Source : 'The Pink Sheet'
Concern is growing that some countries or regions will have first call on limited supplies of potential COVID-19 products at the expense of less well resourced areas of the world. This impression was not dispelled by the announcement that the US government had struck a deal with Gilead Sciences to buy 90% of the available supply of remdesivir over the next three months.
But moves are afoot to try to ensure equitable access to coronavirus treatments, vaccines and tests at global level. The European Commission and Global Citizen, for example, have mobilized €6.15bn (US$6.9bn) in additional funding to “develop and ensure” equitable access and support economic recovery “in the world’s most fragile regions and communities.”
The total, which was pledged during a 27 June summit, includes €4.9bn from the European Investment Bank (EIB) in partnership with the commission, and €485m from EU member states, bringing the total pledges under the Coronavirus Global Response effort to €15.9bn.
40 governments took part in the summit and “committed to ensuring universal access to coronavirus medicines,” the commission and EIB said. “As a landmark of global solidarity, the summit resulted in commitments for the production capacity of over 250 million vaccine doses for middle and lower income countries.”
According to commission president Ursula von der Leyen, the world "will only be freed from this pandemic when vaccines, tests and treatments are available and affordable to everyone who needs them. Today’s pledges and Europe’s contribution bring us closer to this global goal.”
The EIB said it was building a pipeline of investment projects to develop and scale up production of coronavirus vaccines, tests and treatments, in partnership with the commission, the World Health Organization and the Coalition for Epidemic Preparedness Innovations (CEPI).
The WHO and CEPI are also involved in the Access to COVID-19 Tools (ACT) Accelerator, a landmark international initiative that was launched in April with the aim of ensuring that everyone has access to “all the tools to prevent, detect, treat and defeat COVID-19.” ("WHO Launches Global Push For Tools To Tackle COVID19" "Pink Sheet" )
On 26 June the ACT Accelerator partners issued an “Investment Case” document calling for donor funding commitments. It says that a total of US$31.3bn is needed for three of the funding streams: US$18.1bn to pay for COVID-19 vaccines by the end of 2021, US$7.2bn for therapeutics in low and middle-income countries by mid-2021, and US$6bn for coronavirus tests in LMICs, also by mid-2021.
The funding requirements for the fourth stream – the “Health Systems Connector, which aims to ensure the technologies reach those who need them – are currently being worked out.
“We must continue to build on the momentum and promise of the ACT-Accelerator by rapidly addressing the most immediate financial needs of each pillar, to enable them to deliver their full impact,” the document says, noting that financial donors “have full oversight on the allocation of their pledges.”
“This Investment Case will be updated as needed in the early fall of 2020, as the first ACT-Accelerator milestones for product development are achieved and more epidemiological data becomes available,” it adds.
On the regulatory front, the European Medicines Agency said on 1 July that it had endorsed a joint statement on the prioritization of COVID-19 clinical trials published by the International Coalition of Medicines Regulatory Authorities (ICMRA).
The statement was developed following a series of meetings among ICMRA members on priority criteria for planned trials to allow the rapid assessment and approval of candidate products. “Medicines regulators from around the world have jointly developed this statement to step up global collaboration to facilitate and expedite the development and evaluation of therapeutics, diagnostics and vaccines against COVID-19,” the EMA noted.
The statement describes the key characteristics of trials that are most likely to generate the conclusive evidence needed to allow accelerated approval, and sets out the actions stakeholders should take to collect, analyze and report clinical data. Priority trials are considered to be confirmatory trials that address unmet medical needs, have a methodologically robust design, and are sufficiently powered to show reliable results. They should be testing products that already have human data or are in Phase II studies, and that are intended to treat the most severe complications of COVID-19, such as acute respiratory lung injury, cytokine storm, multisystem inflammatory syndrome in children, and thrombotic complications.
“Medicines regulators also encourage investigators to make the results fully and quickly accessible, both to participants in the clinical trials and the public so that the global research community can benefit from that information,” the EMA added.
The EMA has also signed an agreement with South Korea’s Ministry of Food and Drug Safety on the sharing of confidential information on medicines for the treatment, diagnosis and prevention of coronavirus infection. The agreement is “an ad-hoc arrangement that focuses exclusively on COVID-19” and complements the EMA’s existing confidentiality arrangements with other countries and organizations, the EMA noted.
Separately, the agency said it had decided to continue holding its committee and working party meetings virtually until the end of September. Other stakeholder events planned before that time will either be postponed or held virtually, it added.
Amid discussions on the availability and affordability of COVID-19 products, studies of potential new products and vaccines are continuing.
On 1 July, Pfizer and BioNTech announced positive early data from their Phase I/III study of the most advanced of a number of investigational mRNA-based vaccine candidates, BNT162b1, which is being tested in 45 healthy adults aged 18-55. The BNT162 program, dubbed Project Lightspeed, is evaluating at least four experimental vaccines against the SARS-CoV-2 virus.
Ugur Sahin, CEO and co-founder of BioNTech, said: “These preliminary data are encouraging, showing that BNT162b1, which exploits RBD SARS-CoV-2 as a target antigen, is able to produce neutralizing antibody responses in humans at or above the levels observed in convalescent sera – and that it does so at relatively low dose levels.” Local reactions and systemic events after immunization with 10µg and 30µg of BNT162b1 were dose-dependent, generally mild to moderate, and transient, and no serious adverse events were reported, the companies said.
Further data from the trial of four vaccine candidates “will enable selection of a lead candidate and dose level for a large, global Phase IIb/III safety and efficacy study that may begin as early as July 2020,” they declared. If the safety and efficacy study is successful, and the vaccine receives regulatory approval, the companies expect to manufacture up to 100 million doses by the end of 2020 and potentially more than 1.2 billion doses by the end of 2021.
“In that event, BioNTech and Pfizer would work jointly to distribute the potential COVID-19 vaccine worldwide (excluding China, where BioNTech has a collaboration with Fosun Pharma for BNT162 for both clinical development and commercialization).”
Clinical trials of the vaccine candidate developed by Oxford University’s Jenner Institute in the UK are now starting up further afield. Studies have already begun in the UK and Brazil, and now South Africa has joined in too, according to the Gavi vaccines alliance.
The South African trial will enrol 2,000 volunteers aged 18-65 and will include some HIV-positive patients, Gavi said. The new study comes after the African Union endorsed the need for Africa to develop a framework to actively engage in the development and access to COVID-19 vaccines, the alliance noted. The first African case of COVID-19 was reported in mid-February, and as of 24 June the continent had 236,090 cases and 5,257 deaths, according to the WHO. The Brazilian study is testing the vaccine in 2,000 health workers in Sao Paulo and 1,000 in Rio de Janeiro.
On 1 July the Dutch translational vaccinology R&D organization, Intravacc, announced it had teamed up with compatriot company CimCure to license the latter’s iBoost vaccine technology, which is currently used to elicit antibody responses against tumor vasculature, “a strategy that conquers the problem of drug resistance,” Intravacc said. The two organizations are also using the technology to develop a COVID-19 vaccine, with CimCure and the Amsterdam University Medical Center having received a €1.3m grant from Health Holland, an investment organization of the Ministry of Economic Affairs. “In the collaboration, CimCure will focus on the design and preclinical validation of three different types of COVID-19 vaccine concepts, while Intravacc will be responsible for the vaccine process development, the pilot production of the candidate vaccine under GMP [good manufacturing practice] conditions and for a phase I clinical trial,” Intravacc said.
