Preliminary results suggest the strategy of immunizing with the SARS-CoV-2 spike protein is efficacious, but details are lacking, and the exact nature and duration of the effect is unclear.

Treatment Action Group (TAG) and AVAC welcome today’s announcement that preliminary data from the efficacy trial of Pfizer/BioNTech’s mRNA COVID-19 vaccine indicates a high-level of protection against COVID-19. Our organizations urge caution, however, given the very limited information that is available only through a company press release.

The manufacturers have reported that greater than 90 percent protection was observed in a preliminary, pre-scheduled assessment of confirmed COVID-19 cases that occurred at least seven days after trial participants received the second injection of the two-dose vaccine regimen. A total of 94 cases of confirmed COVID-19 were included in the analysis, suggesting that nine or fewer were among recipients of the vaccine.

The information was disclosed after an interim analysis by the trial’s Data Safety Monitoring Board (DSMB) and no further details or data were provided (according to reporting by STAT News, even the companies are not privy to additional information). No serious safety issues have been documented to date, but a thorough, independent review of all adverse events will be necessary prior to any marketing of the product. The DSMB has recommended that the trial continue as planned and the final efficacy analysis will be performed after 164 confirmed COVID-19 cases, which may become possible before the end of the year.

The US Food and Drug Administration (FDA) has requested at least two months of safety follow up after the second vaccination before considering an Emergency Use Authorization (EUA), and Pfizer’s CEO Albert Bourla said sufficient safety data to meet this requirement should be available by the third week of November. This is a bare minimum for any review, and TAG and AVAC call for these data to be evaluated by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) in December before any action is taken. At the recent VRBPAC meeting on October 22, several members expressed concerns about the implications of vaccine EUAs and suggested that expanded access programs would be a preferable means of providing emergency access prior to full approval.

The Pfizer/BioNTech vaccine is designed to induce immune responses against the SARS-CoV-2 spike protein, a strategy that is also employed by many other candidates that are in efficacy trials. This provides some cause for optimism that multiple other vaccines will prove efficacious.

However, many questions remain given the lack of details available. Pfizer/BioNTech must be maximally transparent in releasing full information and data sets from the trial as they become available. Among the issues that will need to be addressed:

• The exact details of the numbers involved, endpoints analyzed, and statistical findings including confidence intervals and p-values;
• Efficacy against the range of possible COVID-19 outcomes, from asymptomatic (but potentially transmissible) SARS-CoV-2 infections to severe COVID-19 disease;
• Efficacy across diverse populations, particularly those most vulnerable to severe COVID-19 such as the elderly and those with health conditions that may make COVID-19 outcomes worse;
• Efficacy in populations that have been omitted from most studies to date, including children and pregnant women;
• Full characterization of the safety profile;
• Identification of correlates of vaccine-induce immune protection (such as antibody responses);
• Investigations into why vaccination did not work in the study participants who acquired COVID-19;
• Duration of protection. Studies suggest that immunity to seasonal cold-causing coronaviruses is typically short-lived (~6 months to a year), and it will be important to conduct long-term follow up to learn whether regular re-vaccination may be necessary;
• Equitable vaccine distribution in the United States and globally. Factors that will need to be considered include cost, pace of production, availability of supply, and logistical considerations such as refrigeration (the Pfizer/BioNTech mRNA vaccine needs to be stored at -80° C until just before administration);
• Ensuring any EUA (if deemed more appropriate than expanded access by FDA) places specific requirements for continued data collection and clearly articulates the pathway and timeline for a full application for licensure; and,
• Implications for efficacy trials of other candidates, given that it may become inappropriate for participants to continue to receive placebos if an effective vaccine is available.

Today’s news offers hope that it will be possible to quell the COVID-19 pandemic with vaccination campaigns backed by strong public health measures. However, the data are still preliminary, and a safe, effective, and equitably delivered vaccine will require a great deal more verified, peer-reviewed data and regulatory decisions. Once a vaccine is available, equitable access depends on political will in the form of evidence-based messages, fully funded vaccination campaigns in all countries and communities, and a globally coordinated effort to ensure that supply and demand reflect need, not greed or nationalist responses. TAG and AVAC support the call for a people’s vaccine to made universally available to all at no cost.

