The Covid-19 Pandemic and Haemoglobin Disorders: Vaccinations & Therapeutic Drugs
The Covid-19 Pandemic and Haemoglobin Disorders: Vaccinations & Therapeutic Drugs
The Covid-19 Pandemic and Haemoglobin Disorders: Vaccinations & Therapeutic Drugs
AND HAEMOGLOBIN
DISORDERS
VACCINATIONS &
THERAPEUTIC
DRUGS
An Informational Guide
from the
Thalassaemia
International Federation
(TIF)
Prepared by:
Dr Androulla Eleftheriou,
Executive Director, TIF
Last Updated:
12 May 2020
VACCINATIONS & THERAPEUTIC DRUGS
Introduction
The viral genome was mapped very soon as rom early January 2020 and shared globally.
In February 2020, the WHO published an overview of the potential therapeutic candidates
for the treatment of COVID-19. The document outlines 76 regimens that have been
proposed (as of February 17, 2020) for the treatment of patients infected with the virus.
Thirty-eight of these candidates are in the preclinical state with minimal information
available on their proposed mechanism, uses, doses routes, or planned trials. Sixteen of
the remaining regimens contain an interferon-based product. The rest include a variety of
antimicrobials, corticosteroids, convalescent plasma, and biologics.
The Director-General of the WHO, Mr Tedros Adhanom, stated on the 10th of April 2020,
that more than 70 countries have joined WHO’s trial to accelerate research on effective
treatments and 20 Institutions and companies ‘are racing to develop a vaccine’. The
Director-General will be soon announcing an initiative for the accelerated development
and equitable distribution of vaccines.
Vaccines
An international randomised trial of candidate vaccines against COVID-19, 19th April 2020
The trial will rapidly enroll and individually randomize very large numbers of adult
participants in many different populations. Each participant will be contacted weekly for
information as to whether any potentially relevant symptoms have arisen, with laboratory
testing triggered if the report suggests COVID-19. By using a shared placebo/control group
and a common Core protocol to evaluate multiple candidate vaccines in the trial, resources
allocated to the evaluation of each candidate vaccine are judiciously saved while a high
standard of scientific rigor and efficiency is ensured.
The trial is powered to provide sufficient evidence of safety and vaccine efficacy against
COVID-19 to support decision-making about global vaccine.
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Many of these are included in the 60 studies listed in ClinicalTrials.gov whose descriptions
include the term COVID-19, as well as the 7 studies whose descriptions include SARS-
CoV-2. The U.S. website lists 331,715 trials in 209 countries.
China published Guidelines for clinical studies of drugs and vaccines intended to combat
the deadly viral outbreak giving priority to drugs already marketed and whose efficacy has
been proven in animal and in vitro studies.
In all the above studies and programmes, considerable effort is placed on repurposing
existing drugs and assessing their effectiveness and safety in addressing COVID-19 while
at the same time there is a plethora of drug developers, as seen in GEN’s A-List of top 35
treatments under development and/or clinical study for COVID-19.
Τhere are 412 published articles in the PubMed (a free full-text archive of biomedical and
life sciences journal) and 312 clinical trials recruited at clinicaltrials.gov for 2020. “A global
war of pharmaceutical industry and countries” with interest of over 1 trillion dollars always
declaring of course “no conflict of interest”.
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Earlier this month Microsoft founder and billionaire philanthropist Bill Gates issued an
urgent call for world leaders to unite and start planning how vaccines will be manufactured
and distributed now, to avoid a potentially deadly delay in delivering the treatment further
down the line.
“We aren’t sure which vaccines will be the most effective yet, and each requires unique
technology to make,” he said.
“That means nations need to invest in many different kinds of manufacturing facilities now,
knowing that some will never be used. Otherwise, we’ll waste months after the lab
develops an immunization, waiting for the right manufacturer to scale up.”
The COVID-19 pandemic represents the greatest global public health crisis of this
generation and, potentially, since the pandemic influenza outbreak of 1918. The speed
and volume of clinical trials launched to investigate potential therapies for COVID-19
highlight both the need and capability to produce high-quality evidence even in the middle
of a pandemic.
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Candidate Vaccinations and Therapeutic Drugs
Below is a catalogue of the prospective vaccinations and therapeutic drugs listed by their
developer and a short description.
VACCINATIONS
New England Journal of Medicine - Perspective, Developing Covid-19 Vaccines at Pandemic Speed
VACCINATIONS & THERAPEUTIC DRUGS
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1. AJ Vaccines
AJ Vaccines has launched the development of a vaccine against COVID-19. The company
will use the latest technology to develop antigens that can mimic the native structures of
the virus. The vaccine will be capable of inducing a strong immune response in the body
thereby protecting against the infection. As of the beginning of May the development is
still at a preclinical stage.
2. Altimmune
Altimmune said February 28 that it completed the design and synthesis of the vaccine,
and was advancing it toward animal testing and manufacturing. Clinical testing of the
vaccine, it was announced could start in the third quarter. The company also said it was
“actively engaged in discussions with a number of potential partners.”