Some Nordic life science companies are carrying out research on potential coronavirus treatments. UNION Therapeutics of Denmark has just received approval from the Danish Medicines Agency to begin a clinical trial of UNI9011, an optimized salt form of niclosamide as a candidate COVID-19 treatment that has been identified as a potent inhibitor of SARS-CoV-2 by the company’s partner, Institut Pasteur Korea. “Niclosamide has the potential to become a truly differentiated treatment of COVID-19, effectively blocking replication of SARS-CoV-2 by targeting host cells to disrupt the viral life cycle,” UNION said. The company has been working with niclosamide, an oral anthelmintic, for more than six years and is currently conducting a Phase IIb study of the substance in patients with atopic dermatitis.
In Finland, meanwhile, Faron Pharmaceuticals’ investigational drug Traumakine is being tested in the WHO’s Solidarity trial investigating potential COVID-19 treatments. Traumakine (recombinant human interferon beta-1a) has orphan drug status and is being developed to treat acute respiratory distress syndrome and other conditions; in the Solidarity trial it is being tested together with the HIV combination, lopinavir plus ritonavir.
Another Finnish firm, the Turku-based contract manufacturer Biovian, has signed an agreement with a European drug development company for the initial production of a COVID-19 vaccine. The contract covers the early-stage development and purification of the candidate; Biovian said that because of non-disclosure agreements, details of the project were being kept confidential.
Other potential COVID-19 products are having mixed fortunes. Hydroxychloroquine, whose reputation as a candidate treatment has plummeted as a result of negative results, safety issues and the suspension of some clinical trials, is seeing something of a resurgence, at least in the prevention sphere.
The UK regulatory agency, the MHRA, has approved the re-start of the COPCOV trial, in which the University of Oxford is exploring the drug’s potential in preventing COVID-19 infection. The request to recommence recruitment was made by the university.
“The submitted justifications and supporting information were reviewed by the MHRA, with independent advice obtained from the Commission on Human Medicines,” said Siu Ping Lam, the agency’s director of licensing. “On 26 June it was agreed that sufficient measures had been taken to support the safe recruitment of further participants,” Lam said. “Participant safety is our priority, so we will continue to monitor the trial to ensure ongoing appropriate measures are in place to maintain continued high levels of safety.”
But there was disappointing news for lopinavir/ritonavir when it was announced that a UK study had found “no clear benefit” in treating COVID-19 patients with the combination. Researchers at the Drug Safety Research Unit in Southampton screened more than 460 research papers about the combination before analyzing the risks and benefits of using them in severe COVID-19 cases.
“The benefit risk study, published in the journal Drug Safety, shows lopinavir-ritonavir provides no significant difference in the time to clinical improvement in comparison to standard care,” the DSRU said.
Researchers noted fewer cases of acute respiratory distress syndrome with lopinavir-ritonavir compared with standard care (13% vs 27%) in one study. There also appeared to be fewer serious adverse events with lopinavir-ritonavir: 20% versus 32% from standard care.
“However, the limited amount of data available led researchers to conclude the benefit-risk profile for lopinavir-ritonavir for severe COVID-19 could not be considered ‘positive’ until more efficacy and effectiveness data became available,” the DSRU said.
It added that the findings echoed the announcement from the Oxford University Recovery trial, which is looking at various treatments for COVID-19 including lopinavir/ritonavir, low-dose dexamethasone, and hydroxychloroquine.
Professor Saad Shakir, Director of the DSRU, said: “Currently, our research shows no clear benefit in treating severe COVID-19 patients with lopinavir-ritonavir but we will monitor new findings and update our benefit-risk evaluation as soon as these become available.”
To help those wanting more detail on the epidemiology of COVID-19 in different countries, the European Centre for Disease Prevention and Control (ECDC) has produced a new “COVID-19 Country Overview” page that includes graphs of 14-day case and death notification rates, hospital and intensive care unit occupancy rates, and several other indicators. The report complements the detailed presentation of epidemiological data in the ECDC’s weekly surveillance report and the interactive ECDC COVID-19 dashboard. For details visit https://covid19-country-overviews.ecdc.europa.eu/
By Ian Schofield