

Amgen And Adaptive Biotechnologies Announce Strategic Partnership To Develop A Therapeutic To Prevent Or Treat COVID-19 - Adaptive will extend its high throughput platform to rapidly screen the massive genetic diversity of the B cell receptors from individuals that have recovered from COVID-19. This enables the identification of tens of thousands of naturally occurring antibodies from survivors of COVID-19 to select those that neutralize SARS-CoV-2.

Vir and Alnylam Expand Collaboration to Advance Investigational RNAi Therapeutics Targeting Host Factors for the Treatment of COVID-19 - Under their agreement, the companies will utilize Alnylam’s recent advances in lung delivery of novel conjugates of siRNA – the molecules that mediate RNAi – together with Vir’s infectious disease expertise and established capabilities, to bring forward one or more siRNAs to treat SARS-CoV-2 and potentially other coronaviruses as well. The collaboration will focus on development of siRNAs that Alnylam recently identified that target highly conserved regions of coronavirus RNAs.The two named targets include angiotensin converting enzyme-2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2). ACE2 is known to be the viral entry receptor for SARS-CoV-2 and other coronaviruses, while TMPRSS2 is believed to cleave the SARS-CoV-2 spike protein to facilitate cellular attachment. 

See also Vir Biotechnology's entry in the Company Directory.

Disease/Category-Specific EA Policies/Criteria

http://www.alnylam.com/medical-professionals/expanded-access-program/

Amgen And Adaptive Biotechnologies Announce Strategic Partnership To Develop A Therapeutic To Prevent Or Treat COVID-19 - Adaptive will extend its high throughput platform to rapidly screen the massive genetic diversity of the B cell receptors from individuals that have recovered from COVID-19. This enables the identification of tens of thousands of naturally occurring antibodies from survivors of COVID-19 to select those that neutralize SARS-CoV-2. Amgen will then leverage its world-class antibody engineering and drug development capabilities to select, develop and manufacture antibodies designed to bind and neutralize SARS-CoV-2. deCODE Genetics, a subsidiary of Amgen located in Iceland, will provide genetic insights from patients who were previously infected with COVID-19.

See also Adaptive Biotechnologies entry in the Company Directory

Applied Therapeutics Announces IND and Investigator-Initiated Studies of AT-001 in Critical COVID-19 Patients - A COVID-19 IND has been opened with the FDA for AT-001, a novel potent Aldose Reductase inhibitor in global Phase 3 development for Diabetic Cardiomyopathy. Multiple AT-001 investigator-initiated trials are now underway to address acute lung inflammation and cardiomyopathy in critical COVID-19 patients. Several New York City hospitals have initiated Emergency Investigational Drug applications for AT-001 use in critical COVID-19 patients.  AT-001 is currently being accessed in these New York City hospitals via “Named Patient” Emergency INDs or Investigator-Initiated Trials, depending on the patient circumstance and hospital institution.  Institutions that have initiated trials include Mount Sinai, NYU, and Columbia. To date, all patients treated under Emergency INDs have demonstrated improvement in cardiopulmonary function.  Additional data is being gathered through studies on the effect of AT-001 therapy in critical COVID-19 patients.

See also: Cardiovascular Effects of COVID-19

Results from First Clinical Study Using Danoprevir to Treat Naive and Experienced COVID-19 Patients - The data from this small-sample clinical study showed that danoprevir combined with ritonavir is safe and well tolerated in all patients. After 4 to 12-day treatment of danoprevir combined with ritonavir, all eleven moderate COVID-19 patients enrolled, two naive and nine experienced, were discharged from the hospital as they met all four conditions as follows: (1) normal body temperature for at least 3 days; (2) significantly improved respiratory symptoms; (3) lung imaging shows obvious absorption and recovery of acute exudative lesion; and (4) two consecutive RT-PCR negative tests of SARS-CoV-2 nucleotide acid (respiratory track sampling with interval at least one day).

Progress of the Small Sample Clinical Trial of Ganovo® and Ritonavir Combination Therapy on Novel Coronavirus Pneumonia

COVID-19 vaccine AZD1222 clinical trials resumed in the UK - Clinical trials for the AstraZeneca Oxford coronavirus vaccine, AZD1222, have resumed in the UK following confirmation by the Medicines Health Regulatory Authority (MHRA) that it was safe to do so. On 6 September, the standard review process triggered a voluntary pause to vaccination across all global trials to allow review of safety data by independent committees, and international regulators. The UK committee has concluded its investigations and recommended to the MHRA that trials in the UK are safe to resume.

