Johnson & Johnson said it has temporarily paused further dosing in all its COVID-19 vaccine trials, including the phase III trial that began on 23 September, due to an unexplained illness in a study participant. The participant’s illness is being reviewed and evaluated by the independent safety monitoring board and the company’s physicians.
There are no details on the nature of the unexpected illness. Johnson & Johnson said adverse events are not uncommon in clinical trials, and the number can reasonably be expected to increase in trials involving large numbers of participants. Also, as many trials are placebo-controlled, it is not always immediately apparent whether a participant received a study treatment or a placebo.
The start of the phase III trial followed positive interim results from the phase I/II clinical study, which demonstrated the safety profile and immunogenicity after a single vaccination were supportive of further development. Based on these results, the phase III is due to enrol up to 60,000 volunteers.
As the phase III began, Johnson & Johnson said it has continued the scaling up of its manufacturing capacity and remains on track to meet the goal of providing one billion doses of a vaccine each year.
AstraZeneca said it ready to start phase clinical development of AZD7442, a long-acting combination of two COVID-19 antibodies.
One study, in 5,000 participants, will evaluate if AZD7442 is able to prevent COVID-19 infection, while a second trial will see if it is effective in preventing serious disease in 1,100 people post-exposure to the virus.
The US government will invest up to $486 million for the trials, and for the supply of up to 100,000 doses, with the option to acquire another one million doses.
AZD7442 is based on antibodies discovered by scientists at Vanderbilt University in the blood of patients who recovered from COVID-19. AstraZeneca has engineered the antibodies to be long-acting, with the therapeutic effect expected to last for 6 – 12 months after a single administration.
The product is intended to mimic the natural antibodies and has the potential to treat and prevent disease progression in patients already infected with the virus, as well as to be given as a preventative prior to exposure to the virus. The combination of two antibodies is intended to maintain effectiveness if the SARS-CoV-2 virus develops resistance to one of the pair.
Research commissioner Mariya Gabriel said that after initially testing negative for COVID-19, a second test turned out to be positive on Saturday.
Gabriel has been in self-isolation since 5 October, when a member of her staff tested positive for COVID-19. She and her team are working from home. “I have been in self-isolation since Monday and continue staying at home, following the established regulations,” Gabriel said.
Following her announcement, the European Commission has come up with new rules for internal meetings. Special meetings of commissioners’ heads of cabinet will be held online, and no other staff will be allowed at their weekly physical meeting. Commissioners will be able to join the college meeting only if they test negative.
The commission sealed a contract with Janssen Pharmaceutica for member states to purchase 200 million doses of the company’s COVID-19 vaccine, in the third such advance purchase agreement.
The commission has already signed contracts with AstraZeneca and Sanofi/GlaxoSmithKline, and has successfully concluded talks with German biotechs CureVac and BioNTech, and with US company Moderna.
Health commissioner Stella Kyriakides said the Janssen deal increases the chances the EU will have access to an effective vaccine. “More agreements will follow, and we remain determined in our search for a successful and safe vaccine to combat this deadly pandemic,” she said.
Janssen’s COVID-19 vaccine uses the AdVac technology platform that was used to develop and manufacture the company’s recently approved Ebola virus vaccine. The COVID-19 vaccine is in phase III clinical trials.
In return for the right to buy a specified number of vaccine doses in a given timeframe, the commission finances part of manufacturers’ upfront costs through advance purchase agreements, that subsequently act as down-payments on the vaccines when they are purchased by member states.
The high cost and high failure rate make investing in COVID-19 vaccines high-risk. The commission says the advance purchase agreements will allow investments to be made that otherwise would probably not happen.
The commission has signed a procurement agreement with US biotech Gilead Sciences, which it says will enable rapid and equitable access to Veklury (remdesivir), the first antiviral drug to have been shown to be effective in treating COVID-19.
The agreement removes the need for Gilead to negotiate country-by-country reimbursement arrangements. It will allow member states, the UK and countries in the European Economic Area, to purchase Veklury for immediate use and for stockpiling, over the next six months, and has the option to be extended.
Gilead said it will begin fulfilling orders in the week of October 12. The procurement agreement replaces an emergency support instrument through which the European Commission procured Veklury from August - October 2020.
The European Commission granted conditional marketing authorisation for Veklury on 3 July 2020, based on data from a randomised, double blind, placebo controlled trial that demonstrated efficacy and safety in COVID-19 patients with pneumonia who needed oxygen.
Supply of Veklury is expected to meet global demand by the end of this month, enabling the purchase of the drug both to treat patients and to support national stockpiling for current and future surges of COVID-19 infections.
The European Commission announced it has approved a €61 million state aid programme for Lithuania, supporting research, development and manufacturing of products to help fight the COVID-19 pandemic.