BNTX, -4.44% COVID-19 candidate vaccine, was developed by BioNTech and supported
by Pfizer. 360 patients in the U.S. had started to receive the first doses of the vaccine as
of May 5. Dosing in 200 participants in the German trial began April 23. The vaccine uses
a gene-based technology, messenger RNA, which has an advantage as it can move faster
into clinical trials
The first round of trial data are expected in May or June, with the vaccine candidate moving
into “expanded trials that could allow emergency use or accelerated approval coming in
the fall, possibly October.”
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The study is designed to evaluate the immunogenicity and safety of the Ad5-nCoV
vaccine—which encodes for a full-length spike (S) protein of SARS-CoV-2. The target is
to enrol 500 participants, with 250 of the subjects to receive a middle-dose vaccine group,
125 subjects to recieve a low-dose and 125 subjects in the placebo group. They will
investigate the immunogenicity at days 0, 14, 28 and 6 months after vaccination. Results
are not yet known.
The vaccine is being developed based on the trimeric s protein (S-TRIMER) of the COVID-
19 virus which is responsible for binding with the host cell causing a viral infection. Clover
scientists started designing the viral spike (S)-protein construct and completed its gene
synthesis. The vaccine has been produced in February in a mammalian cell culture. A
highly purified form is expected for pre-clinical studies.
6. CureVac
mRNA-based vaccine
CureVac and the public-private Coalition for Epidemic Preparedness Innovations (CEPI)
are collaborating to develop a vaccine against SARS-CoV-2, the partners said January
31, extending their existing partnership to develop a rapid-response vaccine platform.
CEPI has committed up to $8.3 million in additional funding for accelerated development,
manufacturing, and clinical tests. CEPI CEO Richard Hatchett said the Coalition and
CureVac aspire to bring the pathogen’s gene sequence to a vaccine candidate for clinical
testing “within a few months.”
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7. Generex Biotechnology
Generex said February 27 it has received a contract from the China Technology
Exchange, Beijing Zhonghua Investment Fund Management Co. Ltd., Biology Institute of
Shandong Academy of Sciences, and Sinotek-Advocates International Industry
Development (Shenzhen) Co. Ltd. to develop a Ii-key vaccine. Generex said it would
receive $1 million upfront to initiate project work in the U.S., a $5 million licensing fee for
the Ii-Key technology, payment by the Chinese consortium for all costs and expenses
related to the development of a COVID-19 vaccine, and a 20% royalty on each dose of
vaccine produced.
GSK agreed to provide Clover with its pandemic adjuvant system for further evaluation of
S-Trimer in preclinical studies, the companies said February 24, under a research
collaboration. GSK reasons that Clover could rapidly scale-up and produce large-
quantities of a new coronavirus vaccine since it has one of the largest in-house,
commercial-scale cGMP biomanufacturing capabilities in China.
8. Heat Biologics
Heat Biologics has announced plans to develop a vaccine to treat or prevent coronavirus
infection using its proprietary gp96 vaccine platform. The technology is capable of
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reprogramming live cells to produce antigens that can bind to the gp96 protein and
generate an immune response against those antigens. The company is finalizing
completion of the vaccine and plan to commence preclinical testing this spring.
The two companies on February 3 disclosed plans to develop and test the COVID-19
vaccine, combining the vaccine R&D experience (including work on the MERS-
coronavirus), in a rapid design of manufacturing processes for biopharmaceutical
production in plant-based expression systems. If successful, the research will deliver
product candidates for production at iBio’s FastPharming Manufacturing Facility, built in
2010 with funding from the Defense Advanced Research Projects Agency (DARPA), to
establish facilities capable of rapid delivery of medical countermeasures in response to a
disease pandemic.
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Researchers at the Imperial College have developed a candidate which, when injected,
will deliver the genetic instructions to muscle cells to make the SARS-CoV-2 spike surface
protein. This should provoke an immune response and create immunity to the virus.
The team, led by Professor Robin Shattock from Imperial's Department of Infectious
Disease, has been testing the candidate in animals since early February.
Clinical trials are expected to begin in June and the team will look to recruit healthy adults
to test the vaccine.
The vaccine was well-tolerated and demonstrated high immune responses, when
previously used against the MERS-CoV with high response in 94% of patients in the early-
stage clinical trial in July 2019. It also generated broad-based T cell responses in 88% of
the subjects.
The company stated pre-clinical testing for the SARS-CoV-2 virus. The development is
supported by a $9 million grant from the Coalition for Epidemic Preparedness Innovations
(CEPI). Also, the company has received a $5 million grant from the Bill & Melinda Gates
Foundation to accelerate the testing and development of the Cellectra® delivery device
for the intradermal delivery of INO-4800. Phase 1 trial has started this month (April), in 40
volunteers. INO-4800 Phase 2/3 U.S. clinical trial being prepared to start this summer,
according to a report from the company on 30th April. The company has entered into an
agreement to expand its manufacturing partnership with the German contract
manufacturer Richter-Helm BioLogics GmbH & Co. KG, to support large-scale
manufacturing of INOVIO's investigational DNA vaccine, with plans to produce one million
doses of INO-4800 by the end of 2020.
