Novavax’s COVID Vaccine Shows High Efficacy In Trials; J&J One-Dose Shot Less So – As Europe Feuds With AstraZeneca Medicines & Vaccines 29/01/2021 • Madeleine Hoecklin Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Novavax’s vaccine candidate had a vaccine efficacy rate of 89.3%, while Johnson & Johnson’s highly anticipated single-dose COVID-19 vaccine is 66% effective in preventing moderate to severe infection. Novavax has become the first COVID-19 vaccine to show clinical efficacy against two major new SARS-CoV-2 virus variants now circulating worldwide – although the vaccine’s highest efficacy of 95.6% was against the COVID strain that had been predominant up until the end of 2020. The results of a UK-based Phase 3 clinical trial, which enrolled over 15,000 participants between 18 and 84 years of age, showed an efficacy rate of 85.6% for the Novavax vaccine against the B.1.1.7 variant first detected in the United Kingdom. Half of the COVID-19 cases in the trial were reportedly caused by the B.1.1.7 variant. The vaccine had a 60% efficacy rate against the “highly worrisome variant currently circulating in South Africa,” reported the principal investigator of the Novavax trial in South Africa, Professor Shabir Maddi. This left an average vaccine efficacy rate of 89.3% from the all arms of the trial. “[This] is the first vaccine to demonstrate not only high clinical efficacy against COVID-19 but also significant clinical efficacy against both the rapidly emerging UK and South Africa variants,” said Stanley C. Erck, CEO of Novavax, in a press release. Stanley C. Erck, President and CEO of Novavax, in an interview with CNBC. Meanwhile, the United States joined over 30 other countries in reporting infections from the B.1.351 variant (also called 501Y.V2), first identified in South Africa. Novavax’s results also included an analysis of a small Phase 2b trial in South Africa with 4,400 participants, where most of the cases that occurred were caused by the B.1.351 variant. Approximately a third of participants also were previously infected with SARS-CoV-2, which suggests that prior infection may not provide full immunity against the variant. Novavax Results Are First Showing Vaccine Efficacy Against Variants In Large Populations The Novavax results are the first to show vaccine efficacy against the variants in large clinical trials – as compared to lab tests of blood samples. While the vaccine performed less impressively against the variants – the results still are reassuring insofar as they pass the 60% bar that both the World Health Organization and the US Food and Drug Administration had set as a criteria for an effective COVID vaccine. “This is positive news and, if approved by the medicines regulator, the Novavax vaccine will be a significant boost to our vaccination programme and another weapon in our arsenal to beat this awful virus,” said Matt Hancock, UK Secretary of State for Health and Social Care. Other COVID-19 vaccines have only been tested on the variants in labs. Moderna announced on Monday that there was a six fold reduction in neutralizing antibodies with the B.1.351 variant, but suspected that the response would be sufficiently protective. Data from Pfizer’s in vitro studies on certain mutations present in the variants, released on Wednesday, revealed that neutralization against the virus was lower, but “the small differences in viral neutralization observed in these studies are unlikely to lead to a significant reduction in the effectiveness of the vaccine.” Novavax plans to immediately begin clinical development of a vaccine targeting the B.1.351 variant and expects to select a candidate for a booster or a combination bivalent vaccine in the coming days. Clinical testing on the new vaccines will commence between April and June of this year. “We can expect to see, if required, new vaccines or bivalent vaccines where two different strains are joined together in one vaccine. That now can be done at pace so that we can keep up with these variants, should they prove to be difficult to prevent with the vaccine that we have at the moment,” said Professor Paul Heath, Chief Investigator of the UK Novavax trial, in an interview with BBC Radio 4. The Novavax vaccine candidate, unlike the Pfizer/BioNTech and Moderna vaccines, uses fairly traditional vaccine technology to generate antigens derived from the SARS-CoV-2 spike protein, which are then joined with an adjuvant to enhance the immune response. Similar to the Oxford/AstraZeneca vaccine, it can be stored at normal refrigeration temperatures (2-8°C), which simplifies the transport and delivery process. “NVX-CoV2373 has the potential to play an important role in solving this global public health crisis. We look forward to continue to work…to make the vaccine available as quickly as possible,” said Erck. Novavax has signed vaccine deals with Canada for 75 million doses, the UK for 60 million doses, Australia for 51 million doses, New Zealand for 10.7 million doses, and the US for 100 million doses, which Operation Warp Speed paid US$1.6 billion to secure and to fund clinical development. Vaccination doses administered globally, as of 29 January 2021 since 14 December 2020. In addition, Novavax signed a manufacturing agreement with the Serum Institute of India to produce 1 billion doses of the vaccine in 2021, increasing the global manufacturing capacity to over 2 billion annually. Johnson & Johnson’s One-Shot Vaccine Shows Efficacy – But At Lower Levels On a less promising note, Johnson & Johnson’s highly anticipated single-dose COVID-19 vaccine was only 66% effective in preventing moderate to severe infection, according to results of Phase 3 trials released by the company on