Companies of all sizes will receive grant funding of up to 80 per cent of costs for R&D and manufacture of vaccines, ventilators, protective clothing and equipment, diagnostic tools and disinfectants, and for data collection/processing tools.
The annual 3M State of Science Index (SOSI) shows that the image of science is on the up, with trust in science and scientists the highest it has been in three years since SOSI first began.
Today, 89 per cent of those surveyed trust science; 86 per cent trust scientists; 77 per cent are more likely as a result of the pandemic to agree that science needs more funding; and 54 per cent agree science is very important to their everyday lives, compared to 44 per cent pre-pandemic.
Rounding out the picture, 92 per cent of respondents believe actions should follow science to contain the global pandemic, another measure of trust in science.
And a world that has been increasingly sceptical of science seems to be waking up to its relevance and importance. In 2020, the level of scepticism reversed for the first time in three years. People who stated, “I am sceptical of science,” dropped to 28 per cent during the pandemic, from 35 per cent last year.
German biotech BioNTech and pharma partner Pfizer Inc announced the initiation of a rolling submission to the European Medicines Agency (EMA) for BNT162b2, the lead candidate in their COVID-19 vaccines programme. The EMA’s decision to start a rolling review follows preliminary results from preclinical and early clinical studies in adults, which suggest the vaccine triggers both an innate and adaptive immune response, prompting production of neutralising antibodies and T cells.
As part of the rolling review, EMA has begun evaluating data generated in preclinical research. “It is our duty to ensure that while we are working to develop a potential vaccine at unprecedented speed to help address this pandemic, we do so with the highest ethical standards while adhering to sound scientific principles. We will continue to have regular and open dialogue with the EMA throughout the rolling review process,” said Ugur Sahin, CEO and co-founder of BioNTech.
BNT162b2 is currently being evaluated in a global phase III study at more than 120 clinical sites worldwide, including the US, Brazil, South Africa and Argentina. To date, the trial has enrolled approximately 37,000 participants with more than 28,000 having received their second vaccination.
Preliminary data from phase I/II studies demonstrated BNT162b2 is well tolerated, with mild to moderate adverse events in all age groups. The vaccine candidate generated dose level-dependent immunogenicity.
Normally, all preclinical and clinical trial data is submitted to EMA in one file once development is completed. In the case of a rolling review, EMA reviews data as they become available.
As the large scale phase III trial of the Coronavac COVID-19 vaccine developed by Chinese pharma Sinovac Life Science continues in Brazil, the state of Sao Paulo has signed a contract for 60 million doses. Of these, six million doses are to be supplied ready for use, in October, while a further 40 million will be delivered for fill and finish at the Butantan Institute, one of Brazil’s leading biomedical research centers. Sinovac guaranteed the state of Sao Paulo an additional 14 million doses by February 2021.
The contract also allows for technology for manufacturing the vaccine to be transferred to the Butantan Institute, and for local production to begin next year.
Coronavac is currently in a 13,000 subject phase III trial at 16 research centres across Brazil. To date 7,000 volunteers have received one of two doses
Last Friday, preliminary data for Coronavac were submitted to Anvisa, the National Agency for Health Safety (Agência Nacional de Vigilância Sanitária), as part of a rolling review to speed approval if the vaccine is shown to be safe and effective in the phase III trial.
The European Medicines Agency says there is a need to prepare for a sharp rise in applications for approvals of COVID-19 therapeutics and vaccines between now and the middle of next year. It has invoked its business continuity plan to cope with the initial wave of COVID-19-related work, which will impact its other activities.
The agency said it is already diverting resources away from other important European public health activities and additional resources are also required for communication activities and engagement with stakeholders on vaccines. The board of EMA stressed it is critical that extra resources are urgently made available to allow the agency to fulfil its public health mandate and respond to patient needs in all disease areas.
The pandemic hit at a time when EMA was already working under stress and with work on hold following its relocation from London to Amsterdam last year. In addition to losing 25 percent of its 890-strong workforce who elected not to make the move to Amsterdam, EMA lost access to experts in the UK’s Medicines and Healthcare products Agency.
The problems facing the agency were discussed at the October 2020 meeting of its management board, the last to take place before Guido Rasi, EMA’s executive director hands over to Emer Cooke in mid-November.
The board also discussed safeguards to secure the robustness and independence of the scientific review process for approvals for COVID-19 therapeutics and vaccines. Rasi has now sent a response to a recent enquiry from the European Ombudsman, noting measures have been introduced to ensure that the scientific review process of applications for COVID-19 vaccines and the EU vaccine purchasing procedure under the advance purchasing agreements remain separate processes. This means, for instance, that scientific committee members and experts involved in the licensing procedures cannot take part in the EU advance purchasing procedures and vice versa.