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Integral Molecular has launched a vaccine programme using its two technology platforms
including Shotgun Mutagenesis Epitope Mapping and the Membrane Proteome Array.
The technologies will help in understanding the human immune response to the
coronavirus and isolate the cellular receptors that enable the virus to spread quickly.
SARS-CoV-2 reporter virus particles are designed to be antigenically identical to wild-type
viruses but with a modified genome that expresses a convenient optical reporter gene
(GFP or luciferase) upon cellular infection.
The Shotgun technology helps in identifying more than 1,000 binding sites for antibodies,
while the Membrane Proteome Array technology is capable of identifying the receptors
through which viruses infect cells.
The company is providing access to free SARS-CoV-2 RVP trial samples to vaccine
developers to support COVID-19 research
An experimental vaccine is under development and human trials are expected to start in
September. On March 30, the company stated that it had identified a lead vaccine
candidate, and is scaling up its vaccine manufacturing capabilities aiming to put its lead
vaccine candidate in a Phase 1 clinical trial in September.
The PCR technology offers several advantages including high purity, increased production
speed, and absence of antibiotics and bacterial contaminants. Further, the vaccine gene
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developed through this technology can be effective without being inserted into the patient’s
genome.
The design for four DNA vaccine candidates is expected to be produced using the PCR
technology for carrying out animal testing. The design of one of the vaccine candidates is
based on the entire spike gene of the coronavirus, while the remaining are designed based
on the antigenic portions of the protein.
LineaRx, a majority-owned subsidiary of Applied DNA Sciences of Stony Brook, NY, and
Rome-based Takis Biotech said February 7 they have formed a joint venture to develop
the preclinical vaccine using PCR-based DNA manufacturing technology. No commercial
partner to take the coronavirus vaccine to market has been identified, the companies said.
16. Medicago
The company is developing a vaccine against SARS-CoV-2 and is partly funded by the
Canadian Institutes of Health Research (CIHR).
Medicago expects to initiate human trials by this summer (July/August 2020) with the
objective of completing the development program and submitting a dossier to authorities
by the end of next year (November 2021). The vaccine should be available after approval
from respective regulatory authorities.
A newly formed Israeli company working to develop a vaccine for the novel coronavirus
based on research by scientists at the Migal Galilee Research Institute secured $12 million
in an investment round led by Israeli crowdfunding venture investment platform OurCrowd.
The scientists had been working for four years to develop a vaccine against IBV (Infectious
Bronchitis Virus), which affects the respiratory tract, Avian coronavirus Infectious
Bronchitis Virus (IBV) vaccine. This vaccine has been modified to treat COVID-19. The
IBV vaccine was developed after 4 years of research and has high genetic similarity to the
human coronavirus. The Institute modified genetically the vaccine to treat COVID-19 and
will be available in the oral form. Migal believes that its proposed oral (mucosal)
vaccination technology can be ready for testing recently.
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The company is in talks with major strategic partners able to manufacture at high volume
and distribute globally.
Moderna said February 24 that it shipped the first batch of mRNA-1273 to the NIH’s
National Institute of Allergy and Infectious Diseases (NIAID) for use in a planned Phase I
study in the U.S. The primary aim of the Phase I open-label, dose-ranging trial study
(NCT04283461), which had yet to recruit patients at deadline, is to evaluate the safety and
reacto-genicity of a 2-dose vaccination schedule of mRNA-1273, given 28 days apart,
across 3 dosages in healthy adults. Moderna designed the vaccine in collaboration with
investigators at the NIAID Vaccine Research Center (VRC).
The first patient was dosed on March 16 and Phase I is still ongoing and is expected to
conclude in June 1. Participants will be followed for one year.
An unusual aspect is that this vaccine has NOT BEEN TESTED in laboratory animals as
is the rule. Phase 2 trials are expected to start this spring, since Moderna has received
the green light to initiate the trial. However, Moderna is pushing forward with
manufacturing the potential vaccine, as early as July, hoping that it proves safe for humans
and effective against the coronavirus.
19. Novavax
Phase 1 clinical trials are scheduled to start in mid-May. The first phase of the placebo-
controlled study will enrol 130 healthy adults and the first round of data from that study is
expected in July.
ChAdOx1 nCoV-19 vaccine. This is a more so-called platform technology which is used
to make vaccines against many different diseases.
The Oxford University, supported by the UK Ministry of Heath (announced April 21) has
already started clinical trials in humans in April 2020.
A £52.5 million funding has also been announced by the UK Health Secretary for anther
vaccine trial at London’s Imperial University due to begin in June.
The vaccine is an adenovirus vaccine vector (ChAdOx1) and was developed at Oxford’s
Jenner Institute. It has recently received further £20 million funding from the UK
Government almost all of it expected to be spent on the clinical trial development
programme. Prof Andrew Pollard, Chief Investigator, said that they expected to produce a
million doses as early as September (ahead of the 12-18 month timeline quoted by experts
around the world).