Friday. But that falls well behind the 90% or more efficacy ratings that Moderna and Pfizer/BioNTech vaccines have received – as well as the results obtained by Novavax and AstraZeneca in some arms of their trials. Among its 43,700 participants in the large J&J multi-country ENSEMBLE trial, the level of protection against moderate to severe infection provided by the vaccine varied by country and region, with the US recording an efficacy rate of 72%, Latin America reporting 66%, and South Africa recording the lowest levels of efficacy at 57%. The lower levels of protection in Latin America and South Africa could be due to the spread of SARS-CoV-2 variants that are more highly transmissible during the trial. Nearly all cases of COVID-19 in the trial in South Africa were linked to the variant, the company said. However it did not provide precisely stratified results against each individual variant. The company said that the Phase 3 ENSEMBLE clinical trial also showed “protection was generally consistent across race, age groups, including adults over 60 years of age.” Some 28 days after vaccination, the vaccine candidate was 85% effective in preventing severe disease – which includes admission to an intensive care unit, respiratory failure, organ failure, or death – in all adults over the age of 18 and in all regions studied. And complete protection against COVID-19-related hospitalization and death was provided by the vaccine candidate. Moderate illness was defined as COVID-19 infection with evidence of pneumonia, abnormal blood oxygen saturation levels, deep vein thrombosis, abnormal respiratory rate, or two or more systemic symptoms of COVID-19. A doctor administering the Johnson & Johnson COVID-19 vaccine candidate during the phase 3 clinical trials. J&J Touts Results On Severe Disease – Says It Will Still File For US FDA Authorization In February The company still plans to file for Emergency Use Authorization with the US Food and Drug Administration (FDA) in early February and expects to begin deploying doses immediately following its authorization. “These topline results with a single-shot COVID-19 vaccine candidate represent a promising moment,” said Paul Stoffels, Chief Scientific Officer at Johnson & Johnson, in a press release. “Eighty-five percent efficacy in preventing severe COVID-19 disease and prevention of COVID-19-related medical interventions will potentially protect hundreds of millions of people from serious and fatal outcomes of COVID-19. It also offers the hope of helping ease the huge burden placed on healthcare systems and communities.” The vaccine candidate can be stored for at least three months at temperatures of 2-8°C and can be transported using existing cold chain technologies and standard vaccine distribution channels. The logistical advantages of the Johnson & Johnson vaccine could prove instrumental in light of the increasing need to reduce transmission and the emergence of additional variants. “Changing the trajectory of the pandemic will require mass vaccination to create herd immunity, and a single-dose regimen with fast onset of protection and ease of delivery and storage provides a potential solution to reaching as many people as possible,” said Mathai Mammen, Global Head of Research and Development at Janssen Pharmaceuticals. “The ability to avoid hospitalizations and deaths would change the game in combating the pandemic.” J&J Also Signed Deal With COVAX Forecast of the vaccine candidate-specific supply of COVID-19 vaccines to the COVAX Facility, as of 20 January. Johnson & Johnson has also signed an agreement with the COVAX Facility to provide up to 500 million doses for distribution to low- and middle-income countries. Once the agreement is finalized, Gavi, the Vaccine Alliance, the organization co-leading COVAX, will be able to procure up to 200 million doses in 2021 and 300 million in 2022. Unfortunately, Johnson & Johnson is reportedly experiencing manufacturing delays and is lagging behind its previously set timeline. According to US federal government officials, the company is estimated to be two months behind schedule. The pharma company joins several others who have announced issues in vaccine production, a few of which, namely Pfizer, AstraZeneca and most recently Moderna, have delayed the delivery of doses. However, Johnson & Johnson claims to be on track to meet its contractual agreements. “The Company’s anticipated manufacturing timeline will enable it to meet its 2021 supply commitments, including those signed with governments and global organizations,” said the press release. AstraZeneca, Facing Clash with EU, Releases Vaccine Deal Meanwhile, AstraZeneca published its Advanced Purchase Agreement (APA) with the European Commission amid a feud over the delay in the delivery of COVID-19 vaccines to the region. The Advanced Purchase Agreement between AstraZeneca and the EU, signed on 27 August 2020. In the partially redacted contract, signed on 27 August, 2020, AstraZeneca committed to “use its Best Reasonable Efforts…to build capacity to manufacture 300 million doses of the vaccine…for distribution within the EU.” ‘Best Reasonable Efforts’ is defined as “the activities and degree of effort that a company of similar size with a similarly-sized infrastructure and similar resources as AstraZeneca would undertake or use in the development and manufacture of a vaccine at the relevant stage of development.” Since the UK holds its own deal directly with AstraZeneca and won’t face the same shortfall of vaccines, EU leaders have called for the delivery of doses produced in the UK to make up for the shortage. Pascal Soriot, CEO of AstraZeneca, claims that the products manufactured at the two plants in the UK