University of Oxford potential COVID-19 vaccine Phase III clinical trial initiated in the US - Development of the potential COVID-19 vaccine has expanded into a Phase III clinical trial in the US to assess the safety, efficacy and immunogenicity of the potential vaccine for the prevention of COVID-19. The trial is funded by US Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, and led by AstraZeneca. The NIAID-supported COVID-19 Prevention Network (CoVPN) will participate in the trial.

Available at: https://clinicaltrials.gov/ct2/show/NCT04516746?term=NCT04516746&draw=2&rank=1

see also: Development of COVID-19 vaccine AZD1222 expands into US Phase III clinical trial across all adult age groups

D8110C00001 is a Phase III randomised, double-blind, placebo-controlled multicentre study assessing the safety, efficacy, and immunogenicity of AZD1222 compared to placebo for the prevention of COVID-19, in up to 30,000 participants across approximately 100 trial centres in and outside the US. Trial participants aged 18 years or over who are healthy or have medically stable chronic diseases, and are at increased risk for being exposed to the SARS-CoV-2 virus and COVID-19 will be randomised in a 2:1 ratio to receive two intramuscular doses of either 5 x10¹⁰ viral particles of AZD1222 or saline placebo four weeks apart, on day one and 29. Randomisation will be stratified by age (≥ 18 to < 65 years, and ≥ 65 years), with at least 25% of participants to be enrolled in the older age range. Individuals interested in participating in the Phase III D8110C00001 vaccine trial can visit https://www.c19vaccinestudy.com or www.CoVPN.org websites for more information.

Researching antibodies to target COVID-19 - More than 50 virology, protein engineering, clinical and bioprocess experts across BioPharmaceuticals R&D and Operations are working on this effort, using proprietary antibody discovery technology that was previously developed under an agreement with the US Defense Advanced Research Projects Agency (DARPA) as part of the Pandemic Preparedness Platform program. As part of the DARPA program, the technology enabled AstraZeneca scientists to rapidly discover potential therapeutic antibodies for influenza-A in less than 60 days. The Chinese Academy of Sciences (China) and Vanderbilt University Medical Center (US) are providing AstraZeneca with genetic sequences for antibodies they have discovered against SARS2-CoV-2 for further in silico and in vitro assessment.

Bausch Health Initiates VIRAZOLE® (Ribavirin for Inhalation Solution, USP) Clinical Study in Patients with COVID-19 - a clinical trial program in Canada evaluating an investigational use of VIRAZOLE® (Ribavirin for Inhalation Solution, USP) in combination with standard of care therapy to treat hospitalized adult patients with respiratory distress due to COVID-19. Because ribavirin is a synthetic nucleoside that works to stop viral replication, VIRAZOLE may be effective in reducing the severity of COVID-19 infection. VIRAZOLE is currently approved in several countries around the world, including the United States and Canada, for the treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus (RSV).

Study to Evaluate the Safety and Efficacy of VIRAZOLE® in Hospitalized Adult Participants With Respiratory Distress Due to COVID-19

BioCryst Pharmaceuticals is developing its drug galidesivir as a potential treatment for more than 20 RNA viruses. But SARS-CoV-2, the virus that causes COVID-19, will no longer be one of them. 

The Durham company has reported early stage clinical trial results showing that treatment with the experimental antiviral offered COVID-19 patients no benefit compared to a placebo. The study wasn’t designed to demonstrate clinical efficacy, and small Phase 1 clinical trials typically enroll healthy volunteers to assess a drug’s safety before testing the drug on sick patients. Galidesivir achieved the safety measure with no serious problems associated with the drug. 

Nevertheless, the BioCryst study, funded by the National Institute of Allergy and Infectious Diseases (NIAID), failed to provide signs that the drug could treat COVID-19 infection. 

Galidesivir is an investigational broad-spectrum antiviral drug that was safe and well tolerated in previously reported Phase 1 trials in healthy subjects. Galidesivir has demonstrated broad-spectrum activity in vitro against more than 20 RNA viruses in nine different families, including the coronaviruses that cause MERS and SARS.

Celularity Announces FDA Clearance of IND Application for CYNK-001 in Coronavirus, First in Cellular Therapy - Celularity Inc., a clinical-stage company developing allogeneic cellular therapies from human placentas, has announced that the U.S. Food and Drug Administration (FDA) has cleared the Company's Investigational New Drug (IND) application for the use of its proprietary CYNK-001 in adults with COVID-19. With this, Celularity will commence a Phase I/II clinical study including up to 86 patients with COVID-19. 