It was chosen as the most suitable vaccine for COVID-19 as it can generate a strong
immune response from one dose, but is not a replicating virus.
The Oxford University team's experimental product, called "ChAdOx1 nCoV-19", is a type
of immunisation known as a recombinant viral vector vaccine and is just one of at least 70
potential Covid-19 candidate shots under development by biotech and research teams
around the world.
The vaccine was chosen as the most suitable vaccine technology for the virus as it can
generate a strong immune response from one dose, said the team.
This means that the vaccine won’t cause an ongoing infection in the vaccinated person,
and also makes it safer to give to children, the elderly and anyone with a pre-existing
condition such as diabetes.
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1. Phase 1 will involve 510 healthy participants, aged 18 to 55, who will either receive
the ChAdOx1 nCoV-19 vaccine or a control injection for comparison. At the start of
the trial we will also recruit a separate small group of 10 volunteers who will receive
2 doses of ChAdOx1 nCoV-19 four weeks apart.
The MenACWY vaccine is being used as an ‘active control’ vaccine in this study,
to help us understand participants’ response to ChAdOx1 nCoV-19. The reason for
using this vaccine, rather than a saline control, is because we expect to see some
minor side effects from the ChAdOx1 nCOV-19 vaccine such as a sore arm,
headache and fever. Saline does not cause any of these side effects. If participants
were to receive only this vaccine or a saline control, and went on to develop side
effects, they would be aware that they had received the new vaccine. It is critical
for this study that participants remain blinded to whether or not they have received
the vaccine, as, if they knew, this could affect their health behaviour in the
community following vaccination, and may lead to a bias in the results of the study.
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2. If Phase 1 goes well, Phase 2 will then extend the maximum age of trial participants
to 55-70 years, then over 70.
3. Finally, Phase 3 will see 5,000 volunteers aged over 18 years tested, with half
receiving the COVID-19 vaccine.
The researchers explained: “Clear efficacy endpoints will be used to assess the
effectiveness of the vaccine, and volunteers from phase I and II will be included in the
follow-up.”
The researchers say they’re remaining cautious when mapping out a timeline for the trial,
however, scientists working on the vaccine have said they could know within six weeks,
from the onset of the clinical trial whether it will work.
They explained: “The best-case scenario is that by the autumn of 2020 we could have an
efficacy result from the phase III trial to show that the vaccine protects against the virus,
alongside the ability to manufacture large amounts of the vaccine, but these best-case
timeframes are highly ambitious and subject to change.”
The researchers have purposefully remained tight-lipped about their predicted timelines
for a public rollout of the vaccine.
Prof John Bell, a researcher working on the project, explained in a recent (30th April)
statement to CNN that the first results should be available in mid- June. Several hundred
people have been vaccinated to date. "If we can see evidence of a strong immune
response by the middle or the end of May, then I think the game is on,” he said, adding
that the next step would then be “the massive issue of how you manufacture at scale many
billions of doses.” To this end the Oxford University team is partnering with the
pharmaceutical company AstraZeneca, with the aim of manufacturing the vaccine on a
large scale.
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The Oxford trial is the first in the UK, but several other human vaccine trials are now
underway in the US.
Moderna and Inovio have started their trials, and several other research groups have
expressed interest in rolling out trials in the coming weeks.
Predictive Oncology has launched an AI Platform for the discovery and development of
vaccines against coronavirus. The company has signed an agreement with
InventaBioTech to acquire Soluble Therapeutics, which provides it with access to the
HSCTM Technology.
Predictive will use the HSCTM Technology along with its predictive modeling platform to
deploy an AI discovery platform that can screen the ideal combination of additives and
excipients for protein formulations.
22. Sanofi
In pre-clinical studies, the SARS vaccine candidate was immunogenic and afforded partial
protection as assessed in animal challenge models, Phase 1 human studies are between
March 2021 and August 2021.
Sanofi expects to produce 600 million doses next year if its clinical trials with
GlaxoSmithKline (GSK) goes as planned.
Tonix said February 26 it has partnered with Southern Research to develop TNX-1800 as
a vaccine treatment for COVID-19. TNX-1800 is under development as a potential
smallpox preventing vaccine for the U.S. strategic national stockpile and as a monkeypox
preventing vaccine.
Tonix Pharmaceuticals Holding Corp and the University of Alberta, a leading Canadian
research university, have announced a new research collaboration and exclusive licensing
agreement for three new vaccines for the prevention of COVID-19, the novel coronavirus
disease identified in 2019 which is caused by SARS-CoV-2 virus
TNX-801 and TNX-1800 are in the pre-IND stage and have not been approved for any
indication.
25. Vaxart
Vaxart said January 31 that it plans to generate vaccine candidates based on the
published genome of the 2019 COVID-19 (SARS-nCoV-2) and evaluate them in preclinical
models based on their ability to generate both mucosal and systemic immune responses.