TAG and AVAC are heartened by the news of the incoming US administration’s plans for dealing with the COVID pandemic and commend them for the decision to rejoin the World Health Organization (WHO) as soon as possible. We urge them to join multilateral efforts to ensure equitable global allocation and distribution of COVID-19 vaccines. No country in the world, including the United States, will end this pandemic with isolationist responses. The fact that the first report of COVID-19 vaccine efficacy emerged from a collaboration between a German and US company (the former founded by Turkish immigrants; the latter founded by German immigrants) underscores this point.

HIV prevention advocates following COVID-19 vaccines got not one but two pieces of scientific news in the past two days—both as welcome as the US election results announced over the weekend. The HIV Prevention Trials Network announced that injectable long-acting cabotegravir (CAB-LA) provided high levels of protection among cisgender women at risk of HIV; and Pfizer announced high levels of protection in its COVID-19 vaccine candidate.

Two trials, two injections, one bottom line: A product doesn’t protect if it’s not available. While neither CAB-LA for cisgender women nor the COVID-19 vaccine have published peer-reviewed results—as they must—planning for licensure and access must start now. More details about CAB-LA are here, and join HPTN’s webinar on Friday, November 13 at 7am EST to learn more about the results.

Read TAG and AVAC’s statement on the Pfizer announcement and find our key messages below:

• Pfizer’s early results are welcome news but they must be read cautiously as the information on the data is still limited and only available through a company press release.
• Current data do not yet support Emergency Use Authorization (EUA), and certainly not licensure. The trial’s continuation is essential.
• The US FDA has requested at least two months of safety follow up after the second vaccination before considering an EUA; this is a bare minimum for any regulatory review.
• When available, these data need to be evaluated by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC).
• Any EUA should place specific requirements for continued data collection and clearly articulate the pathway and timeline for a full application for licensure.
• The Pfizer/BioNTech vaccine is designed to induce immune responses against the SARS-CoV-2 spike protein, a strategy that is employed by most other candidates in efficacy trials; these early data provide some cause for optimism that multiple other vaccines may prove efficacious.

Resources for additional context on COVID-19 vaccines:

• A useful Twitter thread from Dr. Natalie Dean, a biostatistician at the University of Florida.
• A transcribed Q & A on the Pfizer results with Dr. Wayne Koff, CEO of the Human Vaccines Project.
• A short video from STAT offering a two-minute primer on the mRNA technology used in the Pfizer and Moderna vaccine candidates.
• To understand the process and strategic considerations around the regulatory process read AVAC’s Regulatory Approval Primer for Vaccine Advocates.
• And no matter how good the Pfizer candidate turns out to be when the data are complete and reviewed, the world will need multiple COVID-19 vaccines; check out AVAC’s cheat sheet on the pipeline.

Use these resources and others to stay informed and connected. Together, let’s make our way to a safe and effective people’s vaccine against COVID-19 that the world can trust and use.

This week, the American people elected Joe Biden and Kamala Harris as the next President and Vice President of the United States. This is a historic moment for many reasons, including the election of the first woman, first Black and first Indian-American person as Vice President.

AVAC marks this long-awaited, historic day as a victory for all who are committed to science, evidence, compassion, empathy, dialogue and diversity.

While we celebrate, we also acknowledge the enormous public health and global development challenges that the Biden-Harris Administration must address. AVAC looks forward to working with the incoming Administration, and with allies around the world, to secure health equity and justice for all.

As we move forward, AVAC calls for:

• Full, continued funding of the President’s Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria, with support and extension for PEPFAR’s robust data-driven approach and the broad, health systems and rights-focused work of both PEPFAR and the Global Fund.
• The immediate rescission of the Global Gag Rule, as a first step towards a human-centered, life-saving, rights-based approach to health within and beyond America’s borders.
• Recommitting full scientific and financial support to the World Health Organization.
• Restoring US and global confidence in the US Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA).
• Ensuring that the United States leads a science-based response to COVID-19, focused on reducing rates of infection and death among those most affected by the pandemic, whose vulnerability is often tied to the effects of systemic racism and inequitable health systems.
• Supporting global health efforts to ensure that COVID-19 specific funding builds robust multi-disease prevention, testing and treatment programs that address HIV, tuberculosis and malaria, and that advances responses to gender-based violence by financing and supporting community leaders leading the fight for change.

There is much to be done, but also much to celebrate. AVAC looks forward to participating in a rejuvenated and reenergized movement towards justice and health in the months and years ahead.

More than nine months into this new pandemic, we know that COVID-19 continues to have an enormous negative impact on many global health priorities, including HIV, TB, malaria and routine vaccine programs, as well as reproductive health. The WHO estimates that if significant efforts are not made to address the health care disruption caused by COVID-19, there could be an additional 500,000 deaths from AIDS-related illnesses, including TB, in sub-Saharan Africa in 2020–2021.