Other companies mentioned: Sorrento Therapeutics, United Therapeutics/Lung Biotechnology

CytoDyn’s Phase 2 Study of Leronlimab for Mild-to-Moderate COVID-19 Selected for Oral Presentation at the Special isirv-AVG Virtual Conference on ‘Therapeutics for COVID-19’ -  An oral presentation was given at the Special isirv-Antiviral Group Conference on ‘Therapeutics for COVID-19.’ Additional details can be found on the conference web site here. 

see also: https://www.clinicaltrials.gov/ct2/show/NCT04347239?term=leronlimab&cond=Covid19&draw=2&rank=2 for late onset intervention therapies 

Novant Health Initiates Phase 2 COVID-19 Trial with CytoDyn’s Leronlimab - Novant Health is initiating patient enrollment in CytoDyn’s Phase 2 randomized clinical trial for COVID-19 patients with mild-to-moderate indications.  Novant Health is the first site in the southeastern United States to initiate this Phase 2 trial and the second clinical trial site in the nation.

Treatment with CytoDyn's Leronlimab Indicates Significant Trend Toward Immunological Restoration in Severely Ill COVID-19 Patients - Patient test data reveals improvement in cytokines, IL-6, and a trend toward the normalization of the CD4/CD8 ratio.

Leronlimab Used in Seven Patients with Severe COVID-19 Demonstrated Promise with Two Intubated Patients in ICU, Removed from ICU and Extubated with Reduced Pulmonary Inflammation

CytoDyn Reached Its Enrollment Target for Phase 2 COVID-19 Trial for Mild to Moderate Indication – Primary End Point Announcement Is Next - CytoDyn has met its 75-patient enrollment target in its Phase 2 clinical trial for COVID-19, a randomized clinical trial for mild-to-moderate COVID-19 population in the U.S. and enrollment continues in its Phase 2b/3 randomized clinical trial for severe and critically ill COVID-19 population in several hospitals throughout the country.

Available Therapies via Single-Patient EA

A Compassionate Use Study of Leronlimab in Breast Cancer

Eiger BioPharmaceuticals Announces First COVID-19 Patients Dosed with Peginterferon Lambda - Approximately 120 patients with mild COVID-19 at the Stanford University School of Medicine will be randomized 1:1 to a single subcutaneous dose of Lambda or normal saline placebo to evaluate the efficacy of Lambda in reducing the duration of viral shedding of SARS-CoV-2 virus and in reducing duration of symptoms and hospitalization in patients with mild COVID-19.  Patients will be followed for 28 days.

Available Therapies via Single-Patient EA

• Lonafarnib
• Pegylated Interferon Lambda
• Avexitide

Disease/Category-Specific EA Policies/Criteria

The Hutchinson-Gilford Progeria Syndrome and Progeroid Laminopathy Managed Access Program

Eiger BioPharmaceuticals, the distributor of the drug lonafarnib, is sponsoring a Managed Access Program (MAP) for eligible patients with Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) or a Progeroid Laminopathy (PL).  The protocol governing this program can be viewed at ClinicalTrials.gov. The MAP study number is NCT03895528.  Clinigen is the administrator of the lonafarnib MAP for HGPS and PL.

Patients or family members desiring more information about this program should speak to their doctors  or contact The Progeria Research Foundation at 978-535-2594 or e-mail info@progeriaresearch.org.  Patients and family members should not contact Clinigen.  Clinigen is only authorized to speak with doctors.

For treating doctors with questions about the MAP, please contact Clinigen’s Medicine Access Team at +44 (0) 1932 824123 or email medicineaccess@clinigengroup.com.  The doctor may also e-mail Eiger at ProgeriaMA@eigerbio.com or Eigeraccess@eigerbio.com.

Lilly Announces Proof of Concept Data for Neutralizing Antibody LY-CoV555 in the COVID-19 Outpatient Setting - Lilly announced proof of concept data from an interim analysis of the BLAZE-1 clinical trial, showing a reduced rate of hospitalization for patients treated with LY-CoV555. The randomized, double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555, a SARS-CoV-2 neutralizing antibody, for the treatment of symptomatic COVID-19 in the outpatient setting. The trial enrolled mild-to-moderate recently diagnosed COVID-19 patients across four groups (placebo, 700 mg, 2800 mg, and 7000 mg).

see: https://clinicaltrials.gov/ct2/results?cond=&term=nct04497987&cntry=&state=&city=&dist= 

Lilly's Neutralizing Antibodies and COVID-19 Fact Sheet 

Baricitinib in Combination with Remdesivir Reduces Time to Recovery in Hospitalized Patients with COVID-19 in NIAID-Sponsored ACTT-2 Trial - Lilly announced initial data emerging from the Adaptive COVID-19 Treatment Trial (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). ACTT-2 included more than 1,000 patients and began on May 8 to assess the efficacy and safety of a 4-mg dose of baricitinib plus remdesivir versus remdesivir in hospitalized patients with COVID-19. Baricitinib in combination with remdesivir met the primary endpoint of reduction of time to recovery in comparison with remdesivir.

