In March 2024 Pfizer announced that the European Commission (EC) has granted marketing authorisation for the company’s 20-valent pneumococcal conjugate vaccine, which is marketed in the EU as PREVENAR 20, for active immunisation for the prevention of invasive disease, pneumonia, and acute otitis media caused by Streptococcus pneumoniae in infants, children, and adolescents between the ages of 6 weeks and 18 years.
The authorisation is valid in the 27 EU Member States along with Iceland, Lichtenstein, and Norway. This announcement comes shortly after a positive opinion from the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) and is almost a year after the approval of PREVENAR 20 for children and infants by the US FDA in April 2023. Further approvals have been granted in countries such as Canada, Australia, and Brazil.
PREVENAR 20
PREVENAR 20 includes 13 serotypes from PREVENAR 13 with seven new serotypes, all of which are “global causes of invasive pneumococcal disease” (IPD). They are associated with “high case-fatality rates, antibiotic resistance, and/or meningitis”. The 20 serotypes contained within the vaccine are responsible for “the majority” of currently circulating pneumococcal disease both in the EU and globally.
Pfizer states that the EC authorisation has been informed by evidence from the Phase III clinical trial programme that comprises four core paediatric studies, which collectively enrolled more than 4,700 infants and 800 toddlers and children of all ages.
A significant opportunity
Alexandre de Germay is Pfizer’s Chief International Commercial Officer and Executive Vice President and described the authorisation as a “significant opportunity to improve public health”.
“PREVENAR 20 builds on Pfizer’s decades-long commitment to develop vaccines to help prevent potentially life-threatening infections, and we are proud to now provide the broadest serotype coverage of any pneumococcal conjugate vaccine for children in Europe.”
In February 2024 Pfizer announced top-line ABRYSVO vaccine efficacy and safety data from the ongoing Phase III RENOIR (RSV vaccine Efficacy study iN Older adults Immunised against RSV disease). The trial investigates ABRYSVO in adults aged 60 and above. ABRYSVO is a bivalent vaccine designed to provide broad protection against all RSV-LRTD, “regardless of the virus subgroup”. The basis is the RSV fusion protein (F) in the prefusion conformation, a major target of virus infection blocking antibodies.
Vaccine efficacy
Vaccine efficacy against RSV-associated lower respiratory tract disease (LRTD), which is defined by three or more symptoms, after disease surveillance in season two was 77.8%. Vaccine efficacy after season one was 88.9%, demonstrating “durable efficacy” after two seasons. Furthermore, “consistent” efficacy was demonstrated for both RSV A and RSV B after season two; vaccine efficacy against each subtype was ≥ 80% for LRTD with three or more symptoms.
Vaccine efficacy was also sustained against less severe LRTD, defined by two or more symptoms, from 65.1% after season one to 55.7% after the end of season two. For RSV-associated LRTD vaccine efficacy across both seasons was 81.5%. No new adverse events were reported through the second RSV season beyond reports from the first season.
Dr Annaliesa Anderson, Senior Vice President and Chief Scientific Officer, Vaccine Research and Development, Pfizer, is “encouraged by the level of protection” observed after “two full RSV seasons”.
“These new data indicate that broad and durable protection against both types of RSV that cause disease, RSV A and RSV B, is the potential benefit to having a bivalent vaccine.”
In February the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) announced the approval of a change to the licence of the Comirnaty COVID-19 vaccine to enable thawing and re-labelling outside the NHS. Additionally, approval has been granted for Nuvaxovid COVID-19 to target Omicron XBB 1.5 subvariant. The vaccines have met the regulator’s standards of safety, quality, and effectiveness.
Pfizer/BioNTech’s Comirnaty
MHRA announced that it has approved a change to the license to enable “thawing and re-labelling” of the vaccine by a manufacturer that is outside the NHS. This has been authorised by the MHRA and “confirmed to meet” globally recognised Good Manufacturing Practice standards. The vaccine requires ultra-low storage temperatures of –80 ºC before being thawed for use. Until now, this thawing and distribution has been centrally managed by the NHS.
Novavax’s Nuvaxovid
MHRA also announced the approval of an adapted Novavax COVID-19 targeting the Omicron XBB 1.5 subvariant. It has been approved for use in individuals aged 12 and above. This authorisation was approved through the European Commission (EC) Decision Reliance Route, which links the application to the decision made by the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP).
“In such cases, the MHRA considers the application together with due consideration of the EC decision, before making an independent decision on the quality, safety, and effectiveness of the vaccine.”
Novavax’s President and Chief Executive Officer, John C. Jacobs, commented that the authorisation is “recognition of the role” that his team’s vaccine can have in “protecting the British public against COVID-19 this year”.
“We are in ongoing conversations with additional UK partners to identify potential opportunities to offer our protein-based non-mRNA COVID-19 vaccine to all eligible individuals who want one. We believe this is critical to supporting long-term, broad uptake of a seasonal COVID-19 vaccine in the UK.”
How might the latest approvals support vaccine strategies?
We’re looking forward to opportunities to hear more on COVID-19 vaccine development and improvement at the Congress in Washington this April, with representatives from the companies mentioned here (Pfizer, BioNTech, and Novavax) in attendance. Do join us there by getting your tickets at this link or subscribe for our weekly newsletters for insights and updates.
The World Vaccine Congress in Barcelona is so close (less than a week now!) and we are delighted that our speaker interviews are gearing up in preparation. Today we are excited to share a conversation with Bill Falstich, who will be joining us next week for two sessions. This was a written interview, conducted over email, and we hope you enjoy hearing from him!
Introducing Bill Falstich
As Pfizer’s vice President of Global Supply Chain, Bill is busy leading a team that manages supply for “some of the world’s largest vaccines, a broad Internal Medicines portfolio, and Pfizer’s Paxlovid antiviral.”
“We drive continuous improvement across Pfizer’s Primary Care supply in support of Pfizer’s purpose – delivering breakthroughs that change patients’ lives.”
This includes “aspects of supply chain management such as product strategy and orchestration, product launch management, supply network design, and supply issue resolution”. Bill and his team are “excited” to be “regularly expanding products” to their existing portfolio.
“Thanks to Pfizer’s healthy pipeline of new products there are many launches underway as well as planned, including our most recent successful launch of Pfizer’s RSV vaccine!”
Lessons from the pandemic
Bill’s first session at the Congress investigates “lessons” from Pfizer’s supply chain “overhaul” during the pandemic. We know that flexibility and resilience were key goals for the team, so we asked about how these were achieved. Bill suggests that when the pandemic began, the challenge for Pfizer and partner BioNTech “wasn’t just developing a vaccine” but making it, “by the billions”. He suggests that “it all started with our talented colleagues”.
“When other industries locked down because of the pandemic, our colleagues continued to come on site every day to manufacture critical medicines and vaccines.”
Pfizer’s “wonderful culture” predated the pandemic, says Bill, and this was “reinforced” with what they called “Lightspeed principles” to enable quick and efficient decision making. However, “supply chains are so much more than a single company”.
“We partnered with more than 300 diverse suppliers and contract manufacturers and added dozens of small businesses to our network, helping us boost reliability.”
Resilience was also “strengthened” through the implementation of two “parallel supply chains” in the US and Europe to “ensure that we could provide our vaccine to patients as quickly as possible”. “Appropriate redundancies and flexibility” within the supply chain included extra inventory, increased workers, and multiple suppliers.
“Our diverse ecosystem of suppliers and partners was able to tackle unprecedented challenges, handle any sudden shortfalls, and even produce new products.”
Underpinning all of this in Bill’s eyes, were “digital solutions”. Three technological areas came into focus to drive innovation forward, combining “product technology”, how that technology is manufactured, and the digital technology to support that.