are reserved for its own citizens under the vaccine deal until a sufficient number of doses have been supplied to the UK. EU officials, however, dispute this argument under article 5.4 of the contract, which states that AstraZeneca agrees to “use its Best Reasonable Efforts to manufacture the vaccine at manufacturing sites located within the EU…and may manufacture the vaccine in non-EU facilities.” According to Ursula von der Leyen, President of the European Commission, the pharmaceutical company is legally obligated to use the four manufacturing sites in Europe – two in the UK, one in Belgium, and one in the Netherlands – to fulfil its supply commitments. While the dispute remains unresolved, Spain and France have announced the temporary pause in their vaccine campaigns because of the shortage of doses. Madrid suspended inoculations on Wednesday for the next two week and Paris plans to temporarily halt its program beginning on 2 February. European Commission Establishes Authorization Mechanism for Vaccine Exports In a move to increase transparency surrounding the export of COVID-19 vaccines covered under APAs and to ensure the continuation of vaccination campaigns in the EU, the European Commission has put in place a measure requiring authorization for the export of vaccines produced in the EU. “We gave upfront funding to companies to build the necessary manufacturing capacity to produce vaccines, so deliveries can start as soon as they are authorised,” said Stella Kyriakides, Commissioner for Health and Food Safety, in a press release. “We now need transparency on where the vaccines we secured are going and ensure that they reach our citizens.” Stella Kyriakides, European Commissioner for Health and Food Safety, at a press briefing on Friday. The “time-limited and targeted system” will be in place until the end of March 2021 and will not interfere with the EU’s humanitarian aid commitments, including the delivery of vaccines to low- and middle-income countries through the COVAX Facility, according to Valdis Dombrovskis, Executive Vice-President and Commissioner for Trade of the European Commission. The authorization will be granted or denied by the EU member states where the production of COVID-19 vaccines takes place. The aim of the new measure will not be to restrict exports “any more than absolutely necessary,” but instead to ensure the critical shortages in Europe are relieved in a “targeted, transparent, proportionate, [and] temporary” manner, said the trade document published by the European Commission on Friday. AstraZeneca Vaccine Receives Approval from EU Regulator Hours earlier, the European Medicines Agency (EMA) recommended the Oxford/AstraZeneca vaccine for approval one month after the UK provided it with authorization and began the vaccine rollout. The European Commission followed suit shortly after and granted conditional marketing authorization to the vaccine on Friday, making it the third COVID-19 vaccine authorized in the EU. After much discussion about whether the vaccine rollout should include adults over the age of 55, due to the lack of data in older participants, the EMA decided to recommend the vaccine to individuals aged 18 and older. “There are not yet enough results in older participants…to provide a figure for how well the vaccine will work in this group. However, protection is expected, given that an immune response is seen in this age group and based on experience with other vaccines…EMA’s scientific experts considered that the vaccine can be used in older adults,” said the EMA press release. Overall, the vaccine demonstrated a 60% efficacy rate in clinical trials. “With the AstraZeneca vaccine now authorized, 400 million additional doses will be available in Europe. I expect the company to deliver these doses as agreed, so that Europeans can be vaccinated as soon as possible,” said Ursula von der Leyen, President of the European Commission in a press release. We have just authorised the @AstraZeneca vaccine on the EU market following a positive assessment by @EMA_News I expect the company to deliver the 400 million doses as agreed. We will keep on doing all we can to secure vaccines for Europeans, our neighbours & partners worldwide — Ursula von der Leyen (@vonderleyen) January 29, 2021 Following news of the authorization of the Oxford/AstraZeneca vaccine in the EU, WHO officials expressed their hope to grant the vaccine emergency use listing within two weeks. The Strategic Advisory Group of Experts on Immunisation (SAGE), WHO’s vaccine advisory panel, is scheduled to meet to review the Oxford/AstraZeneca vaccine on 8 February. “We should have an emergency use listing, providing, of course, that everything goes to plan and all the data is there. We can then start receiving doses from the manufacturing sites in India and South Korea,” said Soumya Swaminathan, WHO Chief Scientist, at a press conference on Friday. The Oxford/AstraZeneca vaccine is considered one with global potential – due to its ability to be stored at refrigerator temperatures, making its storage and transportation more manageable, particularly for countries without access to ultra-cold chain storage, which is required for the Pfizer and Moderna vaccines. Status of COVID-19 vaccines in the process of receiving WHO “Emergency Use Listing” approval, as of 25 January. Image Credits: Johnson & Johnson, Johnson & Johnson, CNBC, Our World in Data, Johnson & Johnson, GAVI, European Commission, Twitter – European Commission, WHO. Share this:Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window) Combat the infodemic in health information and support health policy reporting from the global South. 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