Easy for you, easy on them

Todd Wolynn (TW): Hello everyone. It is a pleasure to be here with you today. My name is Todd Wolynn and I’m a pediatrician and Co-Founder of Kids Plus Pediatrics in Pittsburgh, Pennsylvania and Co-Founder of the nonprofit, Shots Heard Round the World. I’m happy to be here because as a pediatrician, immunizations are the cornerstone of preventative care. We’re looking forward to discussing the Novavax COVID-19 vaccine today, but first, I’ll ask my colleagues to introduce themselves. 

Jaime Fergie (JF): Hello, my name is Dr. Jaime Fergie. I’m the Director of Pediatric Infectious Diseases at Driscoll Children’s Hospital in Corpus Christi, Texas. I am the Medical Director for the Global Institute for Hispanic Health. 

Stefan Gravenstein (SG): Hi, I’m Stefan Gravenstein. I’m the Director of the Division of Geriatrics and Palliative Medicine at the Alpert Medical School of Brown University in Rhode Island. I would like to disclose that I receive funding from most of the vaccine manufacturers and I do vaccine research in older adults. Todd… 

TW: Jaime and Stefan, I’ve really been looking forward to this conversation with you today. A key concern for us healthcare providers is how to continue to help protect our patients from infectious respiratory diseases like COVID-19. Having seen the unprecedented impact of the COVID-19 pandemic, vaccination remains a critical public health tool for the prevention and control of infectious disease outbreaks. As we shift to an endemic landscape, what are your thoughts on the importance of reinforcing the benefit of being immunized with your patients? 

SG: First, there is a need to help patients understand the risk/benefit. By that, I mean there is a need to understand the benefit of vaccinating versus the risk of not vaccinating. The continuous evolution of the SARS-CoV-2 virus represents a significant burden that affects millions of people nationally every year and it impacts public health in general. The reality is that people may want to forget COVID-19 and live as if it no longer exists, but really we can’t. 

JF: Let’s remember, the goal of vaccines is to decrease illness and, in particular, healthcare-associated encounters such as ER visits, hospitalizations, ICU admissions, and death. As clinicians, we have seen that the response to the COVID-19 pandemic exemplified how the development of vaccines against complex, challenging infections has impacted public health. 

TW: I think we can all agree to the potential lifesaving benefits that vaccines are designed to provide. And as vaccines continue to evolve, it is important for us as healthcare professionals to continue to educate ourselves and our patients about the impact that vaccines may have. 

SG: You know, now is probably a good time to talk about the Novavax COVID-19 vaccine. I have noticed a lot of misleading information about COVID-19 and the vaccine options available. After all, these vaccines have been shown to help prevent severe disease and hospitalization. What are your thoughts around why physicians may want to offer the Novavax COVID-19 vaccine as an option to patients? Jaime, can you explain a bit more about how the Novavax vaccine works? 

JF: The protein-based vaccine platform is a welcome addition to the COVID-19 vaccine market. The protein subunit platform is well-established, having been used in other vaccines like hepatitis B and influenza vaccines. Novavax has also added its proprietary adjuvant, Matrix-M™, to the formula to enhance the immune response. Matrix-M is derived from saponins, which are naturally occurring compounds from the Chilean soapbark tree. Having this vaccine available in the office may make the difference between whether someone decides to get vaccinated. 

TW: Jaime, one of the attributes of the Novavax vaccine that I see working well in my practice is that it incorporates well with existing workflow and planning processes for providers. However, before we get into my thoughts on implementation and integration, let’s first dig a little deeper into how the vaccine platform works. 

JF: Well, Todd, first of all I think we have to mention that this is a non-mRNA option built on a well-established protein subunit platform. 

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The vaccine is composed of purified full-length SARS-CoV-2 recombinant spike protein that is stabilized in its prefusion conformation. 

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The addition of the saponin-based Matrix-M adjuvant facilitates activation of the cells of the innate immune system, which enhances the magnitude of the recombinant spike protein-specific immune response. 

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The 2 vaccine components elicit B- and T-cell immune responses to the recombinant spike protein, including neutralizing antibodies, which may contribute to protection against COVID-19. 

JF: A key question we should address that a lot of clinicians will want to know is, “How effective was the Novavax COVID-19 vaccine in clinical trials?” 

SG: Overall to date, the Novavax COVID-19 vaccine has been studied in clinical trials in approximately 45,000 participants from around the world. The effectiveness of the formula is based on the effectiveness of the original, monovalent Novavax COVID-19 Vaccine and the immunogenicity of the monovalent Omicron BA.1 and Omicron BA.5 vaccines. The safety profile is also based on the original, monovalent Novavax COVID-19 vaccine as well as the unapproved monovalent/bivalent vaccines. 

SG: Let’s take a closer look at the phase 3 PREVENT-19 trial, which evaluated the primary vaccine series. This was a multicenter, randomized, observer-blinded, placebo-controlled study in the United States and Mexico. Participants were stratified by age into 2 groups—18 to 64 and those 65 years of age and older—and randomized to receive the Novavax COVID-19 vaccine or placebo. 