It has five vaccine candidates for preclinical testing
The company plans to start a Phase 1 clinical trial in the U.S. in the second half of 2020,
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THERAPEUTIC DRUGS
Antiviral therapy
Fabiravir and ribavirin
Lopinavir/ritonavir
Remdesivir
Arbidol
Chloroquine and hydroxychloroquine
Antibacterial therapy
Adjunctive interventions
Corticosteroids
Thymosin alpha-1
Cyclosporine A
Interferons
Gammaglobulin
Tocilizumab
Convalescent plasma
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24
ASHP Pharmacists Advancing Healthcare - Assessment of Evidence for COVID-19-Related Treatments: Updated 4/24/2020
VACCINATIONS & THERAPEUTIC DRUGS
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1. AbbVie
HIV-1 protease inhibitor indicated in combination with other antiretroviral agents for the
treatment of HIV-1 infection in adults and children 14 days old and older.
This is one of the four drugs/drug combinations which is under review by the World Health
Organisation (WHO). It was shown to be effective against severe acute respiratory
syndrome (SARS) in vitro, and in some clinical trials. Like umifenovir, lopinavir/ritonavir is
included in the latest Chinese guidelines using a 200 mg/50 mg capsule at a dose of 2
capsules twice a day for up to 10 days. The medication is being studied alone and in
combination with other agents including ribavirin and interferon.
In a completed trial, on 199 patients with severe SARS-CoV-2 infection in Wuhan, China,
showed no benefit beyond standard care. Whether earlier intervention is more beneficial
should be subject of further studies [Cao B, et al NEJM March 18, doi: 10.1056/NEJMoa2001282.]
The combination from published information has been more currently included in French,
Belgium, German, US, Singapore and Japanese Guidelines, and is in phase 3 clinical
trials. Also the combination with the addition of Interferon beta 1a is now part of the
Solidarity clinical trial [ Sallard E, Lescure FX, Yazdanpanah Y, Mentre F, Peiffer-Smadja N. Type 1
interferons as a potential treatment against COVID-19. Antiviral Res. 2020;178:104791.
doi:10.1016/j.antiviral.2020.104791]
According to the Oxford COVID-19 Evidence Service Team, Centre for Evidence-
Based Medicine, Nuffield Department of Primary Care Health Sciences, there is
currently no strong evidence for the efficacy of lopinavir/ritonavir in the treatment of
COVID-19 (April 14th), primary outcomes of time to clinical improvement and negative
pharyngeal SARS-CoV-2 PCR test.
VACCINATIONS & THERAPEUTIC DRUGS
2. AIM ImmunoTech
For the COVID-19 disease early trials started in March in Japan and results have yet to
be announced
3. Airway Therapeutics
4. Algernon Pharmaceuticals
NP-120 (Ifenprodil)
NP-120 can reduce the infiltration of neutrophils and T-cells into the lungs where they can
release glutamate and cytokines respectively. It is already approved to reduce lung
fibrosis in other conditions. There is approval for a phase 2b/3 clinical trial for patients with
advanced COVID-19 lung disease.
5. APEIRON Biologics
APN01
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In addition, the company has secured approvals from regulatory agencies in Austria,
Germany and Denmark to conduct a Phase II clinical trial of APN01 for the treatment of
Covid-19.
6. Ascletis Pharma
Ganovo® danoprevir plus ritonavir; ASC09 and ritonavir; ASC09 and oseltamivir; ritonavir
and oseltamivir;
A clinical study has been published on 11 patients taking danovepir plus ritonavir: The
data from this small-sample clinical study showed that danoprevir boosted by ritonavir is
safe and well tolerated in all patients, of whom 8 patients showed significant clinical
manifestations such as fever, and dry coughing, while 3 patients didn't show significant
clinical manifestation. After 4 to 12-day treatment all eleven patients enrolled, were
discharged well with significantly reuced viral load [Chen H et al. doi:
https://doi.org/10.1101/2020.03.22.20034041].
practice in 1947 to treat malaria. It is also used in the clinical management of autoimmune
diseases including erythematosus lupus and rheumatoid arthritis.
Since adverse effects are quite limited and effectiveness satisfactory, future studies
perhaps should also focus on severe cases to expand the knowledge on its effectiveness.
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9. BenevolentAI
Baricitinib
This already approved drugs for COVID-19 was identified by Benevolent AI using artificial
intelligence. This substance is believed to reduce the ability of the corona virus to enter
the alveolar epithelial cells, probably by blocking the ACE2 pathway.
Baricitinib enters a randomised-controlled trial with the US National Institute of Allergy and
Infectious Diseases (NIAID); predicted to inhibit COVID-19 infection of human lungs and
reduce inflammatory damage.
Baricitinib is an already approved drug developed by Eli Lilly and Incyte for the treatment
of rheumatoid arthritis and is being studied for other indications. The randomised trial
announced by Eli Lilly today with the US National Institute for Allergies and Infectious
Diseases (NIAID) will investigate the efficacy and safety of baricitinib as a potential
treatment for patients with serious COVID-19 infections. The study will begin in the US in
late April with planned expansion to additional sites in Europe and Asia. Results are
expected within the next two months.