Eli Lilly and Company announced it has entered into an agreement with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to study Olumiant (baricitinib) as an arm in NIAID's Adaptive COVID-19 Treatment Trial. Baricitinib, an oral JAK1/JAK2 inhibitor marketed as OLUMIANT^®, is approved in more than 65 countries as a treatment for adults with moderately to severely active rheumatoid arthritis. Given the inflammatory cascade seen in COVID-19, baricitinib's anti-inflammatory activity has been hypothesized to have a potential beneficial effect in COVID-19 and warrants further study in patients with this infection. https://investor.lilly.com/news-releases/news-release-details/lilly-begins-clinical-testing-therapies-covid-19

see also: https://clinicaltrials.gov/ct2/results?cond=COVID+OR+SARS+OR+MERS+OR+CORONAVIRUS&term=baricitinib&strd_s=01%2F01%2F2020&strd_e=&cntry=&state=&city=&dist=&Search=Search&recrs=a&recrs=b&recrs=c&recrs=d&recrs=f&recrs=k

AbCellera and Lilly to Co-develop Antibody Therapies for the Treatment of COVID-19 - AbCellera and Lilly will select from 500+ unique antibodies isolated from one of the first U.S. patients who recovered from COVID-19 to create antibody therapeutics for treatment and prevention of COVID-19

Fujifilm announces the start of a phase III clinical trial of influenza antiviral drug “Avigan Tablet” on COVID-19 and commits to increasing production

For more information: https://www.fujifilm.com/jp/en/news/hq/3211?_ga=2.116910662.1504568395.1585764405-146260470.1585764405

Information of Avigan Tablet in relation to COVID-19 

Avigan Tablet was approved for manufacture and sale in Japan in 2014 as an influenza antiviral drug. The drug is to be considered for use only when there is an outbreak of novel or re-emerging influenza virus infections in which other influenza antiviral drugs are either not effective or insufficiently effective, and the Japanese government decides to use the drug as a countermeasure against such influenza viruses. Thus, while the Japanese government has a certain stockpile of the drug, Avigan Tablet has never been distributed in the market and is not available at hospitals and pharmacies in Japan or overseas.

Favipiravir, the active pharmaceutical ingredient of Avigan Tablet, has a mechanism of action that prevents the propagation of viruses. The drug may potentially have an antiviral effect on the novel coronavirus as it is classified into the same type (single-stranded RNA virus) as influenza virus. However, at this stage, clinical application of Avigan Tablet to treat Coronavirus disease (Covid-19) is under study and preparation in order to obtain clear evidence of the drug's efficacy and safety.

Avigan Tablet has not been approved for marketing in any countries other than Japan. If any other national government or regulatory authority decides the use of Avigan Tablet, Fujifilm group intends to cooperate sincerely with the supply of Avigan Tablet to such countries in consultation and coordination with the Japanese government.

Marketed as Favilavir by  Zhejiang Hisun Pharmaceuticals (China)

Fulcrum Therapeutics Announces Initiation of Multi-Center Phase 3 (LOSVID) Trial with Losmapimod for Hospitalized COVID-19 Patients - The LOSVID trial is a Phase 3, international, multicenter trial designed to assess the safety and efficacy of a 15 mg twice per day oral dose of losmapimod compared to placebo for 14 days on top of standard of care in approximately 400 patients hospitalized with COVID-19 and at risk of progression to critical illness based on older age and elevated systemic inflammation. 

For more information, email clinicaltrials@fulcrumtx.com.

COVID-19 Resource Page

Expanded Access Treatment Protocol: Remdesivir (RDV; GS-5734) for the Treatment of SARS-CoV2 (CoV) Infection

Expanded Access Remdesivir (RDV; GS-5734™) - for DOD/military personnel only

Emergency Access to Remdesivir Outside of Clinical Trials

Remdesivir Clinical Trials

An Open Letter from our Chairman and CEO (March 28, 2020)

An Update on COVID-19 from our Chairman & CEO (April 4, 2020)

"Gilead is providing the entirety of this existing supply at no cost, to treat patients with the most severe symptoms of COVID-19. The 1.5 million individual doses are available for compassionate use, expanded access and clinical trials and will be donated for broader distribution following any potential future regulatory authorizations." 

Disease/Category-Specific EA Policies/Criteria

Emergency Access to Remdesivir Outside of Clinical Trials

Expanded Access Treatment Protocol: Remdesivir (RDV; GS-5734) for the Treatment of SARS-CoV2 (CoV) Infection

Expanded Access Remdesivir (RDV; GS-5734™) - for DOD/military personnel only

Remdesivir Clinical Trials

GSK COVID-19 vaccine development collaboration with Clover Biopharmaceuticals begins clinical trials - Clover Biopharmaceuticals initiates phase 1 study using GSK pandemic adjuvant in combination with COVID-19 vaccine candidate SCB-2019. Preliminary safety and immunogenicity results for the Phase 1 study are expected in August 2020. In parallel, the planning for a global Phase 2b/3 vaccine efficacy trial has begun, with initiation targeted later in 2020.

