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

GlaxoSmithKline (GSK) announced it will carry out fill and finish of up to 60 million doses of the COVID-19 vaccine developed by the US biotech Novavax that have been ordered by the UK government.

GSK will provide capacity at its facility in Barnard Castle in north east England, from May 2021, with rapid technology transfer between the two companies beginning immediately, the pharma company said on Monday.

The raw material for the Novavax vaccine is also produced in the region, by Novavax manufacturing partner, Fujifilm Diosynth Biotechnologies, at its site in Billingham.

The UK government has ordered 60 million doses of the vaccine under an advance purchase agreement with Novavax.

The UK Vaccine Taskforce has played a key role in enabling production of the Novavax vaccine in Europe, supporting clinical trials and manufacturing, and now arranging for GSK to do fill and finish.

Health minister Matt Hancock said, “We've all seen just how important onshore vaccine manufacturing capabilities are, and this fantastic deal will ensure more of these vital products can be produced here in the UK. The UK’s vaccination programme has been a national success, with over 30 million people now having received a first dose of a COVID-19 vaccine.”

The Novavax product has shown strong potential efficacy in phase III clinical trials, including against the B.1.1.7 variant of concern that is driving a third wave of infections in Europe.  

It is expected Novavax will apply for approval from the UK Medicines and Healthcare products Agency during the next three months.

Following unprecedented public criticism from the US National Institute of Allergy and Infectious Diseases that the interim results of the US phase III trial of its COVID-19 vaccine published on Monday, were “outdated” AstraZeneca has rushed to complete the full primary analysis.

The results, published this morning  show the vaccine has 76% efficacy in preventing symptomatic COVID-19 infections.

That is 3% lower than in the interim analysis, but is consistent with the interim result, given the range of possible values (confidence interval) of 68% to 82%.

AstraZeneca said the results have been presented to independent experts monitoring the trial who raised the concern that the data presented on Monday were incomplete. The primary analysis is pre-specified in the trial protocol and will be the basis for the company to apply for US Food and Drug Administration approval in the coming weeks, the company said.

Mene Pangalos, executive vice president of BioPharmaceuticals R&D at AstraZeneca said, "The primary analysis is consistent with our previously released interim analysis, and confirms that our COVID-19 vaccine is highly effective in adults, including those aged 65 years and over. We look forward to filing our regulatory submission for emergency use authorisation in the US and preparing for the rollout of millions of doses across America."

Results of the AstraZeneca US phase III trial of AZD1222, released this morning, show statistically significant vaccine efficacy of 79% in preventing symptomatic COVID-19 infections and 100% efficacy at preventing severe disease and hospitalisation.

The interim safety and efficacy analysis is based on 32,449 participants, in whom there were 141 symptomatic cases of COVID-19. The trial had a 2:1 randomisation of vaccine to placebo.

Vaccine efficacy was consistent across ethnicity and age. Notably, in participants aged 65 years and over, vaccine efficacy was 80%.

The vaccine was well tolerated, and the independent data safety monitoring board did not identify any safety concerns related to the vaccine. This included a specific review of blood clots and the more serious cerebral venous sinus thrombosis, which caused use of the vaccine to be suspended in Europe earlier this month.

Ann Falsey, professor of medicine at University of Rochester School of Medicine, who is co-lead principal investigator for the trial, said the findings reconfirm previous results. “This analysis validates the AstraZeneca COVID-19 vaccine as a much-needed additional vaccination option, offering confidence that adults of all ages can benefit from protection against the virus.”

Mene Pangalos, executive vice president of biopharmaceuticals R&D at AstraZeneca said the results add to the growing body of evidence showing the vaccine is well tolerated and highly effective against all severities of COVID-19 and across all age groups. “We are preparing to submit these findings to the US Food and Drug Administration and for the rollout of millions of doses across America should the vaccine be granted US emergency use authorisation,” he said.

The safety committee of the European Medicines Agency said the benefits of AstraZeneca’s vaccine in combating the still widespread threat of COVID-19 infection continue to outweigh the risk of side effects.

The vaccine is not associated with an increase in the overall risk of blood clots (venous thrombosis), while COVID-19 infection itself results in clotting problems that may be fatal. Overall, the number of thromboembolic events reported after vaccination, both in clinical trials before approval and after rollout of vaccination campaigns, was lower than that expected in the general population, EMA said.

There is also no evidence of a problem related to specific batches of the vaccine, or to particular manufacturing sites.

However, there remains a question over whether the vaccine may be associated with some very rare cases of specific types of thromboses. While around 20 million people in the EU and UK had received the AstraZeneca vaccine as of March 16, EMA has received reports of 25 such cases. The safety committee said a causal link with the vaccine is not proven, but on the basis of available evidence could not rule out a connection, and it will now carry out further analyses.

A warning about the possibility of rare clotting disorders will be added to the label on the vaccine and the patient information leaflet, but the safety committee said the vaccine’s proven efficacy in preventing hospitalisation and death from COVID-19 outweighs the extremely small likelihood of serious thromboses.

