Candidate: AZD1222 (formerly ChAdOx1 nCoV-19)
Type: Vaccine based on an adenovirus vaccine vector and the COVID-19 spike protein. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.
Status: Researchers from AstraZeneca, the University of Oxford, and partners on July 20 published positive preliminary data from the Phase I/II COV001 trial (NCT04324606) showing AZD1222 to have an acceptable safety profile, and favorable immunogenicity against the virus. Among the 543 participants randomized to AZD1222, a single dose resulted in a four-fold increase in antibodies to the SARS-CoV-2 virus spike protein in 95% of participants at Day 28 after injection, the researchers reported. In all participants, a T-cell response was induced, peaking by day 14, and maintained two months after injection.
Spike-specific T-cell responses among AZD1222 participants peaked on day 14, while anti-spike immunoglobulin G (IgG) responses rose by day 28 and were boosted following a second dose, the researchers reported. Neutralizing antibody responses against SARS-CoV-2 were detected in 32 of 35 participants after a single dose when measured via microneutralisation assay (MNA80) and in all 35 participants when measured via the 50% plaque reduction neutralization assay (PRNT50). After a booster dose, all participants had neutralizing activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg virus neutralization [VN] on day 56). Neutralizing antibody responses correlated strongly with antibody levels measured by ELISA
“The preliminary results of this first-in-human clinical trial supported clinical development progression into ongoing phase 2 and 3 trials,” the researchers concluded in their study, published in The Lancet.
The single-blinded, randomized, multi-center study is designed to determine the efficacy, safety, and immunogenicity of AZD1222 in 1,077 healthy adult volunteers aged 18–55 years across five trial centers in southern England. The trial compared a single dose of AZD1222 against the meningococcal conjugate vaccine MenACWY as a control. Ten participants also received two doses of AZD1222 one month apart. The trial, a collaboration between the Group and the Jenner Institute, started in March and began recruiting patients on April 23, after U.K. Health Secretary Matt Hancock pledged £20 million in government funding to support development of the vaccine.
A week earlier, IQVIA said it will partner with AstraZeneca to accelerate development of AZD1222 by speeding up U.S. clinical studies designed to demonstrate its efficacy–including an “expansive” trial that is expected to begin enrolling participants “this summer.” The partnership will use IQVIA’s Virtual Trial solutions including Study Hub, which can facilitate either all-virtual or hybrid in-person and virtual studies.
IQVIA said the partnership was part of Operation Warp Speed, through which President Donald Trump’s administration has committed the nation to delivering 300 million vaccine doses protecting against SARS-CoV-2 by January 2021.
World Health Organization (WHO) Chief Scientist Soumya Swaminathan, MD, MBBS, told reporters June 26 she considered AZD1222 “probably the leading candidate” among COVID-19 vaccine candidates in development worldwide. WHO counts more than 200 such candidates worldwide, of which 15 are in clinical trials.
AstraZeneca will receive fast-track access to sterile vaccine drug product manufacturing capacity for clinical trial supply of AZD1222 from Symbiosis Pharmaceutical Services, through a supply agreement of undisclosed value announced by Symbiosis on June 22. The agreement with Symbiosis, based in Stirling, Scotland, U.K., is the 10th supply-and-manufacturing deal signed by AstraZeneca for AZD1222.
Sarah Gilbert, PhD, professor of vaccinology at Oxford University, a leader of the effort to develop AZD1222, told the U.K. House of Commons Science and Technology Committee on June 23 that researchers were “very interested in looking at delivery of the vaccine to the respiratory tract, either intranasal delivery or aerosol delivery. In addition to Gilbert, Oxford’s team is led by Professors Andrew Pollard, MBBS, PhD; Teresa Lambe, PhD; Sandy Douglas, DPhil; and Adrian Hill, DPhil. The team started work designing a vaccine in January.
Gilbert was among scientists at Oxford and The Pirbright Institute who published a preprint study in bioRxiv on June 20 reporting that 42 days following the start of dosing, T cell responses were higher in one mouse strain—and especially so in pigs—that received a second “boost” dose of AZD1222 28 days after the initial “prime” dose, compared to receiving only a prime dose. “Further clinical studies are needed to assess immunogenicity after prime-boost vaccination and the impact on clinical efficacy and durability of the immune response,” the researchers cautioned.
Hill, the director of Oxford’s Jenner Institute, told a webinar of the Spanish Society of Rheumatology that the “best scenario” for AZD1222 reaching the market would be in October—one month later than projected June 16 by Cobra Biologics when it said it signed a supply agreement with AstraZeneca to provide GMP manufacture of AZD1222 Oxford-led consortium to rapidly develop, scale-up and produce the vaccine.
Joining Cobra and University of Oxford’s Jenner Institute are cGMP contract manufacturing organizations ADVENT and Halix, Pall Life Sciences, University of Oxford Clinical Biomanufacturing Facility, and the Vaccines Manufacturing and Innovation Centre. Cobra said earlier this year it was planning to facilitate efficient production of a GMP working cell bank, then 200L GMP viral vaccine. Consortium partners said they expected to develop and manufacture the vaccine candidate in multiple batches, to support a 1 million dose scale batch size as soon as the summer.
