Coronavirus Update: Oxford Racing Ahead With 8,000 Vaccinated In Phase III Trial
Plus: Eisai Joins RE-MAP Cap Study
Executive Summary
Partnering with AstraZeneca, the Oxford team has opened up a clear lead in the race to enrol thousands of patients for late-stage safety and efficacy trials – but cannot make guarantees of when results might be ready.
Oxford Racing Ahead With 8,000 Vaccinated In Phase III Trial
The University of Oxford team developing a coronavirus vaccine with AstraZeneca PLC is well ahead in the race to conduct late-stage trials, with 8,000 volunteers already dosed in its Phase III study.
This puts it far in advance of other frontrunners such as Moderna Inc. and Pfizer Inc., who are yet to begin their Phase III trials.
The candidate, known as AZD1222, was identified last week as the clear leader in terms of its progress through clinical studies by the World Health Organization (WHO), and the trial’s lead investigator has now shared details of its rapid development.
Professor Sarah Gilbert, professor of vaccinology at Oxford Jenner Institute, and co-developer of the adenovirus-based vaccine, gave evidence to the UK parliamentary House of Commons Science and Technology committee on 1 July, alongside other leaders in the country’s life science sector spearheading COVID-19 vaccines and therapeutics development.
Professor Sarah Gilbert
Gilbert said: “We now have 8,000 people vaccinated in the phase three trial in the UK, that's very good going. Apart from the ability to test efficacy ... that also gives us the safety database that we need, because we're looking at the vaccine in older adults as well as younger adults. We need safety data and we need to look at the immune response in people of different ages as well.”
The declining prevalence of COVID-19 in the UK has meant the researchers have widened their net to other countries where the infection rates are still high. The Oxford team has signed agreements with researchers in South Africa and Brazil, and has already dosed several hundred volunteers in Brazil.
Gilbert said this would soon rise to 4,000 in Brazil and a further 2,000 in South Africa, with AstraZeneca commencing a study of up to 30,000 people in the US in August.
Also giving evidence to the parliamentary committee was Kate Bingham, an experienced venture capital executive at SV Health Ventures who has been drafted in by the UK government to spearhead national efforts to develop a coronavirus vaccine.
She was careful not to make any predictions about when a vaccine might be available, or how efficacious it might be, saying that a 'sterilizing' vaccine providing full protection against SARS-CoV2 might take longer to develop than one which could provide partial protection.
However Bingham did also highlight how advanced the Oxford team was compared with other groups: "The Oxford study will have likely vaccinated all their efficacy subjects before any of the other vaccines actually start their big efficacy trials. So that just gives you a scale of how far ahead they are versus the other companies."
Kate Bingham
Nevertheless, there are still many unknowns regarding AZD1222, not least the Phase I/II data already generated, which the Oxford team has still not published. This is in clear contrast with most of its competitors, who have presented topline data or published in full in peer-reviewed journals. Other frontrunners who have already shared Phase I/II data include Moderna, Tianjin CanSino Biotechnology Inc. and Sinovac Biotech Ltd.
Pfizer is the latest to share its data, presenting encouraging early results from its mRNA-based collaboration with BioNTech on 1 June. (Also see "Pfizer Unveils Promising Early Data On COVID-19, Sends Moderna Shares Down" - Scrip, 1 Jul, 2020.)
The Oxford team has been confident enough about their timelines to predict that AZD1222 could gain emergency use approvals from regulators as early as September – a forecast date earlier than any of its competitors, though Pfizer says an October authorization for its vaccine is achievable.
Gilbert nevertheless made it clear that predicting timelines for efficacy results from the Phase III trials was very difficult, as this depended on exposure of the vaccinated volunteers to SARS-CoV-2, a factor beyond the control of any of the developers.
Eisai's Eritoran Selected For COVID-19 Trial
Eisai Co. Ltd.'s eritoran, which failed as a treatment for sepsis almost a decade ago, has been selected as the first investigational immune modulation therapy to be included in the subset of the large platform REMAP-COVID study designed to assess various treatments for COVID-19.
The Japanese drugmaker has teamed up with the Global Coalition for Adaptive Research and the University of Pittsburgh Medical Center to test eritoran, a TLR-4 antagonist, alone and in combination with other drugs to evaluate its effectiveness in COVID-19 hospitalized patients. The drug is designed to suppress the over-production and release of various pro-inflammatory mediators, ie, cytokine storm, and Eisai hopes to prove that eritoran can protect against damage in COVID-19 patients’ lungs and other organs.
REMAP-CAP (randomised, embedded, multi-factorial, adaptive platform trial for community-acquired pneumonia), was originally designed to find optimal treatments for severe pneumonia both in non-pandemic and pandemic settings. When COVID-19 began, it rapidly pivoted to pandemic mode and the adaptive design of the REMAP-COVID substudy means it has a number of arms, including antibiotics, hydrocortisones and now immuno-modulatory drugs.
Eritoran was previously observed to be safe in a large Phase III trial for sepsis but the study was terminated in 2011 after the drug failed to prove effective. The compound showed potential as a flu treatment in studies back in 2013 but the asset has not been a priority for Eisai of late. (Also see "Eisai Drug That Failed For Sepsis Could Be New Way To Treat Evolving Flu" - Scrip, 2 May, 2013.)