But these outcomes are not a foregone conclusion. We can already see how civil society, communities, and countries are developing and implementing innovative ways to combat COVID-19 without losing ground in other areas. Amref Health Africa, AVAC and Friends of the Global Fight have come together to document these success stories with a new project called Protecting Global Gains. You can see it online at www.protectingglobalgains.org and on Twitter at @hivpxresearch, @theglobalfight and @Amref_Worldwide. We hope you’ll amplify these stories on your own social media—and help us identify other stories that need to be told.

Protecting Global Gains showcases innovation to advance more resilient and sustainable systems for health. Our first featured story is Leap, a platform developed by Amref Health Africa, which is helping train community health workers in Kenya. Leap pairs technology with tried-and-true public health practice to address training needs in a public health emergency. Its potential benefits extend well beyond COVID-19.

We will regularly highlight innovative approaches that are helping communities. The site also houses resources and social media materials to equip advocates with data and messaging to demand changes to advance both emergency responses and long-term health priorities. If you have a story of innovation to share, let us know here.

We look forward to sharing more stories in the weeks and months ahead, hearing from advocates about these tools and joining together to protect global gains.

Mitchell Warren is AVAC’s Executive Director. This piece first appeared on Alan Whiteside’s blog.

Science, not politics, must lead to COVID vaccine approvals and delivery

COVID-19 has devastated communities and health systems around the world – but has created an historic global effort, leading to the unprecedented development of more than 165 potential vaccines against COVID-19. Equally impressive innovations are speeding vaccine testing within a rigorous scientific framework. Manufacturing and transportation capacity are being scaled up to distribute millions of doses of future COVID vaccines to those who need them most.

But developing COVID-19 vaccines at “pandemic speed” depends both on an unprecedented global research effort, and on innovative strategies to shorten the vaccine testing and distribution timeline. Each strategy should be weighed against relative risks and benefits, along with its potential to speed vaccine research. Speed is important, but not at the expense of ethics, safety, robust engagement, equitable access, and scientific rigor, including independent peer and regulatory review.

It seems every day brings an update – another vaccine enters into large-scale phase 3 trials; confusion about regulatory processes; concern about growing vaccine nationalism; and ever-present worry that politics will push researchers, developers, policy makers and regulators to move not just fast, but recklessly. Here is my list of key questions to try and make sense of it all:

1. Is one vaccine enough?

Simultaneous testing of large numbers of candidates across multiple vaccine platforms increases the chances of quickly finding a safe and efficacious vaccine. The current pipeline of COVID vaccines includes well over 150 candidates, with over 40 already in human clinical trials. Because of the extraordinary global interest in developing safe, effective and easy-to-manufacture COVID-19 vaccines as quickly as possible, the candidates represent a broad array of approaches – DNA, RNA, live-attenuated, inactivated, subunit and viral vector vaccines – some have been used for common current vaccines, while others are novel approaches. My organization, AVAC, created a COVID-19 Vaccine Pipeline Cheat Sheet. It offers advocates an at-a-glance view of the products, funders, research phase and considerations for some of the front-runner candidates, as well as refresher on the different platforms. (Editor’s note: this cheat sheet is highly recommended, it gives the basic information in an easy format).

2. How is vaccine development going so fast?

The traditional approach to vaccine testing runs preclinical and then Phase I, II and III studies in sequence, sometimes with gaps between each study. To speed timelines, some COVID-19 vaccine studies are advancing to the next phase of research as soon as data show the vaccine is promising and safe, even while the previous study phase is still underway. This accelerated approach has long been championed by AIDS and TB vaccine advocates – but those processes remain much slower with far fewer financial resources and much less pharmaceutical company involvement.

The COVID-19 vaccine response has ushered in a new era of collaboration in research and research funding. Based on models developed in HIV research, collaboratives such as the WHO-led ACT Accelerator, the US government’s ACTIV consortium and Operation Warp Speed and others are pursuing different approaches to speed COVID-19 vaccine development, by collaborating on COVID-19 vaccine science and funding. This includes advance purchase commitments, where public-sector and philanthropic funders negotiate a price and plan to purchase and distribute vaccines, before the vaccine testing process is completed. There are both risks and benefits to this expedited research – check out our guide here.