Germany, France, Italy and other EU countries that stopped using the AstraZeneca vaccine pending the safety review said they would resume its use.

Sewage monitoring needs to be included in national testing programmes for tracking SARS-CoV-2, as part of an update of testing strategies to detect mutated variants of the virus that may be more transmissible and/or cause more serious disease.

EU funding will be made available to support deployment, the analysis samples for the presence of variants and for the exchange of data, to inform preparedness and response measures.

The monitoring systems, to be in place no later than October 2021, should include all towns and cities with populations greater than 150,000, with minimum sampling frequencies of twice a week. The initiative is part of a common path to safe and sustained ending of lockdown measures published by the Commission on Wednesday.

The Commission is to set out a common EU strategy on COVID-19 therapeutics in mid-April, to parallel the approach it used to promote vaccines research and procurement.

The move was announced as part of a common path to safe and sustained lifting of COVID-19 lockdown measures across the EU, published on Wednesday.

Currently, a number of instruments including joint procurement, are being used to secure access for member states to the limited number of drugs that are available to treat COVID-19 infections. But the Commission says, “More and faster action is needed.” The aim of the strategy will be to speed up research and manufacturing.

There will also be more flexibility around drug regulation to enable rapid supply at large scale during the pandemic.

As part of its support for member states in the fight against COVID-19, the European Commission is purchasing 200 ultraviolet light disinfecting robots, for delivery to hospitals around Europe during 2021.

The robots can disinfect a standard size patient room in as little as 10 minutes and can clean more than 18 rooms on one charge. This will help ensure a sterile environment in hospitals, without exposing staff to unnecessary risk.

The €12 million programme got underway following a study by researchers from the European Society of Clinical Microbiology and Infectious Diseases looking at the feasibility of deploying the robots, which was published last month.

This concluded disinfection robots have already been shown to be a promising tool for surface decontamination in hospitals, with even greater potential to come. Adjustments to both hospitals and devices are needed to allow the free movement of robots. More research is required to define effective wavelengths and exposure times, to allow sufficient energy to be applied to each surface, as a function of which pathogen is to be inactivated.

The European Medicines Agency’s safety committee is meeting on Tuesday to review data on AstraZeneca’s COVID-19 vaccine after several member states suspended its use following reports of blood clots in people who received the vaccine.

EMA said it is working with the company, experts in blood disorders and other health authorities. These include the UK Medicines and Healthcare products Agency, cut out of EMA as a result of Brexit, but now sitting on a large safety database, with around 11 million doses of the vaccine administered in the UK to date, and few reports of serious adverse events.

Meanwhile, in an attempt to fill the gap, Pfizer and BioNTech have agreed with the European Commission to accelerate delivery of ten million doses of their vaccine between April and June.

Commission President Ursula von der Leyen said, “These accelerated ten million doses will bring the total doses of Pfizer/BioNTech in quarter two up to over 200 million.” This gives member states room to manoeuvre, she said.

These doses will be drawn forward from the 100 million doses that were due to be delivered in Q3 and Q4 of 2021. 

EMA said its experts are looking in great detail at all the available data and clinical circumstances surrounding specific cases to determine whether the AstraZeneca vaccine might have contributed, or if blood clots could have been due to other causes. After reviewing the data today, EMA has called a meeting on Thursday to decide on any further action.

While it investigates, EMA said it currently remains of the view that, “The benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalisation and death, outweigh the risks of side effects.”

More than 300 COVID-19 machine learning models were described in papers published in 2020 but none is suitable for detecting or diagnosing COVID-19 from standard medical imaging, due to biases, methodological flaws, lack of reproducibility, and inappropriate datasets, according to a systematic review.

Researchers led by Cambridge University reviewed 2,212 studies published between 1 January and 3 October 2020, describing machine learning models that claimed to be able to diagnose or predict the severity of COVID-19 from chest Xrays or computed tomography images.

After quality screening, 62 studies were included in the systematic review. None of the 62 models was of potential clinical use, according to results reported in Nature Machine Intelligence.

“Any machine learning algorithm is only as good as the data it's trained on,” said first author Michael Roberts from the department of applied mathematics at Cambridge University. "Especially for a brand-new disease like COVID-19, it's vital that the training data [are] as diverse as possible because, as we've seen throughout this pandemic, there are many different factors that affect what the disease looks like and how it behaves."

The European Medicines Agency has recommended approval of Johnson & Johnson’s single dose COVID-19 vaccine.

“With this latest positive opinion, authorities across the EU will have another option to combat the pandemic and protect the lives and health of their citizens,” said Emer Cooke, EMA’s Executive Director. “This is the first vaccine which can be used as a single dose.”

Results from a clinical trial involving 44,000 people in the US, South Africa and Latin American countries found there was a 67% reduction in the number of symptomatic COVID-19 cases after two weeks in people who received the vaccine (116 cases out of 19,630 people), compared with people given placebo (348 of 19,691 people).

The vaccine is already approved in the US.