Sanofi and GSK to join forces in unprecedented vaccine collaboration to fight COVID-19 - Sanofi will contribute its S-protein COVID-19 antigen, which is based on recombinant DNA technology. GSK will contribute its proven pandemic adjuvant technology to the collaboration. 

GSK and Vir Biotechnology enter collaboration to find coronavirus solutions - We have announced a collaboration with Vir Biotechnology to use Vir’s monoclonal antibody platform technology to accelerate existing and identify new anti-viral antibodies that could be used as therapeutic or preventative options for COVID-19. Subject to regulatory review, the companies plan to proceed directly into a phase 2 clinical trial within the next three to five months. 

Through the COVID-19 Therapeutics Accelerator, GSK will make available compounds from its libraries for screening for activity against COVID-19.

Single-Patient EA Policies/Criteria

http://www.gsk.com/media/3368/compassionate-use.pdf

Go to GSK Compassionate Use Request Portal at https://gsk-cu-portal.idea-point.com/ to make a request.

Grifols completes development of very high sensitivity molecular test to detect SARS-CoV-2 virus - a specific TMA (Transcription-Mediated Amplification) molecular test that permits the detection of the SARS-CoV-2 virus in plasma, blood and respiratory samples.

Grifols Announces Formal Collaboration with US Government to Produce the First Treatment Specifically Targeting COVID-19 - Grifols will collect plasma from convalescent COVID-19 patients, process this specific plasma into a hyperimmune globulin and support the necessary preclinical and clinical studies to determine if anti-SARS-CoV-2 hyperimmune globulin therapy can successfully be used to treat COVID-19 disease. This initiative is a result of a collaboration between Grifols, the U.S. Food and Drug Administration (FDA), the U.S. Biomedical Advanced Research Authority (BARDA), and other Federal health agencies.

People Who Have Recovered from COVID-19 Can Now Donate their Convalescent Plasma in select Grifols U.S. Plasma Donor Centers - Grifols has begun identifying, screening and selecting volunteer donors who have recovered from COVID-19 to donate their plasma in select U.S. cities. The plasma will be used to produce a hyperimmune globulin that, if proven effective, could potentially treat the disease.

Innovation has received inquiries asking about Brilacidin’s potential to treat the coronavirus (COVID-19) given the urgent worldwide need to find effective treatments for this deadly epidemic.

For more information, contact:  covid19@ipharminc.com

The linked PDF (click here), updated on March 1, is an informational overview summarizing the scientific rationale for Brilacidin as a potential coronavirus (COVID-19) treatment. Brilacidin, and other defensin-mimetics similar in structure, have been tested against various clinical isolates of both gram-positive and gram-negative pathogens, with strong activity exhibited across multiple isolates. Enveloped viruses, like the coronavirus, have also been tested, with activity noted. University of Pennsylvania scientists who conducted early Brilacidin research are optimistic about the multi-tiered advantages of Brilacidin to elicit a response, particularly when accompanied by drug optimization, formulation and delivery work, which is supported in the academic literature.

Laurent Pharmaceuticals Joins Battle Against COVID-19 - The company is planning to test its lead drug LAU-7b in patients with COVID-19 disease, as part of a Phase 2 clinical trial. LAU-7b is a novel once-a-day oral form of fenretinide, an investigational drug under development by Laurent Pharmaceuticals for its ability to help control inflammation in the lungs.  Laurent is working closely with regulatory authorities in Canada and United States, planning to initiate a randomized, placebo-controlled Phase II clinical study, within a month. The study will involve approximatively 200 patients diagnosed with COVID-19 and at risk to develop lung complications, for a treatment duration of 14 days.

Read more about developing therapeutics and vaccines for coronaviruses 

NIAID has also supported the clinical testing of two promising antibody-based therapeutics, which prevent the virus from infecting and entering cells.  NIAID conducted a phase 1 clinical trial of  SAB-301, an experimental MERS treatment developed from cattle that make human antibodies.  This was shown to be safe and well tolerated in healthy adults. More recently, NIAID supported a Phase I clinical trial of a combination of two monoclonal antibodies, REGN3048 and REGN 3051, and demonstrated this combination was also safe and well tolerated.  Planning for follow on Phase 2/3 efficacy studies using SAB-301 is currently ongoing with partners where MERS is endemic, including the Kingdom of Saudi Arabia.