3. But is it safe?

Going fast cannot mean a license to go recklessly – the safety of those people receiving a vaccine at any point must be the primary priority, for any and every vaccine, and especially given the high political profile of COVID-19. Every trial has an independent Data Safety and Monitoring Board (DSMB) that reviews the data on an ongoing basis. Given the current politicization, the nine leading pharmaceutical companies recently signed a pledge to follow the science in development of COVID-19 vaccines, and promise to prioritize safety. But don’t just believe the companies – at least two of the most promising vaccine candidates in large-scale trials have paused their trials to investigate serious adverse events seen by the DSMB – these pauses are not uncommon and actually give us confidence that safety is, indeed, being put first.

4. Can I trust the process?

Regulatory review by agencies such as the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA) is traditionally a methodical, rigorous process that can take many months. HIV advocates played a vital role in speeding review of new treatment and prevention options for HIV and AIDS. This created the compassionate use and emergency access systems being used today to help ensure rapid access to potential prevention and treatments for COVID-19. But regulatory review can only be accelerated to a point; it must be based on adequate data and allow for the thoughtful, informed and unbiased decision-making that is central to the product approval process. The FDA is currently under the most scrutiny given US politics, and here is our Regulatory Approval Primer for Vaccine Advocates. And my colleague Uché Blackstock of Advancing Health Equity and I recently wrote this commentary about Science, not politics, must lead to COVID vaccine approvals.

5. If we build it, will they come?

In our commentary, Dr. Blackstock and I argued why undue political pressure to speed the introduction of COVID vaccines is bad news, and threatens scientifically proven systems to protect public safety and research integrity – for COVID vaccines and for the vaccine enterprise generally. The consequences of any vaccine approval that appears to have been influenced by politics would be particularly grave for Black and Latinx communities in the US and marginalized populations around the world, who have real reasons to distrust both politicians and drug testing processes, and who are also at significantly increased risk for COVID infection and illness.

The rapid development of safe and effective COVID vaccines could help end this pandemic and strengthen worldwide faith in vaccines. But that can’t happen unless we take the signals of diminishing public faith in the process seriously and eliminate any sign of political interference in vaccine testing or approval. To protect health around the world, and advance health equity, we must insist on a COVID vaccine effort that is fast, transparent, thorough and safe, and guided by science, not politics.

6. Will the first one be the best one

The world will undoubtedly need more than one COVID-19 vaccine, especially to ensure enough manufacturing capacity. Plus, the first product to have a regulatory approval may not be the best – or the easiest to manufacture, the cheapest, or the easiest to deliver. But the first approval may challenge how to design and conduct future trials, as a placebo-control may not be ethical once we have an initial approval. Again, HIV researchers and advocates have grappled with these challenges for decades, so this is not new, nor a bad thing, but adds a degree of complexity to our future.

7. Who should get the vaccine? And who decides?

As complex as vaccine research and development is, vaccine delivery is even more so. In many respects, any regulatory approval is not the beginning of the end, but, rather, the end of the beginning. This is especially true for a vaccine that will be needed by billions of people. There many logistics questions: Are there enough glass vials and needles? Can companies make such large volumes in a matter of months? But who will buy these vaccines? And, most importantly, who will ensure that there is equitable distribution?

Already, many wealthy countries have made advanced market commitments to buy billions of doses. This buying power has led to concerns of “vaccine nationalism” and crowded out any potential for equity and public health strategy. As we know too well, COVID anywhere can quickly become COVID everywhere. WHO, GAVI and CEPI have joined efforts to create the COVAX Facility to, hopefully, mitigate against these risks and ensure global equitable access.

8. A vaccine is essential, but not sufficient

Even as we look towards a safe, effective, affordable and accessible COVID-19 vaccine sometime in 2021 (we hope), we already have critically important public health measures available today can help reduce the global burden – wear a mask; wash your hands; remain physically distant (while socially connected); and contact tracing. These measures will be just as important even when we have a safe and effective vaccine, while the world grapples with delivery challenges.

This is not unique to COVID-19; we have important lessons from 40 years of HIV – we need a comprehensive, integrated and sustained response, even if we had a vaccine (which, sadly, we still don’t) and especially when we don’t. We must act with urgency to develop vaccines because they are essential; and we must act comprehensively since a vaccine alone won’t be enough.

This post first appeared in Science Speaks. Uché Blackstock, MD, is the Founder & CEO of Advancing Health Equity, and Mitchell Warren, is the Executive Director of AVAC.

