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

US biotech Novavax has received EU marketing approval for COVID-19 vaccine Nuvaxovid, which becomes the fifth vaccine approved by the European Medicines Agency.

The approval is based on results from two main clinical trials involving over 45,000 people.

The first study, conducted in Mexico and the US, found a 90.4% reduction in the number of symptomatic COVID-19 cases from 7 days after the second dose in people who received Nuvaxovid (14 cases out of 17,312 people), compared with people given placebo (63 out of 8,140 people)..

The second study conducted in the UK also showed a similar reduction in the number of symptomatic COVID-19 cases in people who received Nuvaxovid (10 cases out of 7,020 people), compared with people given placebo (96 out of 7,019 people). In this study, the vaccine efficacy was 89.7%.

Taken together, the results of the two studies show a vaccine efficacy for Nuvaxovid of around 90%. The original strain of SARS-CoV-2 and the Alpha and Beta variants of concern were the most common viral strains circulating when the studies were ongoing. There is currently limited data on the efficacy of Nuvaxovid against the Omicron variant which is now spreading rapidly across Europe.

Nuvaxovid contains a synthetic version of the spike protein found on the surface of SARS-CoV-2, along with an adjuvant to help strengthen immune responses to the vaccine.

A new study based on real world evidence from Scotland and Brazil suggests that booster programmes are needed to help maintain protection from severe disease in those vaccinated with AstraZeneca’s vaccine.

The researchers analysed data from two million people in Scotland and 42 million people in Brazil. They found that in Scotland, when compared with two weeks after receiving a second dose, there was approximately a fivefold increase in the chance of being hospitalised or dying from COVID-19 at around five months after being double vaccinated.

The decline in effectiveness begins to first appear at around three months, when the risk of hospitalisation and death is double that of two weeks after the second dose. Similar numbers were seen for Brazil.

The researchers were able to compare data between Scotland and Brazil as they had a similar interval between doses, of 12 weeks, and the same initial prioritisation of who was vaccinated – people at highest risk of severe disease and healthcare workers.

The dominant variant was different in each country during the study period – Delta in Scotland and Gamma in Brazil – meaning the decline in effectiveness is likely because of vaccine waning and the impact of variants, the researchers say.

The study also estimated vaccine effectiveness at fortnightly intervals by comparing outcomes of people who have been vaccinated with those who are unvaccinated.

Aziz Sheikh, director of Edinburgh University’s Usher Institute and study lead, said, “Vaccines have been a key tool in fighting the pandemic, but waning in their effectiveness has been a concern for a while. By identifying when waning first starts to occur in the AstraZeneca vaccine, it should be possible for governments to design booster programmes that can ensure maximum protection is maintained.”

Scientists at the Universidad Carlos III de Madrid have developed the first photo-electrochemical sensor that can detect the SARS-CoV-2 virus in a saliva sample. This sensor, which uses a type of artificial antibody called an aptamer, is claimed to be more sensitive that antigen-based sensors and to detect the virus more quickly and cheaply than PCR tests.

These new sensors can be incorporated into portable diagnostic systems and are easy to use.

The researchers say the sensor has a wide range of sensitivity to different virus concentrations, meaning it is capable of detecting concentrations below 0.5 nanomolar, that is typical in patients who have not yet developed COVID symptoms. It works at concentrations of up to 32 nanomolar, providing a tool for monitoring the progress of infection in patients.

“The advantage over current antigen-based sensors is the greater sensitivity and specificity of the photo-electrochemical sensor measurements, which are comparable to more complex measurements, such as those from fluorescence-based sensors, and they are simpler, cheaper, and faster than PCR-based sensors,” said Mahmoud Amouzadeh Tabrizi, researcher at the university’s Department of Electronic Technology.

This research is being undertaken as part of a project financed by the Regional Government of Madrid and the EU, which brings together scientists from the Madrid region to develop technologies for manufacturing tissue and organs, and to optimise these processes for clinical and industrial application.

A single booster dose of the COVID-19 vaccine being co-developed by Sanofi and GlaxoSmithKline delivered consistently strong immune responses, with neutralising antibodies increasing 9- to 43-fold regardless of the primary vaccine received (AstraZeneca, Johnson & Johnson, Moderna, Pfizer/BioNTech), and for all age groups tested.

The companies said the booster was well tolerated, with a safety profile similar to currently approved COVID-19 vaccines.

However, the ongoing global phase III trial to support approval of the vaccine has been extended into early 2022, in order to accrue more data. That is because at this stage in the pandemic it has been hard to recruit enough people who were infection naïve and had never been infected by SARS-CoV-2, as required by the regulators.

“These preliminary data show we have a strong booster candidate, whatever primary vaccine you have received,” said Thomas Triomphe, executive vice president, Sanofi Pasteur. “While pursuing a phase III trial is a challenge in a quickly shifting pandemic environment, we look forward to seeing the results to support submissions of our booster vaccine as quickly as possible.”

The booster trial is ongoing across sites in multiple countries, including the US, France, and the UK, and is now assessing how effective the vaccine is against the Omicron variant of concern.

The clinical development is being funded by the US Biomedical Advanced Research and Development Authority.

Treatments for multiple sclerosis (MS) can reduce the effectiveness of COVID-19 vaccines, according to researchers from Cardiff University and Queen Mary University of London.

Disease-modifying MS drugs affect the immune system, and as vaccines work by triggering the body to produce an immune response, it was suspected this might happen.

The researchers studied almost 500 people with MS. Their findings show that those taking two particular drugs, fingolimod and ocrelizumab, were less likely to produce antibodies in response to AstraZeneca and Pfizer/BioNTech COVID-19 vaccines than people with MS not taking these disease modifying drugs.

The researchers also studied T-cell responses in a small group of study participants who failed to mount an adequate antibody response to COVID-19 vaccination. They found that overall, 40% of this group were able to produce a strong T-cell response.

“People with MS have faced uncertainty during the Covid-19 pandemic as a direct result of their condition and the treatments they take to manage it,” said Ruth Dobson, clinical senior lecturer in neurology at Queen Mary. “Our study provides high-quality evidence that will support clinicians to advise people with MS on treatment options. However, further trials are essential to help us understand how best to balance the risks of potentially suspending or delaying MS treatment with the need to effectively vaccinate people with MS against COVID-19,” she said.

Oxford University is getting £50 million from India’s largest vaccines manufacturers, Serum Life Sciences, to set up a new vaccines research laboratory.

The lab will be built on the same site as the recently announced Oxford University Pandemic Sciences Centre, with the buildings sharing infrastructure and support facilities.

 The Serum-funded facility will house over 300 research scientists and will provide the focus and scale for translation of the university’s academic vaccine development programmes.

The new building will house the headquarters and main laboratory space of the Jenner Institute, which collaborated with Serum on the development and global rollout of AstraZeneca’s COVID-19 vaccine, which is based on research carried out at the university. The two are also collaborating on the development of a malaria vaccine.

 Adrian Hill, director of the Jenner Institute, said the success of the collaborative programmes on both the malaria and COVID-19 vaccines, “Has highlighted the great potential of partnerships between leading universities and large-scale manufacturers to develop and supply vaccines for very cost-effective deployment at exceptional scale. We look forward to a wider range of vaccine activities in the future, building on this generous support.”

Researchers from Oxford University have analysed the impact of the Omicron COVID-19 variant of concern on the immune responses generated by vaccination using blood samples from individuals who had previously received two doses of the AstraZeneca or Pfizer/BioNTech vaccines.

They show there was a substantial decrease in the level of neutralising antibodies generated in response to vaccination against, or infection from, COVID-19.

The results indicate that the Omicron variant has the potential to drive a further wave of infections, including among those already vaccinated, the researchers say, though they highlight that there is currently no evidence of increased potential to cause severe disease, hospitalisations or death.

Gavin Screaton, head of the Medical Sciences Division at Oxford University, who led the research said, “These data will help those developing vaccines, and vaccination strategies, to determine the routes to best protect their populations, and press home the message that those who are offered booster vaccination should take it.”

Matthew Snape, professor in paediatrics and vaccinology, said, “These data are important but are only one part of the picture. They only look at neutralising antibodies after the second dose, but do not tell us about cellular immunity.”