A day earlier, AstraZeneca further boosted its manufacturing capacity by agreeing to use Catalent’ manufacturing facility in Anagni, Italy, to increase its vial filling and packaging capacity, and prepare for large-scale commercial supply of AZD1222. The value of the agreement, announced June 15, was not disclosed.
AstraZeneca’s manufacturing scale-up of AZD1222 will include Italy as well as other European nations: On June 13, the company said it inked the first agreement signed by the new Inclusive Vaccines Alliance (IVA), which was formed by Italy as well as France, Germany, and the Netherlands to secure COVID-19 vaccine doses as quickly as possible. AstraZeneca has agreed to supply the IVA with up to 400 million doses of AZD1222 to nations within the alliance at no profit, starting by the end of 2020.
AstraZeneca also agreed to use the molecule-to-market contract development and manufacturing (CDMO) services of Emergent BioSciences, through a collaboration disclosed June 11 and valued at $87 million.
Three days earlier, AZD1222 gained additional production capacity when the Vaccines Manufacturing and Innovation Centre (VMIC)—a not-for-profit organization established to provide the UK’s first strategic vaccine development and advanced manufacturing capability—agreed to provide equipment for Oxford Biomedica to rapidly equip two new GMP manufacturing suites within Oxford Biomedica’s new 7,800 m2 (about 84,000-square-foot) Oxbox commercial manufacturing center in Oxford, U.K. The additional capacity will allow the University of Oxford, AstraZeneca, and partners to help meet vaccine demand in the U.K. and Europe starting in the summer, Oxford Biomedica said, adding that the suites could also be used for other viral vector vaccine candidates.
Earlier in June, AstraZeneca said it had come to terms with partners to produce up to 2 billion doses of AZD1222 per year, double the 1 billion dose goal it articulated a month earlier. The pharma and SII (formerly the Serum Institute of India) agreed to produce 1 billion of the doses for low- and middle-income countries, starting with 400 million doses by year’s end. AstraZeneca will also receive a combined $750 million toward manufacturing and distributing 300 million doses by year’s end from two groups: $383 million from CEPI, the Coalition for Epidemic Preparedness, and $367 million from GAVI, The Vaccine Alliance.
The New York Times reported June 3 that AstraZeneca, the University of Oxford, and partners were among developers of five COVID-19 vaccines identified by President Donald Trump’s administration as most likely to produce a vaccine for the virus, citing unnamed “government officials.” According to the report, the five will receive additional government funding, assistance with clinical trials, and financial and logistical support for manufacturing. A formal announcement is expected in coming weeks.
In May, AstraZeneca said it received $1.2 billion from the Biomedical Advanced Research and Development Authority (BARDA) toward development, production, and delivery of AZD1222. The development and production work to be funded by BARDA will begin this fall, AstraZeneca said. It will include a Phase III trial designed to recruit 30,000 participants, as week as another trial to evaluate the vaccine in children. The trial is set to start in June and run to the end of August, AstraZeneca CEO Pascal Soriot told Bloomberg News.
On the production end, AstraZeneca has concluded its first manufacturing agreements to produce at least 400 million doses of the vaccine, as well as gain total manufacturing capacity for 1 billion doses so far.
AstraZeneca agreed to furnish BARDA with 300 million doses, the U.S. Department of Health and Human Services (HHS) said—four days after the U.K. government secured the other 100 million doses by agreeing to pay AstraZeneca £65.5 million ($80 million).
AstraZeneca said the U.K. will receive the first 30 million doses of AZD1222 in September. The U.S. set to receive the vaccine in October, according to HHS’ announcement.
AstraZeneca said April 30 it will oversee global development, manufacturing, and distribution of the COVID-19 vaccine candidate created by researchers at University of Oxford, and now under study in a human clinical trial. AstraZeneca, the University, and its spinout company Vaccitech—which has joint rights to the platform technology behind the vaccine candidate—said they will start work immediately while hammering out final terms of their collaboration agreement. The partnership is designed to enable rapid production and distribution of the vaccine should it prove effective in clinical studies.
AstraZeneca, the University, and its spinout company Vaccitech—which has joint rights to the platform technology behind the vaccine candidate—said they will start work immediately while hammering out final terms of their collaboration agreement. The partnership is designed to enable rapid production and distribution of the vaccine should it prove effective in clinical studies.
The Jenner Institute and MilliporeSigma said April 14 they had begun preparations for the large-scale production of the former ChAdOx1 nCoV-19, building on a partnership to develop more robust and scalable vaccine manufacturing processes launched in April 2018. Joining the partners April 15 was HALIX, which will apply its viral vector bioprocessing expertise to support the manufacture of Oxford vaccine clinical trial material by transferring an industrial scale drug substance process to its new GMP facilities with capacity up to 1,000 L SUB scale, from a Pall facility in the U.K.
On March 23, Oxford Prof. Sarah Gilbert was awarded £2.2 million ($2.7 million) by the U.K. government toward the research, one of six COVID-19 research projects to receive a combined £20 million ($24.5 million).
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: