Coronavirus Update: Old Drugs, New Trials, And Brexit
Executive Summary
In addition to our daily in-depth coverage of key events relating to the COVID-19 pandemic, we’re bringing you a periodic round-up of other developments. This edition covers events at the national, EU and global level.
This latest edition of the Pink Sheet’s coronavirus updates covers events including new studies of a gout drug to help stem the inflammatory cascade in coronavirus patients, an EU “solidarity pact” to help speed up R&D, and an expedited clinical trial review process in Ireland.
Old Drugs In New Trials
Many existing medicines are being tested in an effort to find treatments for patients who are seriously ill with COVID-19 infection. Among the more recent candidates is colchicine, an old anti-inflammatory drug that is widely used to treat gout and is now in clinical trials in a number of locations.
Canada
One of these is the Canadian COLCORONA trial led by the Montreal Heart Institute. This is a 6,000-patient, randomized, double-blind, placebo-controlled, multi-center study that aims to determine whether short-term treatment with colchicine can reduce excessive inflammation, help the body’s immune system fight the coronavirus, and reduce the complications of pneumonia, organ failure and death.
Greece
GRECCO-19 is a Phase II Greek study looking at whether low-dose colchicine (0.5mg twice daily) can limit the development of myocardial necrosis and pneumonia in 180 COVID-19 patients. The study, which is sponsored by the National and Kapodistrian University of Athens, is expected to run until September.
Italy
In Italy, the drugs regulator AIFA has announced the start of recruitment for COLVID-19, a multicenter, randomized Phase II trial of colchicine sponsored by the department of medicine at Perugia hospital center. The study aims to recruit more than 300 patients with COVID-19 pneumonia who need assistance in breathing.
AIFA has also given details of some compassionate-use coronavirus projects it is pursuing. They include two managed access programs, one for Novartis’s Ilaris (canakinumab) for the treatment of cytokine release syndrome (CRS) in patients with COVID-19-induced pneumonia, and Jakavi (ruxolitinib) in patients with severe or very severe lung disease.
Scottish Research Venture
New avenues of research into potential treatments may also be opened up by a new Scottish venture launched by the Centre for Inflammation Research at the University of Edinburgh. The aptly-named STOPCOVID project will focus on the inflammatory pathways that can lead to lung injury in coronavirus patients, and will test various drugs to see whether they can block this inflammation in the early stages of the disease.
STOPCOVID, which is based at the Edinburgh Bioquarter, has secured £2m in funding from the medical research charity LifeArc, and says it aims to raise a total of £15m from the private sector. The research team said it was working with pharma firms across the world and had “already identified key drugs and mechanisms that are currently in development or are being used for other diseases.” Any drugs that provide positive early results will be fast tracked into national and international clinical trials, it added.
French Side-Effects Study
Other medicines are already being used or tested in COVID-19 patients, notably the malaria/arthritis drug hydroxychloroquine and the antiviral combination product lopinavir/ritonavir (AbbVie Inc.’s Kaletra). As with all medicines, though, they have numerous unwanted side-effects, and so the French regulatory agency ANSM and the national pharmacovigilance network have been looking into the potential safety issues.
They have been monitoring the use of these two products outside clinical trials, and found that their safety risks, particularly cardiovascular events, may be higher in coronavirus patients. The regional pharmacovigilance centre (CRPV) in Dijon found about 100 cases of adverse events linked to their use in coronavirus patients, of which 82 were serious (including four deaths), spread about equally between the two products. ANSM then asked the CRPV in Nice to conduct a further survey of 53 cardiovascular events, 43 of them linked to hydroxychloroquine alone or in combination (mostly with azithromycin), including cases of sudden death, syncope, and QT interval prolongation.
“This first assessment shows that the risks, particularly cardiovascular, associated with these treatments are indeed present and possibly increased in patients with COVID-19," the agency declared. It said the drugs should be used only in hospitalized patients under “strict medical surveillance”.
Belgium Backtracks On Export Ban
The sharp rise in demand for products like hydroxychloroquine, Kaletra and other medicines used to treat coronavirus patients is leading to shortages in many markets, and countries have taken steps to restrict their use to the hospital setting or to preserve stocks by limiting exports.
Belgium, for example, implemented a temporary ban on the export of certain medicines outside the European Economic Area at the beginning of the month. However, it has now backtracked somewhat and on 8 April introduced a system of export controls instead. “Coincidentally or not, the same day the European Commission also issued guidelines to the member states on the rational supply of medicines,” noted Covington & Burling, which had questioned whether aspects of the ban contravened EU rules. (Also see "Belgium Imposes Selective Export Ban As COVID-19 Threatens Stocks" - Pink Sheet, 6 Apr, 2020.)
The law firm said that the latest decision by the Belgian federal medicines agency had “essentially reversed the total export ban.” The decision says that exports outside the EEA can be refused if there is an “acute or imminent shortage of the relevant medicines or raw materials, insofar the available volumes are insufficient to fulfill the needs of patients in Belgium during the upcoming four weeks,” Covington & Burling added.
“The availability of an alternative, therapeutic equivalent alternative is taken into account, as well as the needs for the treatment of COVID-19 patients, on the basis of current epidemiological models and taking into account standard dosages,” the law firm said. “This new approach is likely compliant with EU law. Exports are in principle allowed, and the authority gives clear public health criteria that could be a ground for refusal.” It added that Article 3(2) of the decision had been redrafted to reflect that exports to the EEA are in principle permitted as long as there is prior notification and the product is destined for supply or administration in the destination EEA member state.
EU Solidarity Pact
The availability of medicines also figures in recent initiatives at EU level, where the European People’s Party, the largest grouping in the European Parliament, has adopted a “Solidarity Pact” that aims to protect people and businesses from COVID-19 and to provide a “long-term plan to strengthen Europe’s response to such crises in the future.” The pact includes proposals to “reject all national bans on the export of medicine and medical equipment to other EU member states” and calls on the European Commission to “explore all ways to prevent national measures from altering the correct functioning of the Single Market.”
The EPP also wants to “intensify EU medical research to enable speedy results from research on a vaccine as well as treatment against the coronavirus” and says the European Medicines Agency should “fast-track procedures for testing and approving COVID-19-related medicines or vaccines.”
The EPP’s proposals include coordinating vaccine production to ensure that, “once available, hundreds of millions of vaccines can be produced in a short period of time and made available at a fair price, taking into account the public investment in this research.” The vaccines proposal was welcomed by Ancel·la Santos of the NGO Health Action International Europe, although she tweeted: “I miss a comment about the need for good evidence on safety & efficacy. Important message.”
The EU has gone further and submitted a draft resolution for the next World Health Assembly, which is expected to meet in May in virtual form with COVID-19 as the focus, according to the activist organization Knowledge Ecology International. The six-page draft says that a plan should be drafted, in consultation with World Health Organization member countries, to achieve “equitable access to quality, safe, and efficacious COVID-19 vaccines and other health technologies necessary for COVID-19 response.”
The idea is that the plan should have input from relevant international organizations including WIPO, GAVI, UNITAID, the Medicines Patent Pool, CEPI, the Global Fund to fight Aids, TB and Malaria, and UNICEF, says KEI. Among other things the resolution states that the private and public sectors should work together on medicines, vaccines and diagnostics including “voluntarily pooling their intellectual property for all COVID-19-related medical interventions.”
Expedited Trial Approval
Many countries have already chosen to implement rapid evaluations of applications for coronavirus-related research. Ireland is among the latest to take this route, with the regulatory agency, the HPRA, giving priority review to all applications for relevant drug or medical device clinical trials. In addition, the health ministry has set up a temporary COVID-19 national research ethics committee (NREC-COV19) that will evaluate applications for ethics review concurrently with the regulatory review, the aim being to produce an expedited national decision. Research covered by the NREC-COV19 review process includes basic, translational and clinical research, diagnostics and treatment, population health research and applied health policy research. Responsibility for ethics review will revert to the normal distributed ethics committee system “once the peak volume of applications has been processed and projects are underway,” the Irish Health Protection Board noted.
Technology News
On the technology front, Excelra, a global data and analytics company, has announced the release of the COVID-19 Drug Repurposing Database. The open-access database is a compilation of previously approved small molecules and biologics with known preclinical, pharmacokinetic, pharmacodynamic and toxicity profiles that can rapidly enter Phase II or III clinical trials for COVID-19 on a fast-track basis, the company says. The database also includes information on promising drug candidates that are in various clinical, preclinical and experimental stages of drug discovery and development for COVID-19.
Meanwhile Atos, a digital transformation company, said its BullSequana X1000 supercomputer installed at the UK Hartree Centre, part of the Science and Technology Facilities Council (STFC), is providing supercomputing power to help in global computational drug discovery efforts to help combat COVID-19. The Hartree Centre team is working closely with Washington University School of Medicine, which leads the Folding@home project under which a global community of contributors can lend unused background capacity on their personal computers to conduct simulations of target drug interactions.
More Funding Please
Many of those working on coronavirus research need funding, and the Coalition for Epidemic Preparedness Innovations (CEPI), a partnership between public, private, philanthropic and civic organizations, is no exception. It has joined the new COVID-Zero initiative, which aims to help raise at least $8bn by the end of April to cover a global funding shortfall for vaccines, treatments and testing for coronavirus. “The Global Preparedness Monitoring Board, an independent body convened by the World Health Organisation and the World Bank, has identified an urgent $8bn shortfall in scientific funding, of which $2bn is needed by CEPI to support the development of safe and effective vaccines,” CEPI says. “COVID-Zero is calling on business to form a coalition that can help bridge this funding shortfall and get our lives, businesses and economies back on track. The initiative is called COVID-Zero because by securing this funding, it aims to achieve zero deaths, zero new cases and zero lockdowns as soon as possible.”
IMF: “Extend The Brexit Transition Period”
The coronavirus has of course wrought havoc with talks on the post-Brexit relationship between the UK and the EU. Amid fears that the parties will not manage to reach a deal by 31 December when the transition period expires, the managing director of the International Monetary Fund, Kristalina Georgieva, has called on the UK and EU to agree an extension to the transition period. "It is tough as it is. Let's not make it any tougher," Georgieva, a former European Commissioner for humanitarian aid, told BBC radio. "My advice would be to seek ways in which this element of uncertainty is reduced in the interests of everybody, of the UK, of the EU, the whole world."
However, any extension would have to be agreed by 30 June, and the UK government is having none of it. “We will not ask to extend the transition period and if the EU asks we will say no,” said prime minister Boris Johnson’s spokesman. “Extending the transition would simply prolong the negotiations, prolong business uncertainty and delay the moment of control of our borders.” The spokesman added that this “would also keep us bound by EU legislation at the point where we need legislative and economic flexibility to manage the UK response to the coronavirus pandemic.”