The next step for the research will be to use the stored blood samples to assess the impact of booster doses

Following an interim recommendation to support governments in deciding on early use of Merck’s COVID-19 antiviral drug Lagevrio, the European Medicines Agency is now reviewing more data from the main clinical study.

The interim recommendation was based on an assessment of data based on 762 subjects. This showed Lagevrio reduced the risk of hospitalisation or death in people with COVID-19 who were at higher risk of severe disease from 14.1% in the placebo group to 7.3% in the Lagevrio group. The study did not include people who had been vaccinated.

The updated results, based on 1,408 subjects, show that Lagevrio reduced the risk of hospitalisation or death in people with COVID-19 who were at higher risk of severe disease from 9.7% in the placebo group to 6.8% in the Lagevrio group.

EMA said it will assess these data as part of the review of the marketing application, but for now the earlier recommendations remain unchanged.

Lagevrio is an oral drug that reduces the ability of SARS-CoV-2 to multiply in the body by increasing the number of mutations in its genetic material, impairing the ability of the virus to multiply.

Apogenix announced it has received €20.7 million funding from the German Federal Ministries of Health (BMG) and of Education and Research (BMBF), as part of the ‘Clinical development of COVID-19 drugs and their manufacturing’ programme.

The money will be used to finance a phase III clinical trial of Apogenix’s drug asunercept in moderately to severely ill, hospitalised COVID-19 patients and for scaling up its manufacturing.

The German government will fund 80% of these costs, and the remaining 20% will be covered by Apogenix’s main investor dievini Hopp BioTech Holding.

Interim data from an ongoing phase II trial in the treatment of moderately to severely ill COVID-19 patients has provided initial evidence of the efficacy. It is thought asunercept has the potential to treat severely ill COVID-19 patients irrespective of the SARS-CoV2 virus variants.

“It is becoming more and more evident that, in addition to COVID-19 vaccines, there is an urgent need for effective drugs to treat those who develop COVID-19 without or despite vaccination,” said Thomas Hoeger, CEO of Apogenix. Asunercept is expected to prevent the death of immune cells and lung cells that leads to acute respiratory distress syndrome, thus reducing the number of COVID-19 patients who require intensive care.

The phase III trial will recruit hospitalised COVID-19 patients with advanced disease who are being treated with oxygen in addition to standard therapy.

The UK Health Security Agency (UKHSA) has published an updated risk assessment for the Omicron variant, that suggests this new form of the SARS-CoV-2 virus is displaying a significant growth advantage over Delta, meaning that it is likely to outcompete Delta in the UK and become the dominant variant.

The assessment is based on analysis of UK data showing increased household transmission risk, increased secondary attack rates - that is the chance of each case infecting another individual - and increased growth rates compared to Delta.

If the growth rate and doubling time continue at the rate seen in the last two weeks since the existence of Omicron was first announced by scientists in South Africa, it is expected at least 50% of COVID-19 cases to be caused by the Omicron variant in the next 2-4 weeks. The UK recorded 51,342 cases of COVID-19 on Wednesday 8 December.

The risk assessment also suggests that Omicron reduces the level of protection given by having had a previous infection or vaccination. Whilst there are insufficient data to quantify either vaccine effectiveness or risk of reinfection in the UK exactly, the observed growth, case distribution and early analyses in both South Africa and the UK are consistent with some loss of immune protection against infection. UKHSA said new studies are being undertaken to assess this further.

As yet, there are insufficient data to make any assessment of protection against severe disease, or to assess the severity of illness caused by Omicron. Further studies are underway in the UK and abroad.

One of the reasons for the gap in the data is that only half of the PCR tests are able to detect Omicron. This gap is being filled by sending 15 – 20% of all PCR tests samples for genomic sequencing.

UKHSA’s chief medical advisor, Susan Hopkins said, “It is increasingly evident that Omicron is highly infectious and there is emerging laboratory and early clinical evidence to suggest that both vaccine-acquired and naturally acquired immunity against infection is reduced for this variant.”

Since the emergence of SARS-CoV-2 virus and its global spread, the UK has sequenced and shared more than 1.4 million genomes. It has been gradually increasing sequencing capacity since March 2021 with the weekly upload of sequences increasing from 20,000 genomes per week to 64,000 last week and it will be closer to 80,000 by January 2022.