PREVENT-19’s expansion trial used a similar design and evaluated the primary series in participants 12-17 years of age. 

A key inclusion criterion allowed for participants with clinically stable underlying comorbidities, as well as those with well-controlled HIV infection. The exclusion criteria excluded participants who were significantly immunocompromised or pregnant or breastfeeding, and/or had a history of laboratory-confirmed, diagnosed COVID-19. The immunocompromised exclusion included immunodeficiency disease, chemotherapy for active cancer, chronic immunosuppressive therapy, or if they got immunoglobulin or blood-derived products within 90 days. 

JF: The most important finding of the study was the primary endpoint with the vaccine. The vaccine achieved its primary endpoint, demonstrating efficacy in preventing symptomatic mild, moderate, or severe COVID-19, starting seven days after the second dose. 

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90.4% efficacy was observed in adults aged 18 years and older. 

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And 78.3% efficacy in adolescents aged 12 to 17 years. 

JF: There was also a post hoc analysis of the phase 3 trial examining COVID-19 hospitalizations related to then-circulating strains of the SARS-CoV-2 virus. In this analysis, no COVID-19 related hospitalizations were observed among Novavax COVID-19 vaccine recipients and 4 hospitalizations occurred among placebo recipients. These findings are subject to limitations, including the fact that vaccine efficacy estimates may have been impacted by the low number of observed events, as well as the fact that behavioral restrictions then in use may have successfully reduced infections and hospitalizations during the study, and the exclusion of key demographics, such as participants with certain underlying health conditions. 

I think many healthcare providers are also asking, “How long are my patients going to be protected?” Stefan, what do you think is the best way to answer this question? 

SG: It's hard to answer that question clinically because the virus is changing 

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But we do know immunologically because that was addressed specifically in the study. What we can talk about is in the follow up assessment of the PREVENT-19 study, the antibodies remained elevated for up to 11 months in participants who completed the primary vaccination series with the Novavax COVID-19 vaccine. 

JF: Todd, before we dive into the safety data, when you consider the efficacy data, what key points do you find most clinically relevant for your patients, and how do you communicate the benefits of this vaccine to them? 

TW: The efficacy data support offering the Novavax COVID-19 vaccine to appropriate patients. The data that stand out to me are 90.4% efficacy against COVID-19 in adult clinical trial participants. In addition, with analysis of secondary endpoints in the clinical trial, the vaccine showed 100% protection against moderate-to-severe illness from virus strains that were circulating at the time of the study. 

TW: Additionally, the vaccine showed antibody levels after the primary series vaccination remained elevated at 11 months. 

JF: I would agree that those are really key points in terms of the vaccine’s efficacy. Now, shifting gears for a moment, let’s look at some key points around safety and look at the adverse reactions that were reported in the pivotal clinical trials. 

SG: It’s been received by millions of people worldwide. I’ve received many questions about the occurrence of myocarditis and pericarditis and according to the data, although rare, cases of myocarditis and pericarditis have been observed following the receipt of COVID-19 vaccines used in the US. Clinical trials data provide evidence for increased risks of myocarditis and pericarditis following administration of the Novavax COVID-19 Vaccine, Adjuvanted.  

JF: Looking a little deeper, in the primary study series, among participants aged 18 through 64 years, the top 3 most common solicited adverse reactions of any grade after the first dose of Novavax COVID-19 Vaccine, Adjuvanted were 

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• injection site pain/tenderness,
• fatigue/malaise,
• and headache (60.5%, 30.8%, and 26.2%, respectively) 

For the second dose, the 3 most common solicited adverse reactions were 

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• injection site pain/tenderness,
• fatigue/malaise,
• and muscle pain (80.8%, 58.3%, and 50.7%, respectively) 

SG: Focusing on participants aged 65 and older. Patients in this age group in the primary phase 3 study experienced lower rates of any grade injection site pain and tenderness, headache, fatigue or malaise, muscle pain, joint pain, and nausea or vomiting compared with patients aged 18 to 64 years in the same study. 

SG: Todd, for the primary series, how did the safety profile differ for younger patients aged 12 to 17 years? 

TW: Well, the safety profile for younger patients aged 12 to 17 years closely mirrored that observed in the primary study series for patients aged 18 to 64 years. 

SG: Thanks Todd. We would also like to note that unsolicited adverse events such as chills, injection site pruritus, hypersensitivity reactions, lymphadenopathy-related reactions, and decreased appetite have been reported following the administration of the Novavax COVID-19 vaccine. 

TW: So now that we’ve covered some of the aspects of what can be expected from a safety and efficacy standpoint, let’s look at the Novavax COVID-19 vaccine dosing recommendation and route of administration. 

JF: The vaccine is available as a single 0.5 mL dose administered intramuscularly for individuals 12 years of age and older You know, as clinicians we hope that everyone eligible has been vaccinated, but how should the Novavax COVID-19 vaccine be administered to individuals who have not been previously vaccinated with any COVID-19 vaccine? 