COVID-19 has devastated communities and health systems around the world – but it has also created an historic global effort leading to the unprecedented development of more than 165 potential vaccines against COVID-19. Equally impressive innovations are speeding vaccine testing within a rigorous scientific framework, while manufacturing and transportation capacity are being scaled up to distribute millions of doses of future COVID vaccines to those who need them most.

These advances require scientific collaboration and logistical coordination on a scale never seen before, and enormous investments of private and taxpayer money. All of that hard work, innovation and investment is endangered, however, if the public loses faith in a critical step in the process: the independent, unbiased review by regulatory agencies, such as the US Food and Drug Administration, of data demonstrating that a vaccine is safe and effective.

Vaccines are among the most powerful tools we have to reduce health disparities and advance health equity – but only if they are trusted and used. Government approval of any potential vaccine must be based on a process that is transparent, scientifically rigorous and free from political pressure. This is especially true as misinformation and conspiracy theories about vaccines circulate, and public confidence in vaccines falls. The consequences of any vaccine approval that appears to have been influenced by politics would be particularly grave for Black and Latinx communities, who have real reasons to distrust both politicians and drug testing processes, and who are also at significantly increased risk for COVID infection and illness.

That’s why it’s particularly worrying that politicians are wading into the vaccine testing and approval process. In the United States, government officials, perhaps with the November election in mind, are discussing granting emergency approval to one or more COVID vaccines as early as October – well ahead of the completion of essential Phase III vaccine testing. Concerns over the potential political manipulation of the vaccine approval process are so grave that last week nine pharmaceutical companies issued an unprecedented public pledge that they would not seek approval of any vaccine without extensive safety and effectiveness data.

How the US approaches vaccine approval will have global implications. FDA has provided a gold standard in the review and approval of drugs and vaccines – so much so that its decisions are often adopted by other countries. The idea that political pressure could lead FDA to alter its vaccine approval standards should send shockwaves not only through the US, but through global health systems as well.

The rush-to-approval dynamic is not limited to FDA, however. The Chinese military began using a COVID vaccine in July, long before advanced testing was complete. And in Russia, the release of a vaccine that has not undergone critically important Phase III testing has produced broad concern, with only 24 percent of physicians there saying they would give it to their patients.

Large Phase III studies are the only way to determine how well potential vaccines work, including whether they produce side effects unnoticed in smaller studies. To be truly effective, those studies must enroll not only enough people, but also the types of people who are most affected by COVID-19, including older people, people of color, and people with illnesses that may make them particularly susceptible to severe disease.

Any reliable vaccine study must also meet clear criteria, published in advance, for when and how the study is stopped. And all data for any prospective vaccine must be peer-reviewed and published in a transparent process that gives the public unshakable faith that the vaccine is being approved for scientific, and not political reasons.

Global efforts to speed COVID vaccine testing could produce a successful vaccine faster than any previous effort. Testing timelines can only be accelerated to a certain point, however, before we lose vital knowledge about how well a vaccine really works. The Russian example proves that vaccines won’t be used if people don’t understand or trust the testing and approval process.

That doesn’t mean that politicians will stop pressuring researchers and regulators to accelerate testing, sometimes with their own political fortunes in mind. This was most recently evidenced by the US Health and Human Services Secretary’s troubling memo which bans FDA (and other health agencies) from signing new rules regarding medicines. But it does make it more important than ever that researchers, regulators, public health professionals and community advocates raise our voices to prevent the politicization of science.

We’ve already seen the power of public pressure to compel product developers to publish their data analysis plans, stopping rules, statistical assumptions, and the membership of their independent review boards. Now that same energy should be focused on product developers, the FDA, and HHS to ensure that Phase 3 trials are able to accrue adequate safety and efficacy data before any decisions regarding approval are made.

Detailed guidance for COVID vaccine developers, issued by FDA in June, provides a roadmap for advocates to monitor and evaluate the vaccine approval process. Organizations such as AVAC have produced materials to help advocates and the public understand both the innovations that are helping to speed safe testing of COVID vaccines and the essential steps that must be completed before any COVID vaccines should be approved and licensed.

The rapid development of safe and effective COVID vaccines could help end this pandemic, and strengthen faith in vaccines worldwide. But that can’t happen unless we take the signals of diminishing public faith in the process seriously, and eliminate any sign of political interference in vaccine testing or approval. To protect health in the US and around the world, and advance health equity, we must insist on a COVID vaccine effort that is fast, transparent, thorough and safe, and guided by science, not politics.