“We brought together a community of people and strategic partners across these three platforms. By utilising these developments to our supply chain, as of September 2023, we have shipped more than 4.7 billion doses to 181 countries and territories in every region of the world.”
Speed meets safety under pressure
During the pandemic there was a demand for speed and precise timing; how did Pfizer tackle these challenges without sacrificing the safety of its processes? Bill states that “Pfizer already knew mRNA could be the key to a different future for vaccines”.
“When the pandemic took hold, Pfizer Global Supply colleagues went from ‘testing’ mode to ‘execution’ mode. However, the ways we worked in the past would not be fast enough.”
Thus, the team ordered prefabricated modules for installation in the Kalamazoo, Michigan site “within just months” instead of building new formulation sites. They managed to build these units in Texas and ship them overnight, installing around 13,000 square feet of modular rooms and “cutting our expansion time in half”. They also worked with technological leaders to “produce critical mechanical components to manufacture the vaccine at speed”, and shipping experts to “execute the distribution of the vaccine flawlessly”.
“We leveraged predictive reliability monitoring, a cutting-edge technology that enabled us to monitor critical pieces of equipment to detect potential fault conditions and generate maintenance work orders before equipment failure, which helped us reduce downtime and increase productivity.”
This enabled the team to “identify issues” as the product was taken to ultra-cold temperatures. Furthermore, they “leveraged sensor technology on the lines”, standardising real-time performance feedback. This meant that batch end times were predictable, reducing manual operator entry, and “saving valuable time”.
“At the core of our ability to scale of production was our people. Rallying around the idea of a ‘lightspeed culture’, we discovered that a unifying belief that we could succeed, and a common goal, allowed us to achieve production in record time.”
Not only were production and supply chain updated, but day-to-day operations were changed, processes streamlined, and silos deconstructed.
Taking mRNA beyond the pandemic
Some of us might think of mRNA vaccines as a pandemic one-hit-wonder, but the technology was ready to go thanks to decades of research, and the story is not over yet. Bill’s panel explores the “post-pandemic path” of mRNA vaccines, so we asked what we can expect from supply chains as we try to leave the pandemic in the past, and how we can better prepare for a future crisis.
“For one, expect more mRNA vaccines in the future.”
Bill tells us that “Pfizer has already launched clinical trials of mRNA influenza vaccines” and is working with BioNTech to “co-develop the first ever mRNA-based vaccine for shingles”.
“We will see technological advancements across supply chains to address the growing global demand for vaccines.”
The example that Bill gives is “high-visibility supply trackers”, which allow for a “deeper understanding of current production levels” and “increase our flexibility in prioritising in-demand products”. GPS tracking that operates 24/7 “can help us respond to supply issues in real-time”, including replacing damaged products immediately.
“This helps us achieve a 99% success rate for delivering our vaccine shipments.”
“As the pandemic forced us to work on a global scale, we also deepened our relationships with ministries of health, trade organisations, and customs agencies.”
These “fortified relationships” enabled “lightspeed” distribution of the authorised COVID-19 oral treatment.
“I anticipate continued close working relationships in this space to ensure the best outcomes for patients all over the world. We must continue to collaborate across the public and private sectors, industries, and areas of expertise.”
However, the responsibility doesn’t just lie with pharma. Bill recommends that governments and international organisations “must incentivise private industry to take on risk for the good of all”. This could be through advance purchase agreements or capacity reservation agreements for medicines and vaccines.
“As it relates to regionalised manufacturing, we must consider how to build ecosystems that enable success – including consistent production volumes, harmonised regulatory approaches, technically strong workforces, and the like.”
Why WVC?
As always, we conclude by inviting our speakers to share their reasons for joining us at the event. Bill looks forward to the “new connections” and chance to “learn from others” at the Congress.
“We are so fortunate to work in such a dynamic and fast-growing space, and I am excited to have the opportunity to hear other speakers share their insights and expertise.”
We hope that the Congress will be as fruitful for Bill as it undoubtedly will be for those of us who hear more from him. Thank you to Bill and his team for facilitating this conversation and providing such valuable insights. If you enjoyed this interview, why not subscribe to our newsletters so you don’t miss more like this? If you haven’t yet got your ticket to join us at the event next week, make sure you do that now.
In August 2023 Pfizer announced that the US FDA has approved its vaccine against RSV in infants through immunisation of pregnant individuals. ABRYSVO is a bivalent RSV prefusion F (RSVpreF) vaccine aimed at the prevention of lower respiratory tract disease (LRTD) and severe LRTD caused by RSV in infants from birth up to six months of age. It is approved for use in pregnant individuals from 32-36 weeks gestational age.
ABRYSVO
The vaccine is unadjuvanted and comprises two preF proteins that have been selected to optimise protection against RSV A and B strains. It has been demonstrated “safe and effective”. It is a vaccine indicated for:
The prevention of LRTD caused by RSV in people aged 60 and older
Pregnant individuals at 32 through 36 weeks gestational age for the prevention of LRTD and severe LRTD caused by RSV in infants from birth to 6 months old
In March 2022, Pfizer was granted Breakthrough Therapy Designation by the FDA for ABRYSVO, followed by the FDA’s acceptance of a Biologics License Application under priority review for infants in February 2023. The recent decision by the FDA is based on data from a pivotal Phase III clinical trial called MATISSE (MATernal Immunisation Study for Safety and Efficacy). This was a randomised, double-blinded, placebo-controlled study with results published in The New England Journal of Medicine.
Two further clinical trials have been initiated to evaluate ABRYSVO. One is being conducted in children at higher risk for RSV disease between the ages of 2 and 18. A second is evaluating adults between the ages of 18 and 60 who are at higher risk for RSV due to underlying medical conditions, and adults aged 18 and older who are immunocompromised and at high-risk for RSV. Post-marketing studies and surveillance programmes are also planned to further describe the safety of the vaccine.
A significant milestone
Dr Annaliesa Anderson, Pfizer’s Senior Vice President and Chief Scientific Officer, Vaccine Research and Development, described the approval as a “significant milestone for the scientific community and for public health”, as it is the “first and only maternal immunisation” to protect infants from RSV. She is grateful to the participants of the clinical trial and study investigator teams, as well as colleagues at Pfizer, for their “commitment to making this vaccine available”.
“Today a long-sought-after goal to deliver a maternal vaccine will help protect infants six months of age or younger – when they are at greatest risk of possible serious consequences from RSV – has been achieved.”
Dr Eric A.F. Simões, Clinical Professor, Paediatrics-Infectious Diseases, University of Colorado School of Medicine and Children’s Hospital Colorado, Aurora, commented that the approval is a “major triumph”.
“Newborns and young infants – whose immune systems are still developing and are not yet strong enough to defend against infections – may now be protected from RSV from the moment of birth through maternal immunisation.”
In July 2023 Pfizer announced data from a Phase II study investigating its hexavalent capsular polysaccharide (CPS) conjugate Group B Streptococcus (GBS) vaccine candidate, GBS6. This is being developed for maternal administration to protect infants against invasive GBS disease. Results, published in The New England Journal of Medicine (NEJM) will inform a planned Phase III clinical development programme. They show that GBS6 generated “robust” maternal antibody responses against the 6 GBS CPS serotypes in the vaccine. These antibodies were “efficiently” transferred to infants at ratios of ~0.4-1.3 depending on GBS6 group.
