A malaria vaccine from Oxford University has secured its first approval, from Ghana, which is ramping up efforts to combat the disease that kills a child every minute, and more than 600 000 people a year, most of them children in Africa.
Days later, approval for the R21 jab was granted to Nigeria as well.
It marks the first time, ever, that a major vaccine has been approved in African countries before rich nations, reports Reuters.
The effort is one of several focused on eliminating the disease – the complicated structure and lifecycle of the malaria parasite having long stymied efforts to develop vaccines.
Regulators said the approvals were unusual as they have come before the publication of final-stage trial data for the vaccine.
In a separate Reuters report, Nigeria’s National Agency for Food and Drug Administration and Control (Nafdac) said: “A provisional approval … shall be done in line with the WHO’s Malaria Vaccine Implementation Guideline.”
Nigeria, the continent’s most populous nation, is the world’s worst-affected country with 27% of global malaria cases and 32% of global deaths, according to a 2021 WHO report.
It was unclear when the vaccine might be rolled out in Ghana or Nigeria as other regulatory bodies, including the WHO, are still assessing its safety and effectiveness.
“While granting the approval, the agency has also communicated the need for expansion of the clinical trial conducted to include a phase 4 clinical trial/pharmacovigilance study to be carried out in Nigeria,” Nafdac’s director-general, Mojisola Christianah Adeyeye, said.
Mid-stage data from the R21 trial, published in The Lancet in September and involving more than 400 children, showed vaccine efficacy of between 70% and 80% at 12 months after the fourth dose.
There is also an ongoing phase three clinical trial involving 4 800 children in Burkina Faso, Kenya, Mali and Tanzania.
Last year, the World Health Organisation endorsed the first malaria vaccine, Mosquirix, from British drugmaker GSK, but a lack of funding and commercial potential has thwarted the company's capacity to produce as many doses as needed.
The Oxford vaccine, which has secured regulatory approval in the age group at highest risk of death from malaria – children aged from five months to three-years-old – has a manufacturing advantage, thanks to a deal with Serum Institute of India to produce up to 200m doses annually.
In contrast, GSK has committed to produce up to 15m doses of Mosquirix every year through 2028, well under the roughly 100m doses a year of the four-dose vaccine the WHO says is needed long-term to cover around 25m children.
In the research, vaccine effectiveness was 80% in the group that received a higher dose of the immune-boosting adjuvant component of the vaccine, and 70% in the lower-dose adjuvant group, at 12 months after the fourth dose. The doses were administered before the peak malaria season in Burkina Faso.
Late-stage data, suggesting a similar vaccine performance as in the phase two trial, has been shared with regulatory authorities over the past six months, Oxford scientist Adrian Hill said.
Childhood vaccines in Africa are typically paid for by international organisations such as Gavi and Unicef after they have been backed by the WHO.
This is the first time that a major vaccine has been given the green light first in an African country, before wealthy countries, Hill added, noting that it was unusual that a regulatory authority in Africa had reviewed the data faster than the WHO.
“Particularly since Covid, African regulators have been taking a much more proactive stance, they’ve been saying…we don’t want to be last in the queue.”
Study details
Efficacy and immunogenicity of R21/Matrix-M vaccine against clinical malaria after 2 years' follow-up in children in Burkina Faso: a phase 1/2b randomised controlled trial
Mehreen Datoo, Hamtandi Magloire Natama, Athanase Somé, Duncan Bellamy,
Ousmane Traoré, Toussaint Rouamba, et al.
Published in The Lancet on 7 September 2022
Summary
Background
Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination.
Methods
This double-blind phase 1/2b randomised controlled trial was done in children aged 5–17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 μg R21/25 μg Matrix-M, 5 μg R21/50 μg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety.
Findings
Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 μg R21 adjuvanted with 25 μg Matrix-M, 137 received 5 μg R21 adjuvanted with 50 μg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 μg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ –0·32 [95% CI –0·45 to –0·19]; p=0·0001) and second year of follow-up (–0·20 [–0·34 to –0·06]; p=0·02).
Interpretation
A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations.
Reuters article – Ghana first to approve Oxford's malaria vaccine (Open access)
Reuters article – Nigeria regulator grants approval to Oxford's malaria vaccine (Open access)
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