LIVE BLOG: R&D response to COVID-19 pandemic

17 Jun 2021 | Live Blog
Covid 19 blog

The coronavirus pandemic is disrupting universities and research institutes across the world. But the same institutions are also working very hard to find out how the disease can be stopped and its effects mitigated.

Follow this live blog for the latest updates on how the crisis is impacting research and innovation, and what governments, funders, companies, universities, associations and scientists are doing to stop or cope with the pandemic.

You can read the full archive of this blog here.

Partners Sanofi and GlaxoSmithKline say they are on track to get approval of their COVID-19 vaccine before the end of the year, after reporting positive results from a phase II trial.

The vaccine was initially expected to be approved in the first half of 2021, but the companies had to go back to the drawing board after an earlier phase II that reported last December found there was an insufficient immune response in people aged 50 and over.

In the latest trial, involving 722 volunteers, the product achieved strong rates of neutralising antibody responses after two doses, in line with those measured in people who have recovered from COVID-19. A phase III study is expected to start in the coming weeks.

After a single injection, high neutralising antibody levels were generated in those volunteers who had recovered from a natural SARS-CoV-2 infection, suggesting there is potential to develop the vaccine for use as an immune booster.

"Our phase II data confirm the potential of this vaccine to play a role in addressing this ongoing global public health crisis, as we know multiple vaccines will be needed, especially as variants continue to emerge, and the need for effective and booster vaccines, which can be stored at normal temperatures, increases,” said Thomas Triomphe, head of Sanofi Pasteur. “We are set to progress to a global phase III efficacy study.”

The phase III trial is expected to enrol more than 35,000 participants in a number of countries and will assess the efficacy of two formulations, against the original virus that emerged in China and the B.1.351 South African variant that has shown some resistance to first generation COVID-19 vaccines.

In parallel, the companies intend to conduct booster studies with various variant formulations in order to assess the ability of a lower dose of the vaccine to generate a strong booster response regardless of the initial vaccine received.

The clinical studies to date have been financed by the US Biomedical Advanced Research and Development Authority.

The EU Health Security Committee (HSC) has agreed to update the common list of COVID-19 rapid antigen tests, easing the way for the EU’s single digital vaccine certificate to allow foreign travel.

Following the update, 83 tests are now included in the common list, of which the results of 35 tests are mutually recognised by all member states.

Commissioner for health, Stella Kyriakides, said, “Rapid antigen tests play a crucial role to slow down the spread of COVID-19. Having a wider list of recognised rapid antigen tests will make it easier for citizens to benefit from digital green certificates and to facilitate safe free movement inside the EU in the coming months.”

In addition, the Commission and the Joint Research Centre have agreed a new procedure for updating the list of common and mutually recognised tests in the future. In future, there will be a common procedure for carrying out independent validation studies to assess the clinical performance of rapid tests.

The European Commission launched a strategy to support development of, and access to, COVID-19 therapies, including for the treatment of people who have recovered from the acute phase of infection but are now suffering from long COVID.

The strategy, intended to parallel the EU’s efforts in COVID-19 vaccines, is targeting approval of three new treatments for COVID-19 by October 2021, and possibly two more by end of the year. On the back of this, the Commission says it will launch new contracts for the purchase of authorised drugs by the end of the year.

A total of €90 million will be invested in population studies and clinical trials to look for links between risk factors and health outcomes, to further inform public health policy and clinical management, including for long COVID patients.

By July, the Commission will set up a therapies innovation ‘booster’ to support the most promising products through from preclinical research to market authorisation. This will build on current initiatives and investments in drug development, working in a close cooperation with the new European Health Emergency Preparedness and Response Authority, to ensure the coordination of all research projects on COVID-19 therapies.

A further €5 million is to be invested under the EU4Health programme to generate better safety data in clinical trials, to help produce robust results in a timely manner.

EU member states will be eligible for €2 million under EU4Health in 2021, to carry out expedited and coordinated assessments of applications to conduct clinical trials.

In addition, there will be a horizon scanning programme, with €5 million to map therapies and diagnostics and analyse what phase of development they are at, and the production capacities and supply chains. That will inform the establishment of a broader portfolio of ten potential COVID-19 therapies, with the five most promising identified by June 2021.

The Commission is keen not to make the same mistake in therapeutics as it did in vaccines, where despite large advance purchase agreements, there was no support for manufacturing. In this case, it is putting in €40 million to support flexible manufacturing and access to COVID-19 drugs.

The European Medicines Agency said it started a rolling review of a monoclonal antibody developed by GlaxoSmithKline and US biotech Vir Biotechnology for the treatment of COVID-19.

The decision to conduct the accelerated review is based on preliminary results from an ongoing study looking at the ability of the drug, sotrovimab, to prevent hospitalisation or death in patients with COVID-19 being treated in the community.

That would fill a gap in the care pathway, because currently there are no therapies specifically approved for patients at high risk of developing severe COVID-19 who are being treated at home.

Rolling reviews involve looking at data as they become available from ongoing studies, before a formal application is submitted. EMA said while the overall review timeline cannot be forecast yet, the process should be quicker than a regular evaluation.