10. BeyondSpring
BPI-002
It has the ability to activate CD4+helper T cells and CD8+ cytotoxic T cells, generating an
immune response
11. Biocryst
Galidesivir (BCX4430)
Nucleoside RNA polymerase inhibitor designed to disrupt the viral replication process
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The drug has already shown survival benefits in patients against deadly viruses such as
Ebola, Zika, Marburg, and Yellow fever.
Galidesivir is currently in advanced development stage under the Animal Rule to combat
multiple potential viral threats including coronaviruses, flaviviruses filoviruses,
paramyxoviruses, togaviruses, bunyaviruses, and arenaviruses. For the SARS-CoV-2
virus a clinical trial is initiated in Brazil with 24 patients initially, to be expanded later
according to the initial results. The trial is supported by the NIH (US)
12. BioXyTran
The company will use MDX Life Sciences’ MDX Viewer to assess the safety and efficacy
of the drug.
13. CEL-SCI
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The peptides developed using this technology can help in reducing tissue damage from
inflammation caused due to lung infection, which is a major cause of mortality in elderly
patients.
Tocilizumab (Actemra)
A 94-patient trial assessing Tocilizumab has been registered with Chinese authorities by
The First Affiliated Hospital of University of science and technology of China (Anhui
Provincial Hospital) (ChiCTR2000029765). A phase 2 trial in Italy (this is planned to
include 330 patients hospitalised with first signs of respiratory failure. In addition a
randomised phase 3 clinical trial has been approved by FDA (enrolment is expected to
start in April 2020).
Researchers at Columbia University have been awarded a $2.1m grant by the Jack Ma
Foundation to develop a cure for coronavirus. Four different teams at the university will
adopt various approaches towards the development of a vaccine against coronavirus.
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17. CytoDyn
CytoDyn has initiated a phase 2b/3 randomised clinical trial in the US, targeting 390
COVID-19 patients. It is being proposed as a treatment for mild-to-moderate respiratory
complications that occur in patients with the disease as well as severely and critically ill
patients.
The randomized, double-blind, placebo-controlled study will test the efficacy and safety of
leronlimab initially in 75 patients.
The hyperimmunes are polyclonal antibodies derived from plasma, which are capable of
generating an immune response and protecting against infection. Product candidate
derived from human plasma is named COVID-HIG, while COVID-EIG is derived from
equine plasma. Both will be explored for the treatment of patients with a severe case of
infection.
Enanta Pharmaceuticals has announced its plans to develop antiviral drug candidates to
treat COVID-19 patients. The company is testing compounds from its existing antiviral
compound library for potential efficacy in treating COVID-19. It has also launched a drug
discovery programme to develop direct-acting drug candidates to treat COVID-19.
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Broad spectrum anti-viral agent that is designed to selectively and potently inhibit the RNA-
dependent RNA polymerase (RdRp) of RNA viruses. Japan has approved Avigan for novel
or re-emergent influenza and was previously used to treat Ebola patients in Guinea.
Apart from trials in Japan, This promising anti-viral is currently being tried in several
countries, in phase 3 trials.
Cyprus is also participating in this trial with 20 patients. Study shown that use of 1600mg
twice the first day and 600mg twice daily until the 14th day, gave positive results in
combating COVID-19 as compared to LPV/RTV.
The Russian Direct Investment Fund (RDIF) with a local drug maker will start the
production of a new drug designed analogue of the favipiravir drug initially developed by
Fujifilm Holdings approved for the treatment of influenza in Japan in 2015 and showed
effectiveness in patients with coronavirus and Shenzhen.
The trade name is AVIGAN and the plan is to produce 600.000 packages this year.
Several phase 3 clinical trials are ongoing at present. The only known results are from the
university of Chicago, where 125 cases have been recruited for phase 3 trial and have
responded well to IV remdesivir [https://www.jagranjosh.com/general-knowledge/what-is-
remdesivir-and-can-it-be-useful-in-treating-covid19-1586947150-1]. It has been shown
that the drug can reduce recovery time by about 30%. Based on these initial favourable
results the WHO has included this anti-viral agents in its Innovator trial and the US FDA
has approved it for emergency use in this pandemic, based on a study involving 1063
patients. There have been some negative results from a trial in China but this was
regraded a small case experience.
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1. The National Institute of Allergy and Infectious Diseases trial has enrolled patients in a
randomized, double-blind, placebo-controlled Phase 3 trial evaluating 1,063 hospitalized
patients with COVID-19 at 68 sites worldwide, including at three sites in Singapore and
South Korea, according to the NIAID. However, the majority of the study locations are in
the U.S. The study began Feb. 21 and is expected to conclude April 1, 2023.
Results: It was reported on April 16 that University of Chicago Medicine researchers saw
“rapid recoveries” in 125 COVID-19 patients remdesivir, though that data isn’t part of the
full clinical trial data set.