GBS
The study states that GBS is a “common cause” of sepsis and meningitis in newborns up to 89 days old, with the primary risk factor being exposure to maternal rectovaginal group B streptococcal colonisation during delivery. Additionally, ascending group B streptococcal infection in the mother can affect the foetus before delivery, causing intraamniotic infection, premature labour, or stillbirth. In many high-income countries, pregnancy screening is available, with intrapartum antibiotic prophylaxis more than 80% effective in the prevention of early-onset disease in infants (0 to 6 days of age). However, it is not as effective against late-onset disease (from 7 to 89 days) or prebirth sequelae associated with infection.
The authors claim that a maternal vaccine, administered during pregnancy, could potentially prevent both early and late-onset disease and “may mitigate the need for intrapartum antibiotic prophylaxis” for “otherwise healthy women”.
“Such a vaccine could be beneficial because intrapartum antibiotic prophylaxis may contribute to antimicrobial resistance and disrupt development of the infant microbiome.”
Furthermore, it would be a “much-needed measure” against GBS infection for the “substantial percentage of pregnant women living in resource-limited community settings”.
GBS6
The vaccine is a hexavalent anti CPS/genetically detoxified diphtheria toxin cross reactive material (CRM) 197 glycoconjugate, developed to help prevent invasive GBS in newborns. Previously, Pfizer has successfully used polysaccharides conjugated to CRM in pneumococcal vaccines. GBS6 is designed to offer protection against the 6 “most prominent” serotypes, which collectively account for 98% of GBS disease worldwide.
In trial
The Phase II trial was divided into 3 stages:
Evaluated safety and immunogenicity in 66 healthy, nonpregnant individuals in South Africa.
The focus of the publication – evaluated safety and immunogenicity in 360 healthy pregnant individuals aged 18 to 40 years and their infants in South Africa.
Evaluation of a final formulation in 216 healthy pregnant individuals and their infants in South Africa, the US, and UK.
The safety profile for mothers and infants was similar between the vaccine and placebo groups. Dr Annaliesa Anderson, SVP and CSO, Vaccine Research and Development, Pfizer, identifies “hope” in the recent findings.
“Group B Streptococcus can cause potentially devastating diseases in infants, including sepsis, pneumonia, and meningitis. Annually, there are nearly 400,000 cases of infant disease and approximately 138,000 stillbirths and infant deaths worldwide due to GBS.”
Dr Anderson hopes to prevent these cases and deaths with a “successfully developed and approved” vaccine.
“Building on decades of expertise and knowledge in vaccines, we are committed to helping protect newborns and young infants through maternal immunisation.”
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In February 2023, a few days after the FDA requested further studies into the link between GBS and its RSV vaccine candidate, Pfizer announced that the FDA had voted that available data supports the “safety and effectiveness” of the vaccine. The Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 7 to 4 on safety and 7 to 4 on effectiveness.
What does the vote mean?
Although the VRBPAC provides recommendations to the FDA, Pfizer emphasises that they “are not binding” and the FDA is still considering the approval of RSVpreF with a decision expected in May 2023.
The vote was based on available evidence from Pfizer, including data from the RENOIR study last year. However, some of the members of the committee expressed concerns about the safety of the candidate, particularly in light of the perceived connection between the vaccine and GBS. Dr Hana El Sahly, Committee Chair, described the risk as “concerning”, voting in favour of the vaccine based on efficacy but against its safety profile.
A step forward for Pfizer with GSK following
Dr Annaliesa Anderson, Senior Vice President and Chief Scientific Officer, Vaccine Research and Development at Pfizer, described the “significant need” to protect older adults from “serious illness, hospitalisation, or even death” from RSV.
“We are encouraged by the outcome of today’s VRBPAC meeting as it is a testament to the strength of our science and dedication to bringing this important vaccine candidate to the market.”
Dr Anderson looks forward to “working with the FDA” to complete the application.
Closely following Pfizer in the ‘race’ to secure approval for its RSV vaccine is GSK. The Committee meets again today, on the 1st March, to evaluate its candidate following “positive” results last year.
For more updates on RSV vaccine developments and the timeline to success, join us for discussions with representatives of these key participants in the efforts to achieve it at the World Vaccine Congress in Washington this April.
Following the FDA’s acceptance for review of a Biologics License Application for Pfizer’s respiratory syncytial virus (RSV) vaccine candidate, the agency has asked for further studies into the connection between the vaccine and cases of Guillain-Barré syndrome (GBS). Documents released in February 2023 indicate that if the vaccine is approved, “post-marketing surveillance” will be warranted.
GBS and the vaccine
Guillain-Barré syndrome (GBS) sometimes occurs when the immune system affects the peripheral nervous system, often after an infection. It is most commonly observed in the hands or feet, before spreading to other parts of the body, with symptoms such as numbness, muscle weakness, or pain.
The FDA reports than one case of GBS was identified 7 days after vaccination, with a case of Miller Fisher syndrome, “considered a variant of GBS”, identified 8 days after vaccination. Thus, a total of 2 cases among 19,942 vaccinated participants were recorded. The FDA puts this into the context of a background rate of 1.5-3 cases per 100,000 people each year among US adults. Consequently, it is requesting that GBS and other “immune-mediated demyelinating conditions” are included in the Pharmacovigilance Plan (PVP).
Furthermore, the FDA requests that Pfizer proposes a post-marketing safety study to assess the risk of GBS and other conditions among vaccine recipients post-licensure. Pfizer stated that it will do this.
The race continues
Despite this hurdle, Pfizer continues to keep pace in the race for an RSV vaccine with competitors such as GSK and Moderna also developing candidates. CNN reports that GSK also reported a ‘potential case” of GBS among vaccine recipients but found “insufficient evidence” for confirmation of a diagnosis.
Data for both GSK and Pfizer candidates is under consideration by the CDC, with “post licensure surveillance” being described as “critical” by the Advisory Committee on Immunisation Practices.
For more updates on RSV from key players in the vaccine industry, join us at the World Vaccine Congress in Washington this April.
In February 2023 Pfizer and Valneva announced that Pfizer, study sponsor of the VALOR Phase III clinical study, has decided to “discontinue a significant percentage of participants in the US” who had been enrolled already.
This discontinuation represents “approximately half of the total recruited participants” and is due to “violations of Good Clinical Practice (GCP) at “certain clinical trial sites”. The statement from Pfizer and Valneva emphasises that these were run by a “third-party clinical trial site operator”. Furthermore, the discontinuation was not caused by safety concerns associated with the vaccine candidate.
GCP and violations
GCP is internationally recognised as a set of requirements to uphold ethical and scientific quality in clinical trials. Valneva states that they put “participants’ interests first and ensure high scientific integrity”.
Pfizer learnt of “potential violations” and responded with a “thorough review” of both operations and data collections, following “standard operating safeguards” to determine the “correct course of action”.
Consequences for the trial
The joint statement suggests that the wider trial is ongoing with other sites that are not managed by the third party responsible for these violations and continues to enrol new participants. Participants are being notified, and Pfizer has also notified the appropriate regulatory agencies and the independent Institutional Review Board for the study.
“Integrity of data collected in clinical trials is critical to provide evidence and confidence in a potential vaccine or medicine’s safety and efficacy.”
Pfizer and Valneva are “committed to collecting robust data” in order to achieve regulatory submission of VLA15, the candidate in investigation. As we have previously explored, strong immunogenicity data were reported from Phase II studies.
We will hear more from representatives of Pfizer and Valneva at the Congress in Washington this April, as well as specific sessions on improving clinical trial procedures and outcomes.
On 1st December 2022 Pfizer and Valneva reported antibody persistence data 6 months after the completion of a vaccination schedule with their Lyme disease vaccine candidate, VLA15. This was reported in both children and adults, the first time that antibody resistance data are reported in paediatric populations for this vaccine candidate.
Moving through the Phases
As we reported earlier this year, Phase II in April 2022 produced “positive immunogenicity and safety data”. As a result, the investigations continued, to evaluate the persistence of antibodies 6 months after the study of a Month 0-2-6 and Month 0-6 vaccination schedule. This was done in healthy adults and paediatric participants.
Data were collected in 96 health adults and 81 paediatric participants (5-17 years of age) for the schedule involving vaccination at months 0-2-6, and 84 healthy adults and 78 paediatric patients for the month 0-6 schedule.
Although antibodies did decline over time, they remained “above baseline”, confirming persistence 6 months after the completion of both schedules. Antibody levels generally remained higher after the 3-dose schedule, compared to the 2-dose schedule. The statement also indicated that “no vaccine-related serious adverse events (SAEs) and no safety concerns” were observed in the follow up.
Several months ago, Pfizer and Valneva initiated a Phase III study, VALOR. Enrolment is taking place across Europe and the US, with up to 6,000 participants over the age of 5 expected to receive 3 doses of VLA15 or a saline placebo, followed by a booster dose.
Validation of the vaccine
Dr Juan Carlos Jaramillo, CMO at Valneva, is “pleased with these antibody persistence data”. They “further validate” the 3-dose vaccination strategy for the Phase III study and the “acceptable safety and tolerability profiles of our vaccine candidate”.
“Lyme disease continues to spread, representing a high unmet medical need that impacts the lives of many in the Northern Hemisphere, and each new report of positive data takes us a step closer to potentially bringing this vaccine to both adults and children who could benefit from it.”
Dr Annaliesa Anderson, SVP and CSO of Vaccine Research and Development at Pfizer agreed, suggesting that “rates of Lyme disease continue to increase globally”.
“These six-month antibody persistence data are encouraging, and we hope that the data generated from the Phase III studies will further support the positive evidence for VLA15 to date.”
To hear from speakers from both Pfizer and Valneva at the World Vaccine Congress in Washington 2023 get your tickets now.
Pfizer announced in September 2022 that the first participants in its “pivotal” Phase III influenza trial had been dosed. The trial will investigate the “efficacy, safety, tolerability, and immunogenicity” of the quadrivalent modified RNA (modRNA) vaccine. It will involve around 25,000 health adults.
The flu programme
The vaccine candidate encodes WHO’s “recommended strains for the Northern Hemisphere 2022/3 cell culture – or recombinant-based influenza vaccines”. Pfizer reports that the study is “informed by previously shared data” from the ongoing Phase II trial. The evidence of safety and an immunogenicity profile supports the advancement of this programme. Pfizer’s broader influenza vaccine programme is focused on “leveraging mRNA technology in a vaccine to help protect against the flu”. Apart from this modRNA candidate, other studies are exploring “more novel mRNA technology” such as self-amplifying RNA (saRNA).
Pfizer entered an agreement with BioNTech in 2018 that enabled Pfizer to “carry out the clinical development and commercialisation of mRNA-based influenza vaccines”. It reports that, dependent on approval and commercialisation, BioNTech will receive a royalty on sales.
A long winter ahead
This announcement comes amidst fears that this year’s flu season will be particularly damaging. Aside from worrying predictions, influenza already causes between 12,000 and 52,000 deaths in the US. Additionally, $25 billion is wasted as “economic loss”. Pfizer suggests that every year vaccines, matched to circulating influenza strains, only offer between 40% and 60% protection. As strains continue to change, identifying and producing the appropriate strain is “difficult”. However, with the flexibility of mRNA technology and its “rapid manufacturing” Pfizer hopes to promote “better strain matches” and faster, large-scale manufacturing of vaccines. Dr Annaliesa Anderson of Pfizer identified the need to “better address the burden of influenza”.
“Our experience with RNA viruses and mRNA technology has given us an even deeper understanding of the opportunity to potentially provide more efficacious vaccines that could further reduce the yearly rates of the sever outcomes of viral disease like flu, including hospitalisation and death.”
She is “excited” at the prospect of this trial and hopes it will deliver an “improved” vaccine to tackle the “significant burden” of the disease. To support in the global effort, Pfizer emphasised its “public commitment to help reduce health disparities through its clinical trials”. Thus, it is expected that this trial will include “racial and ethnic diversity” as is reflective of the country of investigation.
Read more about the potential for a universal flu jab here or come to the World Vaccine Congress to learn more about preparing for flu season.
Pfizer announced in September 2022 that its investigational Group B Streptococcus (GBS) vaccine candidate, GBS6, or PF-06760805, had received Breakthrough Therapy Designation from the FDA. The vaccine is intended for the “prevention of invasive GBS disease…by active immunisation of their mothers during pregnancy”.
The decision comes amidst an ongoing study, evaluating the safety and immunogenicity of GBS6 in healthy pregnant women between the ages of 18 and 40, who received vaccination during their second or early third trimesters. This is a placebo-controlled Phase II study, NCT03765073.
What is GBS?
GBS is a bacterium that causes “potentially devastating diseases in infants”, such as sepsis, pneumonia, and meningitis during the first 3 months of life. Pfizer stated that “about 1 in 4 pregnant women carry GBS bacteria in their body” with the potential to pass it on to their infant “during or prior to birth”. The annual global burden is an estimated 410,000 cases worldwide, with more than 147,000 stillbirths and infant deaths.
Breakthrough Therapy Designation
The FDA’s Breakthrough Therapy Designation is “designed to expedite the development and review” of vaccines that are considered better than current therapies. In order to obtain this status, preliminary clinical evidence must demonstrate “substantial improvement” on “clinically significant endpoints”. The attainment of this status follows the FDA’s decision to grant Fast Track status to GBS6 in March 2017.
GBS6
The vaccine candidate is designed to offer protection against the “6 most prominent GBS serotypes”, which comprise 98% of the disease. The vaccine is an investigational maternal vaccine, hexavalent anti capsular polysaccharide (CPS)/cross reactive material 197 glycoconjugate.
It is undergoing evaluation in a Phase II study across South Africa, the UK, and the US. In April 2022 GBS6 was granted PRIME designation by the EMA’s Committee for Medicinal Products for Human Use (CHMP). This “provides enhanced support for the development of medicines that target an unmet clinical need”. In 2016 Pfizer reported receiving a grant from the Bill and Melinda Gates Foundation towards the ongoing clinical trial and a “parallel non-interventional natural history study”.
Dr Annaliesa Anderson, Senior Vice President and Head of Vaccine Research and Development at Pfizer, stated that GBS infections have “devastating” effects on new-borns and their families. Although she credits prenatal screening and antibiotics during childbirth with providing protection against GBS, she is concerned that this approach is not “fully protective in the first week of life”. Furthermore, it “presents multiple challenges in low- and middle-income countries” and “has not been shown effective” up to the first 3 months of life.
“If approved for pregnant women, GBS6 could help protect new-borns from the serious illnesses caused by this disease like meningitis, pneumonia, and sepsis”.
Dr Anderson is “encouraged” by the FDA’s decision and is prepared to discuss the vaccine candidate with the FDA and other agencies to “potentially reduce neonatal deaths” as well as the “global disease burden of GBS”.
To hear from speakers from Pfizer at the World Vaccine Congress in Europe 2022 get your tickets here.
Following Moderna’s announcement that it would be filing patent infringement lawsuits against Pfizer and BioNTech, the two companies have responded. In a press release BioNTech acknowledged the accusations, resolving to “vigorously defend against all allegations”. Pfizer also responded in a statement to Science, suggesting surprise at Moderna’s move.
BioNTech emphasised that the work behind the Comirnaty vaccine is “original”. The statement, issued on 26th August 2022, suggested that the company “values and respects” intellectual property rights but “remains confident in its intellectual property”.
“It is an unfortunate but rather regular occurrence that other companies make allegations that a successful product potentially infringes their intellectual property rights”.
Although the company declined to comment on any legal strategy, it is clear that the stance is defensive.
Further acknowledgement of the legal action came from Pfizer, who, as of 29th August had “not yet fully reviewed the complaint”. It suggested to Science that it was “surprised by the litigation”. Echoing BioNTech’s approach the spokesperson emphasised that they are “confident in [their] intellectual property”.
Kevin Noonan, a biotechnology patent attorney from Chicago, described the suit as “David versus Goliath”, with Moderna assuming the role of David. He suggested that this enforcement of prior patents would open Moderna up to future attacks. Georgetown University’s Lawrence Gostin expects Pfizer to be careful with their response, anticipating future invalidation of patents: “they’re going to have to walk a tightrope”. However, this lawsuit indicates a much deeper issue for global health. He is concerned that mRNA technology will become “more monopolistic” whereas we want “as many innovators” at the table as possible.
For more from representatives of Moderna, Pfizer, and BioNTech at the World Vaccine Congress in Europe get your tickets here.
Moderna announced in August 2022 that it is filing patent infringement lawsuits against Pfizer and BioNTech. In a statement released on 26th August, Moderna suggested that the Covid-19 vaccine Comirnaty “infringes patents Moderna filed between 2010 and 2016″. These cover Moderna’s “foundational mRNA technology”. This technology, “critical to the development” of Moderna’s Spikevax Covid-19 vaccine, is said to have been copied “without Moderna’s permission, to make Comirnaty”.
Moderna’s CEO Stephane Bancel said that these lawsuits would “protect” the technology platform that Moderna “pioneered”. He reflected that “billions of dollars” had been invested in the decade before the pandemic.
“This foundational platform, which we began building in 2010, along with our patented work on coronaviruses in 2015 and 2016, enabled us to produce a safe and highly effective Covid-19 vaccine in record time”.
Bancel stated that this mRNA technology platform was critical to further development into medicines against “infectious disease” as well as “autoimmune and cardiovascular diseases and rare forms of cancer”.
Copycat vax
Moderna’s statement suggests that Pfizer and BioNTech “copied two key features” of patented technologies. These, it emphasises, are “critical to the success of mRNA vaccines”. Moderna insists that neither company had sufficient experience in mRNA vaccines, and therefore “knowingly followed Moderna’s lead”. Although Pfizer and BioNTech took several vaccine candidates to testing, they moved forward with a vaccine that “has the same exact mRNA chemical modification to its vaccine as Spikevax”. Moderna says that its scientists began to develop this in 2010 and validated it in human trials in 2015.
Moderna goes on to accuse Pfizer and BioNTech of copying the “approach to encode for the full-length spike protein in a lipid nanoparticle formulation for a coronavirus”. It traces its claim to this approach when scientists created a coronavirus vaccine against MERS, years ago.
Expectations and exceptions
In October 2020 Moderna pledged not to “enforce its Covid-19 related patents” in order to align with a “commitment to equitable global access”. However, this pledge was “updated” in March 2022 when, according to Moderna, “vaccine supply was no longer a barrier to access in many parts of the world”. This update made exceptions for “any Covid-19 vaccine used in the 92 low- and middle-income countries in the Gavi COVAX Advance Market Commitment (AMC 92)” but “expected” other companies to “respect its intellectual property rights”. Pfizer and BioNTech “failed to do so”, insist Moderna.
Chief Legal Office Shannon Thyme Klinger believes that Pfizer and BioNTech “unlawfully copied Moderna’s inventions” and have gone on to use them without requesting permission. Therefore, Moderna “expects Pfizer and BioNTech to compensate Moderna for Comirnaty’s ongoing use” of the technology.
“Our mission to create a new generation of transformative medicines for patients by delivering on the promise of mRNA science cannot be achieved without a patent system that rewards and protects innovation.”
Moderna will not seek to remove Comirnaty from the market or an injunction to prevent future sale. Furthermore, it is “not seeking damages” related to sales to AMC 92 countries or sales where the US Government would be responsible. It is also not seeking damages for “activities occurring before March 8, 2022”.
To hear from representatives from Moderna, Pfizer, and BioNTech at the World Vaccine Congress in Europe get your tickets here.
Pfizer announced in August 2022 that the Phase III clinical trial of RENOIR had demonstrated “positive top-line data”. RENOIR (RSV vaccine Efficacy iN Older adults Immunised against RSV disease) investigates Pfizer’s bivalent RSV prefusion F vaccine candidate, RSVpreF. This study looked into the administration of the candidate to adults over the age of 60.
RSV
RSV disease is “characterised by several respiratory symptoms” and can be particularly dangerous for infants and older adults. Pfizer reported that an estimated “336,000 older adults are hospitalised globally due to RSV”. Furthermore, in the US, RSV infections in older adults “account for approximately 177,000 hospitalisations” with up to 14,000 deaths each year. There are currently “no prophylactic or therapeutic options” for older adults.
RSVpreF
The bivalent vaccine candidate comprises two preF proteins, selected to “optimise protection against RSV A and B strains”. It builds on “foundational basic science discoveries”. Among these is the detailed crystal structure of prefusion F, produced by the NIH. Prefusion F is a “key form of the viral fusion protein (F) that RSV uses to enter human cells”. Pfizer credits NIH research for demonstrating that “antibodies specific to the prefusion form” are “highly effective at blocking virus infection”. Following this, Pfizer tested “numerous” iterations of a stabilised prefusion F protein, eventually identifying a candidate that “elicited a strong anti-viral immune response in pre-clinical evaluations”.
On top of the RENOIR programme, Pfizer revealed in March 2022 that RSVpreF received “Breakthrough Therapy Designation” from the FDA for the prevention of “RSV-associated lower respiratory tract disease caused by RSV” in infants up to 6 months old by “active immunisation of pregnant women”.
The trial
Pfizer described how a “pre-planned, interim analysis” of the efficacy of RSVpreF, conducted by an external Data Monitoring Company (DMC), assessed protection against “RSV-associated lower respiratory tract illness (LRTI-RSV)”. Following a “positive result” of vaccine efficacy (66.7%), Pfizer was able to explore the “more severe disease primary endpoint of LRTI-RSV”. Vaccine efficacy of 85.7% was observed, defined by “three or more symptoms”. The DMC also suggested that the vaccine was “well-tolerated, with no safety concerns”. Thus, Pfizer intends to submit a Biologics License Application (BLA) to the FDA.
The RENOIR trial is a “global, randomised, double-bind, placebo-controlled study”. In August 2022 it had already enrolled around 37,000 participants. Participation will increase in the Southern Hemisphere to “accumulate cases during their first season”.
Dr Annaliesa Anderson, Senior Vice President and Chief Scientific Office, Vaccine Research and Development, said that Pfizer is “delighted” at this progress.
“Scientists and researchers have worked to develop RSV vaccines with little success for over half a century.”
She believes that these findings are an “important step” in the effort against RSV. Pfizer is prepared to work with the FDA and “other regulatory agencies” to ensure the vaccine is “available to help address the substantial burden of RSV”.
An article in npj vaccines in February 2024 considers the future of the adult vaccine landscape, using insights from interviews to “serve as a pivotal starting point” to enable industry participants to navigate an “anticipated surge” in “volume and complexity”.
“To unlock the societal benefits of this burgeoning expansion, we need to adopt a fresh perspective to steer through the dynamics sparked by the rapid growth of the global adult vaccine market.”
The authors reflect that vaccine innovation drew “significant attention” during the COVID-19 pandemic but was “already on the cusp of a groundbreaking renaissance”. For adult populations, integration of vaccine programmes is notoriously challenging, suggest the authors, who consider “low uptake, funding shortfalls, and operational hurdles”. Adult immunisation is a key theme for the Congress in Washington, so we explore the article here and invite you to join us in April to share your thoughts on the issue.
At a crossroad
“As the adult vaccine landscape rapidly evolves, we find ourselves at a crossroad where addressing the status quo of immunisation efforts is no longer an option but a necessity.”
The authors state that the COVID-19 pandemic “served as a stark wake-up call”, exposing the “fragmented nature” of adult vaccine infrastructure. The system that was revealed is “wholly unprepared for the impending rapid growth” in adult vaccines. While this may be a daunting situation, the authors believe that these challenges can be “catalysts for transformation”.
The article suggests that the “ongoing and accelerating transformation” in adult vaccines will be “propelled by the rise of RNA technology, thrusting us into a new era of digital vaccine”. Comparing RNA-based solutions with “traditional biologic counterparts”, the authors state that the former are “not constrained by the same production processes”, creating potential to “conceptualise innovative vaccine designs using a single manufacturing process”.
Time for a revolution
“The timing of this vaccine revolution is critical.”
Referring to an ageing global population, the authors identify calls for “more potent vaccines to safeguard health and wellness”. This is emphasised by the effects of vaccine-preventable diseases (VPDs) on the economy; VPDs account for an estimated 8 million to 10 million disease cases in the US alone, which result in “up to $34.9 billion in annual societal costs”. There is an “informal economy” consequence as well, as older adults play an “invaluable role” by offering childcare and financial and emotoinal support, which “cannot be quantified through economic analyses alone”.
However, the development of adult vaccines is not simple; future vaccines must be “tailored to different risk groups” to provide “optimal efficacy”.
Market research
The authors conducted a market research study with the US as a pivotal case study to understand the “evolving” adult vaccine market. From their results they identify challenges and weaknesses that, if neglected, may “quickly become overwhelmed in the face of an evolving and expanding industry”. The goal is to shift the “complacent” implications of the phrase “there is always next year” to an “urgent call for innovation”.
Evolution and growth
Recognising the importance of a paediatric “bias” in the mid-twentieth century, the authors state that the US has a “strong” paediatric immunisation programme with “clear guidelines, well-defined immunisation schedules, and school entry requirements”. However, for adult vaccines there are challenges like “limited awareness, accessibility, affordability, and vaccine hesitancy”.
Despite these challenges, the adult vaccine market is “experiencing rapid expansion” with a growth trajectory driven by increasing prevalence of VPDs in adults, technological advancements, and a “heightened focus” on preventative healthcare.
“Over the next decade, we anticipate a tripling in the number of approved vaccine products globally.”
There are 35 products currently available across 13 disease areas, but over the next 10 years this is predicted to grow to 100-120 risk-adjusted products over 40 different disease areas. Vaccine categories are expected to grow from “well-known diseases” and travel or endemic diseases to include nosocomial vaccines. Furthermore, there is a possibility that vaccines for “high unmet” need diseases like HIV will “enter the adult vaccine landscape”.
Alongside expanded offerings, the authors refer to “growing competition”. Four “historical leaders”, GSK, Merck, Pfizer, and Sanofi, may see “increased pressure” from new entrants and global players.
“Additionally, as best-in-class products likely will not be enough to capture the market, manufacturers are expected to distinguish themselves through differentiated portfolio offerings, rather than individual products.”
As more vaccines enter the market, vaccine schedules are “expected to undergo substantial expansion over the next decade”. Indeed, the phenomenon of “forced seasonality”, where non-seasonal vaccines are administered over a compressed period, could “pave the way for a convergence of campaigns for new vaccines with those of seasonal vaccines”.
“Such alignment could pose substantial challenges for immunisers and vaccination delivery sites as they grapple with the task of accommodating new patients and vaccines within a more limited timeframe.”
Breaking down barriers
The authors conducted a market research study of both qualitative and quantitative approaches to understand the “potential challenges and reactions to future states of the adult vaccine landscape”.
“Through interviewing and surveying key adult vaccine market stakeholders, we found that many stakeholders may not be fully cognisant of the impending wave of adult vaccines.”
This ignorance is largely attributed to an “absence of incentives to assess situations beyond the current fiscal year”, which then fosters “short-term thinking” and hingers the identification of “potential long-term effects” within the market. This could lead to “lack of preparation” and result in “missed opportunities”.
“The adult vaccine market has also seen a shift in focus to newer participants, such as the rise of alternative vaccination sites like pharmacies, aiding a decades long trend, which is expected to continue.”
While this change brings opportunities, it also presents challenges, such as “concerns” about pharmacists’ access to medical records and vaccination histories. To address this, the authors state that we need to build a “sense of trust” between pharmacists and physicians, which will be “paramount to the successful dissemination of future vaccines”.
Another consideration is the experience of a pandemic and how it may distort perceptions for the future; the authors emphasise the importance of remembering difficulties in distribution and looking forward to a “dynamic environment” that will demand “continued vigilance, flexibility, and readiness to embrace change”.
The adult population
Another challenge arises in considering the intended recipients of these vaccines. For example, patients were willing to receive “up to four” vaccines a year but preferred to limit administration to two per visit: one in each arm.
“The expansion of the adult vaccine market means that consumers will need to take more ownership of their vaccination schedules and records.”
Even if patients are keen to access vaccination programmes, the authors consider that “far too many in the US still suffer from unequal access to healthcare”. Disparities cause a divide in “actual health outcomes”. However, they recognise that apart from the “moral imperative” of “bridging the equity gap” there is a financial incentive: estimates suggest that eliminating racial disparities alone could save “over $90 billion” annually in “unnecessary medical expenses”.
“Unfortunately, our market research has highlighted that no stakeholder group is individually accountable for addressing vaccine equity. We found a significant gap in understanding and responsibility within the vaccine ecosystem, leading to a disconcerting reality: equity is falling through the cracks.”
What do the authors conclude?
“The adult vaccine market stands on the threshold of significant growth in the forthcoming years. Preparing to incorporate more vaccine into the existing ecosystem could lead to enhanced health and economic outcomes in the future.”
The article recommends “proactive solutions” that consider the “consumer and their choices”. What might this look like in your work? Do you agree with any of the arguments or findings in the article? We look forward to considering adult immunisations in greater detail during the Congress; are you joining us there? Don’t forget to subscribe for weekly insights.
An article for BMJ Global Health in January 2024 states the importance of moving in the direction of “global vaccine equity with shared goals, intermediate steps, and long-term advocacy goals”, with an emphasis on doing so “before the next pandemic”. Recognising that “vaccines are key to preventing and ending pandemics”, the authors state that COVID-19 “will not be the last pandemic” and invite countries to use lessons from their experience of it, as well as their responses to the HIV pandemics. They describe the HIV response as “at the vanguard of ensuring equitable access to rights-based services, to create shared goals and engage communities to increase access to and delivery of safe, quality vaccines”.
COVID-19 and inequality
Even though COVID-19 is known to have been a “leading cause” of morbidity and mortality globally, resulting in “almost 7 million deaths” by January 2023, many cases were undetected due to “widespread lack of diagnostic test availability”. Therefore, the human burden is underestimated. Although vaccines have “been essential” in reducing this burden, countries “scrambled” to access them, which meant that “the most effective vaccines largely went to countries in the Global North” at the start.
For example, the Africa region represents one-fifth of the global population but had only received 3% of all COVID-19 doses by 2021.
“While the number and types of vaccines delivered to the Global South have increased over time, countries in the Global South have been the most disadvantaged in obtaining access to the most effective vaccines.”
Vaccine equity
The authors consider “two central dimensions” for vaccine equity:
Access – are the vaccines a country has the most effective vaccines available? Are the prices for the vaccines affordable for the country?
Delivery – Does the country have a quality healthcare system, supply chain, and workforce to deliver the vaccines?
Even within countries, vaccines have been distributed “unequally”, usually to the disadvantage of the most vulnerable, including “people with disabilities, homeless populations, refugees, as well as those in prisons, crowded living conditions, and with precarious work conditions”. Furthermore, those living with HIV who are not virally suppressed are at “high risk” of COVID mortality. The article highlights that of the 38 million people who live with HIV, more than 25 million live in Africa, which has the lowest rates of COVID vaccination.
“While public health dictates that those at highest risk should be the highest priority to be vaccinated, one reason this did not occur is that individuals who had resources or were in positions of power were vaccinated first.”
This persists, despite recognition that, to limit mutations and further spread, we need to vaccinate a global majority. Therefore, the authors distil policy-level recommendations and actions for consideration by Global South country leaders.
“Given how little progress has been made to date, in an effort to ‘decolonise’ global health, countries in the Global South and CSOs may want to consider what actions to take now that will not solely depend on the goodwill of the Global North.”
Increasing access
Decentralise the production of vaccines, fostering the increased production of mRNA vaccines on many continents rather than relying on donations. The authors call for the development of a “transparent, web-based system” to monitor the supply chain that supports vaccine developers and manufacturers. They highlight that donations from the Global North are a “short-term, not perfect solution” that perpetuates dependency on donors.
Create a system of price transparency for vaccines. For example, COVAX is a public-private partnership founded to deliver COVID vaccines globally, but it did “not meaningfully” engage countries in the Global South or CSOs.
“Transparency of pricing could be a way to obtain the lowest price for low-income countries in the Global South, following the model established by UNICEF for childhood vaccines.”
Collect easily understandable, accessible, and transparent data on COVID vaccines. The authors suggest a website with the following information:
What is the effectiveness of different vaccines against which variant to prevent mortality?
Where are the different vaccines available?
Where is a particular vaccine useful given a country’s infrastructure?
Safety profile of the different vaccines
Cost per dose of vaccine in each country
Create demand for a new international legal framework that allows intellectual property (IP) rights to be waived quickly once a global pandemic is identified. Although the most effective vaccines with the fewest side effects were the mRNA vaccines developed by Pfizer and Moderna, US law “encourages grantees to protect their findings as IP”, to be sold to pharmaceutical companies which are unlikely to undertake development without profit guarantee.
“An ongoing global advocacy strategy by Global South governments, CSOs, and multilateral and bilateral organisations pressuring the Global North to engage in improved global vaccine equity is needed.”
A model for this could be based on HIV-focused efforts, as the authors highlight that the AIDS pandemic showed that “public advocacy leads to results”.
“We recommend that countries work simultaneously to both build their own mRNA vaccine production, supply, and expertise, as well as negotiating with pharmaceutical companies.”
Draw on the expertise of scientists in pharmaceutical companies around the world and other expert scientists globally who are willing to share and collaborate. Although mRNA vaccines are “new technology”, and access to this kind of expertise is “challenging”, the authors refer to Afrigen scientists receiving training and a US-South Africa-Thailand partnership to conduct manufacturing in line with GMP and share other scientific information.
Improving delivery
Create or strengthen public health systems that can deliver vaccines and other healthcare services throughout the lifespan that will lead to a reduction in morbidity and mortality.
“There is an ongoing need to create an adequate cadre of health workers, with sufficient remuneration and with the resources needed to succeed.”
Furthermore, specific laws might be required to protect healthcare workers and ensure fair working conditions. Donors can get involved by investing in “creating community demand and decision-making”. A “practical goal” for pandemic preparedness is the 7-1-7 target for detection, notification, and response: this allows primary care 7 days to assess a suspected outbreak, 1 day to notify public health authorities, and 7 days to implement effective responses.
Vaccinate strategically, vaccinating as many as possible, particularly those at highest risk, with available vaccines to reduce mortality. The authors highlight Vietnam’s use of non-pharmaceutical interventions in advance of vaccination campaigns and “massive diffusion of all media” until the country had access to vaccines.
Based on public health criteria, create an equitable system of prioritisation for gaining access to vaccines. The healthcare workers and providers must be “among the first to gain access” to lifesaving vaccines in a “functional” health system.
We recommend to either create and/or strengthen national regulatory agencies (NRAs) to appropriately regulate vaccines, ensuring that any manufacturing of vaccines meets GMP standards. Countries need transparent and effective NRAs, and where they do not have their own, they can “draw on regional regulatory systems” such as the Caribbean Regulatory System.
Identify credible, trusted sources of health information, promote health literacy and create a national scientific advisory committee to disseminate accurate and reliable information during a pandemic. Improved health literacy encourages an understanding of changing guidance in response to emerging data. All platforms that can be “interactive, trusted, and transparent” should be used and balanced with the “needs and concerns of the population”.
Foster transparent surveillance systems. Improving birth and death registrations and sharing these data can inform accurate pandemic information.
Conclusions
“A number of the interventions suggested as a way forward to move towards global vaccine equity may take varying lengths of time to institute, so therefore, it is critical to start now to take action for the future.”
The authors state that from a “moral ethical” position and the view of “reducing preventable mortality globally”, it is important that vaccine equity is a goal with “practical intermediate steps and long-term advocacy goals”.
“Scientific integrity, transparency, accountability, and clear communication will be key.”
How do you think these recommendations could be effectively implemented both in the immediate future and as we try to make pandemic preparedness a more established approach? Many of the issues that are explored throughout the paper will be considered at our Congress in Washington this April; are you joining us there? Until then, don’t forget to subscribe for more global health insights!
In a study published in The Lancet Regional Health – Europe researchers sought to “facilitate the selection of new RSV intervention programmes” through an assessment of cost and benefits to potential programmes. Through a dynamic transmission model, they were able to compare maternal vaccination (MV) to long-acting monoclonal antibody (la-mAB) therapy against RSV in England and Wales, calculating “impact and cost-effectiveness”. The findings indicate that both strategies could “substantially reduce the burden of RSV disease in the infant population”.
RSV: a significant global health problem
The authors state that respiratory syncytial virus (RSV) “remains a significant global health problem”, especially for infants under the age of 5, who are “particularly susceptible to severe RSV disease”. The age group represents an estimated 3.6 million hospitalisations and 101,400 deaths each year. Within this group, most of the severe disease is concentrated in infants under 6 months old, accounting for 33% of hospitalisations and 46% of deaths in children less than 5 years old.
Protection progress
The paper reflects that there has historically been only one licensed product for protection against RSV: the monoclonal antibody treatment palivizumab (Synagis), a “costly” intervention that requires monthly injections. However, recent progress has been made in the development of two new products: Pfizer’s maternal vaccine, Abrysvo, and Sanofi’s la-mAB, Nirsevimab.
The former is a bivalent prefusion F subunit vaccine that was effective at protecting against medically attended RSV disease during the first six months of life when administered to pregnant participants between 24- and 36-weeks gestational age. The la-mAB is an anti-RSV monoclonal antibody with extended half-life, targeting the surface F protein. It is 74.5% effective at reducing medically attended RSV disease up to 150 days after administration in neonates. Both have been licensed by the FDA.
Cost and benefit
The UK’s Joint Committee on Vaccination and Immunisation is the national decision maker for immunisation programmes and is informed by “clinical and operational considerations” as well as cost-effective analysis. Thus, if there are different products or programme options, assessments must analyse all programmes simultaneously. The study authors identify a “challenging question” arising from the similar efficacy but different delivery routes.
“Careful evaluation through mathematical modelling and cost-effectiveness is required.”
To answer the question, the study offers a “head-to-head cost-effectiveness comparison” of maternal vaccine and la-mAB programmes in England and Wales. It integrates a transmission model calibrated to data on RSV incidence and clinical trial data into an economic evaluation, which allowed the researchers to calculate the “optimal programme under a realistic range of purchase and administration costs”.
“We find that all large-scale programmes are effective at reducing disease burden, and when considering the population-level effects of both products, including their indirect effects, both are similarly effective at preventing RSV disease per dose. However, due to their presumed higher coverage, the la-mAB programmes prevent more disease than the maternal vaccination programmes.”
A noticeable shift
It is notable that, after the “reduction in RSV-related healthcare outcomes in infants” there was an observed “small increase” in health outcomes in the 1-year age group. This arises from an “increased age of first infection” due to a “higher proportion of susceptibles in the 1-year age group”.
“This shift is a consequence of introducing large-scale short-lived passive immunity into the population, instead of relying on active immunity that builds up an individual’s own protection.”
The age shift was “more pronounced” with la-mAB use, as the protection is longer lasting in comparison with the maternal vaccine.
“In CEA analysis [cost-effectiveness analysis], assuming low CCPA [combined cost of purchasing and administration] for both products, the la-mAB programmes emerge as the optimal choice due to their larger overall impact and favourable cost-effectiveness ratio driven by higher coverage.”
However, the authors call for consideration of “other implementation factors” such as feasibility of implementation and the CCPA of each product.
What do you think of the paper, and do you agree with the conclusions drawn from the analysis? Let us know if you intend to join us at the Congress in April to discuss these interventions and other strategies in greater detail! If you can’t make it, why not subscribe here?
In an article in December 2023, POLITICO claimed that “at least 215 million doses” of COVID-19 vaccines that had been purchased by EU countries during the COVID-19 pandemic have been thrown away. POLITICO’s analysis indicates that this has cost the taxpayer €4 billion, which is “almost certainly an underestimate”. Apart from this staggering waste of resources and money, questions will certainly be asked about the prioritisation of vaccines during the pandemic, and how EU countries were put in this position of excess while other countries had so little.
Greed to garbage
POLITICO states that since the approval of the first coronavirus vaccines in 2020, EU countries have received 1.5 billion doses, which translates to “more than three for every person in Europe”.
“Many of these now lie in landfills across the Continent.”
Using available data, POLITICO suggests that these countries have discarded an average of 0.7 vaccines per member of their population. Topping this “scale” is Estonia, which threw away more than one dose per inhabitant. Germany is close behind, having discarded the “largest raw volume of jabs”. However, the report emphasises that governments are “reluctant” to share the extent of their waste, which complicates the picture.
A significant bulk of the vaccines were purchased “at the height of pandemic” in 2021, when the EU was “scrambling” to secure doses. At the time, the EU forged its single biggest contract to purchase 1.1 billion doses from Pfizer and BioNTech.
“Both the size and timing of the agreement turned out to be problematic.”
POLITICO’s calculations are made from information shared by 19 EU countries, comprising both direct data supply and local media reports. Furthermore, the timeline is blurry, with some figures dating as far back as December 2023.
“The passage of time means the figures we received are conservative, with the real number of discarded vaccines likely much higher.”
The price to pay
The estimated value of these 215 million wasted doses is over €4 billion, although this is based on media reports on the vaccine prices. Beyond the cost of these vaccines, there is likely to be an additional financial burden as countries adjust to the “living with” stage; an example of this is that Poland and Hungary are facing legal action from Pfizer due to an “alleged failure” to uphold their end of the immunisation supply deals.
On the other hand, Romanian prosecutors have requested the lifting of immunity of former Prime Minister and Health Ministers, claiming “abuse of office” related to the purchasing of COVID-19 vaccines for the country. While these skirmishes unfold, a revised contract with Pfizer will be “locking” European countries into vaccine purchases until “at least 2027”.
What about the rest?
While the EU may be worrying about overflowing bins, the rest of the world might (rightfully) be feeling a bit resentful. This problem of waste is a symptom of great privilege and may come across as a slap in the face to countries that struggled to secure sufficient doses. Earlier this year Professor Stephen Griffin, Professor at the University of Leeds, commented that the “living with” COVID-19 approach could not be adopted by everyone:
“Richer countries with better healthcare systems that could afford the best vaccines had, and continue to have a clear advantage over others, many of which have yet to even complete primary vaccination programmes on any scale.”
Although we wonder whether anything can prompt the EU to recall the ratio of responsibility to privilege as it plans immunisation strategies, perhaps a hefty bill is a helpful reminder. Then again, money is the reason we find ourselves in this position in the first place.
How do you suggest that this tragic waste can be avoided in the future? What might the EU learn from past purchases? For more on vaccine and immunisation strategies, don’t forget to subscribe to our weekly newsletters here.
In a feature for The BMJ in November 2023 Hristio Boytchev reports on concern raised by “some experts” that Pfizer should have informed pregnant participants in a respiratory syncytial virus (RSV) vaccine trial that a similar vaccine trial was paused over a risk of preterm birth. While this has caused discontent for one group, other suggest that notification would have been “premature and caused unnecessary anxiety”. So, what should have been done?
The RSV race
Both GSK and Pfizer have been working on recombinant RSV F protein vaccines for administration during pregnancy with the goal of protecting infants against RSV. WHO describes human RSV as a “globally prevalent” cause of lower respiratory tract infection in “all age groups”, yet in younger children the first infection can cause severed bronchiolitis that “can sometimes be fatal”.
GSK shared in February 2022 that “following a recommendation” from the Independent Data Monitoring Committee it had “voluntarily paused enrolment” in the GRACE trial and two other trials investigating the potential RSV maternal vaccine candidate. 10 days after the first update, GSK confirmed that enrolment and vaccination had stopped.
“Further analysis to better understand safety data from these trials is ongoing, and the relevant regulatory authorities have been informed.”
Subsequent reports to the FDA Vaccines and Related Biological Products Advisory Committee in 2023 state that the safety signals were an “imbalance” in the proportions of preterm births and neonatal deaths between the vaccine and placebo groups. At the time, GSK did not have a “mechanistic explanation” for this. Indeed, Boytchev reflects that “experts think it might be unrelated to the vaccine”; the imbalance was “primarily observed” in LMICs and inconsistently after a peak. However, GSK continued investigations and stopped development.
What should Pfizer have done?
Following this, “opinion was split” among ethicists and researchers, who questioned whether Pfizer should have informed trial participants about the potential risk. For example, Western University’s Dr Charles Weijer told The BMJ that this would have been the right choice, calling “any failure” to update safety information data “ethically problematic”. Professor Dr Klaus Überla, University Hospital Erlangen, advised The BMJ that following the publication of results from the GSK trial, other vaccine studies should be “updated” to include the potential risk.
On the other hand, Professor Beate Kampmann, director of the Centre for Global Health at Charité University Hospital Berlin and a lead author of Pfizer’s Phase III trial publication, suggested that the GSK results were irrelevant to her participants, most of whom “were already in follow-up”. Indeed, she considered the context of the safety concerns different to her own trial.
“This was a very location specific and also transient finding, which remains poorly understood.”