NIH clinical trial of investigational vaccine for COVID-19 begins

Disease/Category-Specific EA Policies/Criteria

Developing Therapeutics and Vaccines for Coronaviruses

https://www.niaid.nih.gov/diseases-conditions/coronaviruses-therapeutics-vaccines

NIAID has also supported the clinical testing of two promising antibody-based therapeutics, which prevent the virus from infecting and entering cells.  NIAID conducted a phase 1 clinical trial of  SAB-301, an experimental MERS treatment developed from cattle that make human antibodies.  This was shown to be safe and well tolerated in healthy adults. More recently, NIAID supported a Phase I clinical trial of a combination of two monoclonal antibodies, REGN3048 and REGN 3051, and demonstrated this combination was also safe and well tolerated.  Planning for follow on Phase 2/3 efficacy studies using SAB-301 is currently ongoing with partners where MERS is endemic, including the Kingdom of Saudi Arabia.

NIH clinical trial of investigational vaccine for COVID-19 begins

https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins

Pfizer and BioNTech to Co-Develop Potential COVID-19 Vaccine - Companies will jointly develop BioNTech’s mRNA-based vaccine candidate BNT162 to prevent COVID-19 infection Collaboration aims to accelerate global development of BNT162, leveraging expertise and resources of both companies Builds on 2018 agreement to jointly develop an mRNA-based influenza vaccine. See also: Racing to Develop a Potential COVID-19 Vaccine with Unprecedented Partnership 

Pfizer Shares Safety Data on Azithromycin-Hydroxychloroquine Combination - Recently, a group of French researchers disclosed results of an independent study in France exploring the use of hydroxychloroquine in 20 patients for the potential treatment of COVID-19 diseasei . Among those 20 patients, six also received Pfizer’s product, azithromycin (Zithromax®). In that study, the proportion of patients with virologic cure after 6 days (as indicated by negative PCR tests) was higher in the 20 patients who received hydroxychloroquine as compared to the 16 controls. The highest rate of cure was seen in those that also received azithromycin—all six of those patients achieved virologic cure. In light of these preliminary findings, and as Pfizer interprets the data in the context of previous research into other infectious diseases, the company would like to share additional information that may facilitate the further exploration of this combination.

Pfizer Outlines Five-Point Plan to Battle COVID-19

Single-Patient EA Policies/Criteria

www.pfizercares.com

PharmaMar has submitted a Phase II clinical trial of Aplidin® (plitidepsin) for the treatment of COVID-19 to the Spanish Medicines Agency - The objective of the trial is to evaluate the efficacy and safety of plitidepsin as a treatment for COVID-19 (SARS-CoV-2) in hospitalized patients. Plitidepsin, which is approved in Australia for the treatment of multiple myeloma, has also demonstrated efficacy as an antiviral in in vitro studies conducted at the Spanish CSIC's National Biotechnology Center against the human coronavirus HCoV-229E, and previously against other types of virus at the Carlos III Health Institute.

PharmaMar reports positive results for Aplidin® against coronavirus HCoV-229E

Available Therapies via Single-Patient EA

There is an Expanded Access Program (EAP) for lurbinectedin to treat patients in the United States (U.S.) with relapsed Small Cell Lung Cancer (SCLC), who are unable to enter clinical trials and there are no appropriate alternative treatments.

Healthcare professionals wishing to request access to lurbinectedin under the EAP or who would like to find out more should do so by emailing Lurbinectedin.EAP@Bionical-Emas.com.

See also A Multicenter Expanded Access Treatment Protocol of Lurbinectedin in Previously Treated SCLC in the USA

Pulmotect’s PUL-042 Shows Promising Pre-Clinical Efficacy in Preventing Lethal Coronavirus Infection - Experiments conducted at the University of Texas Medical Branch at Galveston (UTMB) show pre-clinical efficacy in mice protecting against both the lethal SARS-associated coronavirus (SARS-CoV) and the MERS-associated coronavirus (MERS-CoV). In mouse models, a single inhaled dose of PUL-042 was shown to protect the host from SARS-CoV, and the drug significantly reduced the amount of virus in the lungs after infection with either the SARS-CoV or MERS-CoV viruses.

The Use PUL-042 Inhalation Solution to Prevent COVID-19 in Adults Exposed to SARS-CoV-2

The Use of PUL-042 Inhalation Solution to Reduce the Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection

Opaganib - COVID-19 - RedHill is working to develop opaganib (Yeliva, ACB294640) for COVID-19. Opaganib has a unique mechanism of action, with both anti-inflammatory and anti-viral activity, targeting a critical host factor, which minimizes the potential development of resistance due to viral mutations. RedHill is advancing a development program evaluating opaganib as a therapy for patients with severe COVID-19 infection, which includes two ongoing clinical studies:

• A global randomized, double-blind, parallel-arm, placebo-controlled global Phase 2/3 study (NCT04467840)
   
• A U.S. randomized, double-blind, placebo-controlled Phase 2 study (NCT04414618)

RedHill Biopharma’s Phase 2/3 COVID-19 Study Approved in Mexico - The global Phase 2/3 study with opaganib is set to enroll up to 270 patients with severe COVID-19 across 40 clinical site. The global Phase 2/3 study has been approved in Mexico, the UK and Russia and is also under review in Italy, Brazil and additional countries. Enrollment in a parallel U.S. Phase 2 study in patients with severe COVID-19 is approximately 50% complete and is expected to be completed this month. Potential submission of global emergency use applications planned as early as Q4/2020.

RedHill Biopharma Announces Approval of Compassionate Use of Opaganib for COVID-19 in Italy  

RedHill Announces First COVID-19 Patient Treated with Opaganib in Israel Under Compassionate Use 

Available Therapies via Single-Patient EA

COVID-19 - Yeliva (opaganib)

Expanded Access for the Treatment of Advanced Cholangiocarcinoma With ABC294640 (Yeliva ®)

Ridgeback Biotherapeutics Announces MHRA Clearance to Begin Human Testing of EIDD-2801 in the UK for COVID-19 and the Start of Phase 1 - This action by the MHRA allowed Ridgeback to commence Phase 1 in the UK on Friday April 10^th. EIDD-2801 is a direct acting anti-viral nucleoside analogue.  Essentially, EIDD-2801 tricks RNA viruses into including the wrong building blocks as it tries to reproduce itself.  This leads to dramatically reduced levels of virus in animals infected with a wide variety of RNA viruses when treated with EIDD-2801.  EIDD-2801 has been shown to treat MERS and SARS (two severe coronavirus infections) in animals when given after an infection has been established.  When given prophylactically EIDD-2801 is able to prevent significant manifestations of disease in animals challenged with MERS and SARS.    

FDA Clears the Way for Ridgeback Biotherapeutics to begin Human Testing of a Promising Potential Treatment for COVID-19 - The U.S. Food and Drug Administration (FDA) has approved an Investigational New Drug application by Drug Innovation Ventures at Emory (DRIVE), LLC, wholly owned by Emory University, for an orally available antiviral compound, EIDD-2801, exclusively licensed to Ridgeback Biotherapeutics.  This action by the FDA allows Ridgeback to initiate human clinical testing of EIDD-2801 in the United States. EIDD-2801 prevents the replication of SARS-CoV-2, the virus that causes COVID-19, and has shown potent activity against SARS-CoV and MERS-CoV in animal models of infection. In addition to coronaviruses, EIDD-2801 has broad spectrum activity against a number of diseases of public health concern, including influenza, chikungunya, Ebola, and equine encephalitis (VEE and EEE). The antiviral is orally available and, in addition to COVID-19, is being developed for the treatment of seasonal and pandemic influenza under a contract awarded to Emory Institute for Drug Development by the National Institute of Allergy and Infectious Diseases (NIAID) and for Venezuelan and Eastern equine encephalitis virus (VEEV and EEEV) by the Defense Threat Reduction Agency (DTRA). 

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mAb114 is currently under study in the Democratic Republic of the Congo through an Expanded Access Protocol administered as part of the Monitored Emergency Use of Unregistered and Investigational Interventions for Ebola virus disease (MEURI).

On the 18th March Synairgen announced that it has received expedited approvals from the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) and Health Research Authority (HRA) to conduct a trial of SNG001 in COVID-19 patients. Synairgen is developing a formulation of IFN-beta, called SNG001, for direct delivery to the lungs via nebulisation, to treat and/or prevent LRT illness caused by respiratory viruses. Synairgen’s Phase II trial in COVID-19 patients, called SG016 (EudraCT: 2020-001023-14), is a double-blind, placebo-controlled trial. Initially, the pilot phase of the study involving 100 COVID-19 patients, is taking place across a number of NHS trusts in the United Kingdom.

https://www.synairgen.com/covid-19/

Commencement of dosing in COVID-19 trial

Synairgen to start trial of SNG001 in COVID-19 imminently

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On the 18^th March Synairgen announced its plans to initiate a pilot clinical trial of SNG001 in COVID-19 patients. The trial will provide data on the efficacy of inhaled interferon beta in the treatment of ambulatory and hospitalised patients infected with SARS-CoV-2. Since the announcement, we have received a number of requests for SNG001 supplies to treat individuals outside the trial. As SNG001 is an experimental drug, untested as to safety and efficacy in this patient group, we regret that we are unable to fulfil any such request at this time. Synairgen’s team is working very hard to establish these measures in a well-controlled environment as quickly as possible. https://www.synairgen.com/

Takeda Initiates Development of a Plasma-Derived Therapy for COVID-19 - Takeda is initiating the development of an anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) to treat high-risk individuals with COVID-19. Hyperimmune globulins are plasma derived-therapies that have previously been shown to be effective in the treatment of severe acute viral respiratory infections and may be a treatment option for COVID-19. 

This research requires access to source plasma from people who have successfully recovered from COVID-19 or who have been vaccinated, once a vaccine is developed. These convalescent donors have developed antibodies to the virus that could potentially mitigate severity of illness in COVID-19 patients and possibly prevent it. BioLife Plasma Services, part of Takeda, has implemented a protocol for collecting plasma from healthy individuals who have recovered from COVID-19 to enable development of a potential therapy for COVID-19, made from human plasma. For more information, go to https://pub.s1.exacttarget.com/3xhgrthonqe?_ga=2.157390458.1771561704.1585853136-1731863841.1585853136

Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune Therapy - Other companies involved in this alliance include CSL Behring, Octapharma, and Biotest AG

CoVIg-19 Plasma Alliance Builds Strong Momentum Through Expanded Membership and Clinical Trial Collaboration

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EXPANDED ACCESS TO INVESTIGATIONAL DRUGS

https://www.takedaoncology.com/medicines/expanded-access-to-investigational-drugs/

Join Us In The Fight Against The Coronavirus! Vir Biotechnology is conducting a research study for COVID-19 patients who have recovered from this infection. Consider donating your blood to help researchers better understand this virus. Email at virus@vir.bio or visit https://www.vir.bio/virus/

GSK and Vir Submit Emergency Use Authorization Application to FDA for Intramuscular Administration of Sotrovimab for the Early Treatment of COVID-19 - GlaxoSmithKline plc and Vir Biotechnology, Inc. announced the submission of an application to the FDA requesting an amendment to the Emergency Use Authorization (EUA) for sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, to include intramuscular (IM) administration. The EUA for sotrovimab was granted by the FDA in May 2021 as an investigational single-dose intravenous (IV) (500 mg) infusion SARS-CoV-2 monoclonal antibody for the early treatment of COVID-19, and the companies are requesting an expansion to the EUA to also include IM administration (500 mg).

GSK and Vir Biotechnology Announce United States Government Agreement to Purchase Additional Supply of Sotrovimab, Authorized for the Early Treatment of COVID-19 - The US government will purchase an additional 600,000 doses of sotrovimab, an investigational monoclonal antibody for the early treatment of COVID-19, enabling further nationwide access to sotrovimab for patients. The additional 600,000 doses will be delivered throughout the first quarter of 2022. This agreement is an amendment to earlier commitments announced with the US government in November 2021. Preclinical data generated through both pseudo-virus and live virus testing demonstrate sotrovimab retains activity against all tested SARS-CoV-2 variants of concern including Delta and Omicron.

Vir Biotechnology Announces New Research Describing the Structural Basis of SARS-CoV-2 Omicron Immune Evasion and Receptor Engagement - New preclinical research published to the preprint server bioRxiv, describing the structural basis and magnitude by which the new SARS-CoV-2 Omicron variant (B.1.1.529) evades antibody mediated immunity, as well as its enhanced ability to bind to the human ACE-2 receptor. Data define the specific Omicron mutations and their detrimental impact on the binding of the majority of tested monoclonal antibody (mAbs) therapies that target the receptor binding motif of the spike protein, a region that is more prone to mutate. Further, these data add to the growing body of evidence from recent pseudo- and live virus neutralization findings demonstrating that sotrovimab retains activity against the Omicron variant, as well as all tested variants of concern. This study was conducted in close collaboration with David Veesler, Ph.D., Associate Professor of Biochemistry, University of Washington & Investigator, Howard Hughes Medical Institute, and members of his laboratory. Sotrovimab is an investigational SARS-CoV-2 neutralizing monoclonal antibody developed in partnership with GlaxoSmithKline for the early treatment of COVID-19.

Vir and Alnylam Expand Collaboration to Advance Investigational RNAi Therapeutics Targeting Host Factors for the Treatment of COVID-19 - This expansion includes up to three additional targets focused on host factors for SARS-CoV-2, including ACE2 and TMPRSS2, both of which are considered critical for viral entry, with the potential for an additional host target to emerge from Vir’s functional genomics work.

GSK and Vir Biotechnology enter collaboration to find coronavirus solutions - Promising antibody candidates for SARS-CoV-2 to be accelerated into phase 2 clinical trials within the next three to five months

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