What’s next: Gilead plans to donate 1.5 million vials, about 140,000 10-day courses of
treatment, of the drug through June. It also said on May 5, that it plans to contract with
pharmaceutical manufacturers abroad to ensure access to remdesivir outside of the U.S.
At this time, evaluation of an oral version of remdesivir has not been proposed and it is
unknown if this antiviral would be useful for patients whose symptoms are not severe
enough to warrant hospitalization.
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VACCINATIONS & THERAPEUTIC DRUGS
Chinese clinical trials assessing the combination treatment have been registered by
Wuhan Jinyintan Hospital (Wuhan Infectious Diseases Hospital) (ChiCTR2000029806)
and Southeast University (NCT04268537). At present (May 2020) no updated data have
been made available
Brilacidin -Defensin mimetic in Phase II development in oral muscositis in Head and Neck
Cancer patients
Janssen has provided DVR-based medicines to support three clinical studies in China.
Unpublished results from one clinical study show that five days of darunavir and cobicistat
was not effective in treating COVID-19. As further preclinical and / or clinical data become
available, thjis information will be updated
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On April 24th, Mateon published a report in the biomedical journal Annals of Pulmonary
and Critical Care Medicine regarding the medical-scientific rationale for its planned
randomized, placebo-controlled, Phase 2 Study of OT-101 (TGF-β inhibitor) in COVID-19
patients with hypoxemic respiratory failure. [Uckun FM, Trieu V. Medical-Scientific
Rationale for a Randomized, Placebo-Controlled, Phase 2 Study of Trabedersen/OT-101
in COVID-19 Patients with Hypoxemic Respiratory Failure. Annals of Pulmonary and
Critical Care Medicine 2020; 3(1); 01-09, and Hwang L, Cynthia L, Vuong N Trieu. COVID-
19 Epidemic: China and ex-China. Open Acc Biostat Bioinform. 3(1). OABB.000552. 2020.
DOI: 10.31031/OABB.2020.03.000552.]
26. NanoViricides
Broad-spectrum virus-binding ligand: “It is like a ‘Venus-Fly-Trap’ for the virus,” says Anil
R. Diwan, PhD, President and Executive Chairman.
The Company has worked on developing an animal model to test anti-coronavirus
effectiveness in vivo using a model coronavirus that binds to the same ACE2 ("angiotensin
convertase enzyme 2") receptor as SARS-CoV-2, namely human coronavirus NL-63
(hCoV-NL63). The Company anticipates using this animal model to obtain indications of
effectiveness of the nanoviricide test drug candidates against the model coronavirus in
vivo.
27. Novartis
Jakavi® (ruxolitinib)
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VACCINATIONS & THERAPEUTIC DRUGS
A global phase III clinical trial evaluating ruxolitinib (Jakafi) in combination with standard
of care for the treatment of cytokine storm associated with coronavirus disease 2019
(COVID-19) in patients 12 years and older has been initiated, was announced by Incyte
on April 21st. This is the first randomized, placebo-controlled phase III study to evaluate
the efficacy and safety of this indication.
28. OyaGen
OYA1 has been found effective in inhibiting SARS-COV-2 from replicating in cell culture.
OYA1 was approved earlier as an investigative drug for cancer but abandoned due to lack
of efficacy.
Now, OyaGen has announced positive findings from collaborative research of a drug
candidate, OYA1, for Covid-19 treatment. The research was conducted in partnership with
the National Institute of Allergy and Infectious Diseases’ Integrated Research Facility.
29. Pfizer
Pfizer announced that it has identified certain under development antiviral compounds that
may be effective in treating coronavirus. The company is planning to partner with a third
party to screen and identify potential compounds by the end of March and begin testing in
April.
30. Pharmstandard
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VACCINATIONS & THERAPEUTIC DRUGS
conducting the monotherapy trial (NCT04260594), while various Chinese hospitals are
investigating the combination therapies
(NCT04252885, NCT04273763, NCT04261907, NCT04286503).
Umifenovir (Arbidol) monotherapy offers little benefit, according to a study published
online April 17 in Med.
Kevzara® (sarilumab)
It will test 400 patents in about 16 US sites. The aim is to evaluate if the drug lessens
patient fevers and their need for supplemental oxygen. The Phase 3 trial will evaluate if
Kevzara prevents deaths and reduces need for mechanical ventilation, supplemental
oxygen, or hospitalization.
The next phase of the study will also only include a higher dose of the drug (400 milligrams)
and the placebo, and not the lower dose of 200 milligrams used in the mid-stage trial.
33. Roche
Actemra
In a small 21-person trial in China it was found that some patients on Actemra, reported
reductions in fever, and 7% of them had a reduced need for supplemental oxygen within
days of starting treatment.
Actemra is also being further evaluated in a clinical trial in China, which is expected to
enroll 188 coronavirus patients. The clinical trial is expected to be conducted until May 10.