A separate EMA review of sotrovimab is underway to provide EU-wide recommendations to support national authorities in case they want to use the drug prior to marketing authorisation.

Sotrovimab is designed to attach to the spike protein of SARS-CoV-2, the virus that causes COVID-19, reducing the ability of the virus to enter the body’s cells. Preclinical data suggest it has the potential to both block viral entry into healthy cells and to clear infected cells.

The decision to start the rolling review is based on the interim analysis of efficacy and safety data from the phase III study, which is evaluating sotrovimab as monotherapy for the early treatment of COVID-19 in adults at high risk of hospitalisation.

In March, the independent safety board monitoring the trial recommended it should stop enrolling more patients because there was already evidence of efficacy. Enrolled patients continue to be followed up.

European Commission president Ursula von der Leyen said EU is ready to discuss any proposal that addresses the pandemic crisis in an effective and pragmatic manner, including over-riding patents. “That is why we are ready to discuss how the US proposal for a waiver on intellectual property protection for COVID-19 vaccines could help achieve that objective,” she said in a speech this morning to the State of the Union conference at the European University Institute.

That follows a decision by the US to support the waiver, with US trade commissioner Katherine Tai saying on Wednesday, “The US supports the waiver of IP protections on COVID-19 vaccines to help end the pandemic and we’ll actively participate in [World  Trade Organisation] negotiations to make that happen.”

Von der Leyen’s change in tone is at odds with the European Parliament, which voted against the waiver on 29 April 2021.

European pharma companies joined counterparts elsewhere in the world in condemning the move, with Nathalie Moll, director general of the industry body EFPIA saying, “This short-sighted and ineffectual decision by the Biden administration puts the hard-won progress in fighting this terrible disease in jeopardy. While we wholeheartedly agree with the goal of protecting citizens around the world through vaccines, waiving patents will make winning the fight against the coronavirus even harder.”

Moll said increasing capacity to deliver doses to citizens around the world requires the skills and technical know-how of the vaccine developer to bring on-board partner manufacturing organisations. “You simply cannot achieve this kind of capacity expansion by waiving patents and hoping that hitherto unknown factories around the world will turn their hand to the complex process of vaccine manufacture,” she said.

A waiver also risks diverting raw materials and supplies away from well established supply chains to less efficient manufacturing sites and opens the door to counterfeit vaccines entering the supply chain around the world, Moll said.

The decision of the US administration to support a patent waiver for COVID-19 vaccines is “disappointing”, according to a statement from pharma companies.

“We are fully aligned with the goal to ensure COVID-19 vaccines are quickly and equitably shared around the world. But, as we have consistently stated, a waiver is the simple - but the wrong answer - to what is a complex problem,” the statement says.

Waiving patents of COVID-19 vaccines will not increase production nor provide practical solutions needed to battle the global health crisis. On the contrary, it is likely to lead to disruption, while distracting from addressing the real challenges in scaling up production and distribution of COVID-19 vaccines globally, the industry says.

Pharma companies hit back after the general council of the World Trade Organisation (WTO) agreed to allow the Council for Trade-Related Aspects of Intellectual Property Rights to continue consideration of the proposal first put forward by India and South Africa for a temporary waiver of certain intellectual property obligations in response to COVID-19.

The waiver had the support of 60 WTO members, but the one that is likely to swing things is the US. “This is a global health crisis, and the extraordinary circumstances of the COVID-19 pandemic call for extraordinary measures. The administration believes strongly in intellectual property protections, but in service of ending this pandemic, supports the waiver of those protections for Covid-19 vaccines,” said US trade representative Katherine Tai in a statement announcing the US had changed its position.

The industry squarely aims at trade barriers it says are holding up supply chains. Another problem that would not be solved by waiving intellectual property rights is shortages of raw materials and other essential items, such as glass vials and filters used in bioprocess of bulk materials.

Demand continues to outstrip supply, but the industry says there should be “willingness” by rich countries to start sharing doses with poor countries.

“We will continue to leave no stone unturned to further scale up manufacturing of COVID-19 vaccines, as no one is safe until everyone is safe,” the statement says.

Companies have voluntarily agreed more than 200 technology transfer agreements to expand delivery of COVID-19 vaccines based on “unprecedented” partnerships, companies say.

Two doses of the Pfizer/BioNTech COVID-19 vaccine provide more than 95% protection against infection, hospitalisation, severe illness, and death, including among the elderly, according to the first national real world assessment of its effectiveness, carried out in Israel,

The study, published in The Lancet, unpicks for the first time the public health benefits of a national vaccination programme. Vaccination was found to be the key driver of a decline in COVID-19 infections in Israel.

The findings are encouraging, but unknowns, notably the duration of immunity to COVID-19 remain. It is also possible that new, vaccine resistant variants could emerge in the future, the authors say.

Lead author, Sharon Alroy-Preis, of the Israel Ministry of Health, said that as the country with the highest proportion of its population vaccinated against COVID-19, Israel provides a unique real-world opportunity to determine the effectiveness of the vaccine. “Until this point, no country in the world had described the national public health impact of a nationwide COVID-19 vaccination campaign. These insights are hugely important because, while there are still some considerable challenges to overcome, they offer real hope that COVID-19 vaccination will eventually enable us to control the pandemic.”

Vaccination with the Pfizer/BioNTech vaccine began amid a surge of infections that led to a national lockdown in Israel on 27th December 2020. Daily infections peaked at 10,213 cases on 20 January 2021, and lockdown was lifted on 7 March 2021.

By 3 April 2021, 72% or 4,714,932 people over 16 years, and 90%, or 1,015,620, of those over 65 years, had received two doses of the Pfizer/BioNTech vaccine.

During the analysis period, there were 232,268 confirmed COVID-19 infections in the country. The most prevalent strain was B.1.1.7, first detected in the UK, which accounted for 94.5% (8,006 of 8,472) of samples tested through Israel’s PCR testing service.

The Pfizer/BioNTech vaccine was highly effective against COVID-19 for all people over the age of 16 years, providing 95.3% protection against infection and 96∙7% protection against death seven days after the second dose. The vaccine is also highly effective in preventing hospitalisation.

Assessing efficacy after one dose of Pfizer/BioNTech vaccine demonstrated the importance of fully vaccinating adults. Protection was considerably lower between seven and 14 days after receiving the first dose, compared to two doses.

The surge in new variants of COVID-19 and an increase in subsequent cases is continuing to have an impact on clinical trials, even though studies are resuming. The total number of disrupted trials has levelled off and the number of clinical trials that have restarted continues to rise, but at a somewhat slower rate than the initial rise.

This implies that sponsors and contract service providers have begun to adjust clinical trial design strategies and are adapting to the new post-COVID-19 environment, according to GlobalData, a data and analytics company.

“Since June 2020, the number of total disrupted trials has been falling slowly; however, this levelled off in October 2020. The majority of current trial disruptions are due to trials impacted by slow enrollment, said Brooke Wilson, associate director, trials intelligence at GlobalData.

Trials that started enrolling before the pandemic, with sites and investigators chosen, but then were suspended due to COVID-19, are “having more success picking up where they left off,” Wilson said.

But overall, the number of trials being impacted by slow enrollment continues to increase.

Methods that could help start or sustain research include virtual visits, phone interviews, self-administration, and remote monitoring. These suggestions could help trials that are being hampered by quarantines, travel limitations, clinical site closures, and interrupted supply chains, especially trials that delayed initiation and trials that are experiencing slow enrollment.

A new report uses lessons learned from the rapid development of COVID-19 vaccines to explore opportunities to overhaul R&D in the field, saying nothing in recent times has underlined the value of investing in basic research as much as the speedy development of effective vaccines.

COVID-19 vaccines are also a testament to the power of partnerships to break down institutional and competitive barriers to scientific collaboration, says the report by the high level Sabin-Aspen vaccine science & policy group. Such success can only become routine if there is a specific effort to bring people together across disciplines, to drive novel research.

To promote this convergence there should be support for a research infrastructure that creates opportunities for novel approaches and risk taking and leverages lessons from adjacent scientific areas, ranging from the chemistry and physics of vaccine formulation, to the immunological basis of protection.

In addition, clinical design is ripe for more efficient and nimbler approaches. Bringing together large datasets and analyses of clinical and laboratory information on infected and vaccinated individuals may make it possible to identify what level of immune response is needed to confer protection, allowing regulatory approval to be based on smaller and faster trials. The use of master protocols could accelerate trials and make it easier to compare the results of one study with those of another, the report says.

The effort to improve vaccine discovery and development and must be accompanied by updated regulatory science and processes, with streamlined preclinical testing, faster, nimbler and more cost-effective trials, and enhanced product scale-up and manufacturing, the group says.

The Danish Health Authority (DHA) said it would not use Johnson & Johnson’s single dose COVID-19 vaccine, following an evaluation by the European Medicines Agency which concluded there is a possible link between rare but severe cases of blood clots and the vaccine.

DHA said the COVID-19 epidemic in Denmark is currently under control and the vaccination rollout is progressing satisfactorily using other vaccines. As a result, it has decided the benefits of using the Johnson & Johnson vaccine do not outweigh the risk of causing serious blood clots.

The decision does mean there will be a four week delay in vaccinating people aged 20 – 39.

“In the midst of an epidemic, this has been a difficult decision to make, especially since we have also had to discontinue using the COVID-19 vaccine from AstraZeneca,” said DHA deputy director general, Helene Probst.

“Taking the present situation in Denmark into account, what we are currently losing in our effort to prevent severe illness from COVID-19 cannot outweigh the risk of causing possible side effects in the form of severe blood clots in those we vaccinate,” Probst said.

Denmark’s national vaccination rollout began more than four months ago and almost everyone in the most vulnerable group of people aged over 65 has been invited, has booked, or has begun the vaccination process.

The decision to continue the rollout without the COVID-19 vaccine from Johnson & Johnson will affect those between 20 and 39 years old, who are facing a delay of up to four weeks.

“Age is the main risk factor for severe illness from COVID-19, and these are younger citizens who are not at risk of becoming seriously ill," said Probst.

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