In addition, Roche has initiated a Phase 3 clinical trial evaluating Actemra as a treatment
for patients with COVID-19 who have been hospitalized with severe pneumonia. Around
330 patients are being enrolled in 55 sites in the U.S. and elsewhere in the world. The
company plans to examine patient mortality and need for mechanical ventilation or an
intensive care unit stay among other primary and secondary endpoints. Results are
expected in early summer.
Southwest Research Institute is using its virtual screening called Rhodium to identify
potential drug candidates for treating coronavirus from more than two million drug
compounds. The most promising compounds will be identified for further development.
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These antibodies have the potential to generate an immune response when injected into
a new patient, but are still in a preclinical phase.
The Company has submitted (APRIL 2020) a provisional patent application for the
delivery technology. Following this it will be introduced to clinical trials.
Vir has also partnered with Alnylam Pharmaceuticals to identify siRNA candidates
targeting SARS-CoV-2. The companies said they aim to file for an investigational new
drug application by the end of 2020.
Starting Feb. 25, the company is collaborating with Shanghai-based WuXi Biologics to
test monoclonal antibodies as a treatment for COVID-19 in China and elsewhere.
It has formed another partnership with Biogen for cell line and process development and
manufacturing of the antibodies.
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VACCINATIONS & THERAPEUTIC DRUGS
Monoclonal antibody drugs may also fall into the category of passive immunity since they
target specific proteins of the virus. They are being discussed above under drug therapies
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VACCINATIONS & THERAPEUTIC DRUGS
Abbvie’s HIV protease inhibitor, lopinavir is being studied along with ritonavir for the
treatment of MERS and SARS coronaviruses. The repurposed drug is already approved
for the treatment of HIV infection under the trade name Kaletra®.
The combination is listed in the WHO list of essential medicines. Lopinavir is believed to
act on the intracellular processes of coronavirus replication and demonstrated reduced
mortality in the non-human primates (NHP) model of the MERS.
Lopinavir/ritonavir in combination with ribavirin showed reduced fatality rate and milder
disease course during an open clinical trial in patients in the 2003 SARS outbreak.
Cipla is also reportedly planning to repurpose its HIV drug LOPIMUNE, which is a
combination of protease inhibitors Lopinavir and Ritonavir, for the treatment of
coronavirus.
Janssen has no in vitro or clinical data to support the use of darunavir as a treatment for
COVID-19. The drug is in the process of being evaluated in vitro for any potential activity
against the coronavirus.
Further, Janssen has partnered with the Biomedical Advanced Research and
Development Authority (BARDA) to expedite the development of a COVID-19 treatment.
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VACCINATIONS & THERAPEUTIC DRUGS
EMA launched on April 17th an enhanced fast-track monitoring system to help prevent
and mitigate supply issues with crucial medicines used for treating COVID-19 patients.
Under this system, each pharmaceutical company is appointing a single contact point
(industry single point of contact or i-SPOC) who will report to EMA all ongoing or
anticipated shortages of medicines used for treating COVID-19, irrespective of their
authorisation route. This mechanism is similar to the single point of contact (SPOC)
network that EMA and the national competent authorities already use to exchange
information on shortages. Initially, the system will focus on medicines used in intensive
care (such as anaesthetics, antibiotics, resuscitation drugs and muscle relaxants), which
are in greatest demand, before extending to a broader range of medicines.
In addition, EMA offers medicine developers several opportunities for early dialogue and
consultation before submitting a marketing authorisation application. This is intended to
provide regulatory and scientific support to facilitate the preparation of applications and
enable a smooth validation and assessment procedure.
Four drugs or drug combinations already licensed and used for other illnesses will
be tested by WHO and 10 countries have indicated their interest to take part in
the trial:
1. Remdesivir (by Gilead)
2. Lopinavir and Ritonavir (sold as Kaletra or Aluvia by AbbVie)
3. Lopinavir and Ritonavir plus Interferon β; and
4. the antimalarial drug Chloroquine.
FDA allows treatment of life threatening COVID-19 cases using blood from
patients who have recovered. It is a temporary authorization under FDA’s
investigational NEW DRUG APPLICANTS (INDs) exemption.
Convalescent plasma transfusion has been used against H1N1 flu, and SARS
and MERS epidemic with varying results. It is not new and is relatively safe.
May 7th. Convalescent plasma: Trials to treat COVID-19 using the blood plasma
from those who have already recovered from the illness have begun. The first 14
units of convalescent plasma from former coronavirus patients have been
supplied to three NHS trusts, and transfusions have already taken place.
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References
3. BBC News
7. Euronews- Racing for a cure: where are we with COVID-19 vaccines and
treatments?
12. Pan American Journal of Public Health - Clinical trials on drug repositioning for
COVID-19 treatment
13. Pharmacy Times - Potential Pipeline Medications May Help Patients With Novel
Coronavirus, 2020-03-11
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14. Springer Open - Therapeutic strategies for critically ill patients with COVID-19
15. STAT news - WHO to launch multinational trial to jumpstart search for
coronavirus drugs
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