TW: That’s an issue. Well, we do our best, but unfortunately, the number of people who choose not to get vaccinated is an issue. Perhaps with the opinion to receive a protein-based vaccine, we will be able to continue to increase the numbers of individuals we help protect against COVID-19. When this situation occurs, those persons should receive 2 doses of the Novavax COVID-19 vaccine, 0.5 mL each, 3 weeks apart. I’m sure you would both agree that a prioritized group to immunize and help protect in the minds of healthcare professionals is certainly the immunocompromised. 

How should we approach this patient population? 

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SG: Yes, this population is always top of mind due to their vulnerable immune systems. It is important to know that for individuals with certain kinds of immunocompromise, such as those who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise, an additional dose may be administered at least 2 months following the last dose of a COVID-19 vaccine. Additional doses may be administered at the discretion of the healthcare provider taking into consideration that person’s personal clinical circumstances. 

JF: It goes without saying that to help ensure we are good stewards of public health we must carefully and responsibly manage the well-being of the populations we serve. The overview of the vaccine’s dosing and administration was certainly helpful. 

Todd, you brought up earlier the challenges that clinicians encounter when integrating a new vaccine into a clinical setting. This is a challenge that providers face especially when it comes to storage requirements. I am hospital-based so this is not something I directly deal with, but I know this is certainly an issue for my colleagues in office-based practices. Can you shed some light on this topic and how the Novavax COVID-19 vaccine may be integrated into the clinical setting? 

TW: Well, as immunizing providers we are tasked with making sure that there is proper storage space and that adequate, recommended temperature control is maintained for the vaccines that we stock in our practice. In addition, we then must educate our staff and those that administer vaccines regarding dosages that should be given to patients. There can often be variance in the amount administered based on varying factors such as age and weight. Educating my staff about the Novavax vaccine is easier because it’s one dosage strength for all authorized uses. In my experience, this simplified dosing may also lessen confusion. 

JF: In your practice, how does the Novavax vaccine fit within the workflow? 

TW: One thing to think about when integrating new vaccines, especially in a busy practice, is efficient workflow. With the Novavax vaccine, there is no dilution, no mixing, and no thawing required. 

SG: I am sure your staff are happy to know that the Novavax COVID-19 vaccine has these features. It also sounds like that could alleviate additional waiting time for your patients as well. 

TW: Yeah, there is nothing like walking into an exam room when a patient has been waiting there for a long time. 

JF: Todd I understand that these are important points for practices administering this vaccine. I think this speaks to the simple dosing, storage, and handling of the Novavax COVID-19 vaccine, making it a convenient option to have in clinical practice. I would think this could create a more streamlined COVID-19 vaccination process for patients and providers. 

TW: We’ve talked about information that can help support the Novavax vaccine as a choice for patients and providers. I’m curious, what stands out to you when you think about information that is important to share with patients inquiring about the Novavax COVID-19 vaccine? 

JF: I’d speak to the fact that it is the only non-mRNA vaccine option authorized in the United States. It represents another choice in the vaccine landscape. In addition, the protein-based technology may be familiar as it has a similar approach used in some influenza and hepatitis B vaccines. 

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SG: Yeah, and we should continue to communicate that in clinical trials, the vaccine had 90.4% efficacy in adults aged 18 and older and 78% efficacy in adolescents aged 12 to 17 years. In addition, the Novavax vaccine showed 100% protection against moderate and severe disease in clinical trials. 

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There is also a demonstrated safety profile evaluated globally in approximately 45,000 adults and adolescents. 

TW: Those are great takeaways. I think communicating those points to patients is still critically important. COVID-19 has not gone away, but growing fatigue and hesitancy around immunization can be a deterrent to COVID-19 vaccination. The CDC recommends that individuals 6 months of age and older get vaccinated, but there are still many individuals who will not get vaccinated. What other information do you think is important to share with patients or your colleagues? 

SG: Well, I’m often asked about the type of patient for whom I would suggest the Novavax vaccine. Because my research focuses on the geriatric population, I feel that they are appropriate for consideration as is anyone interested in receiving it and for whom it is indicated. 

Other factors to consider: 

• Comorbidities, especially those with cardiac comorbidities and pulmonary conditions 
• Older age [like I said] 
• Immunocompromised patients 

Why don’t we look at an example of a hypothetical patient. 

This patient received an mRNA COVID-19 vaccine primary series in 2021. And then they tested positive for COVID-19 several months ago, so she had to take time off work. She doesn’t want COVID-19 to impact her work again but doesn’t see the point of receiving additional COVID-19 vaccinations. 

It is also apparent that she has read some misleading media information online about mRNA vaccines and is now hesitant about receiving another one. 

First, I’d want to explore the patient’s hesitancy about further vaccination in general as there can be many reasons for this such as the misleading information, lack of information, fear about side effects, and so on. This can be challenging to unravel because a patient’s thoughts around vaccination are going to be influenced by a variety of things that they have read, heard, or experienced. The key is really education that there are 3 options for COVID-19 vaccination right now. I would recommend the Novavax vaccine to this patient as a protein-based option and emphasize that it was developed using a well-established technology used for some flu and other vaccines. 

JF: You could also note that the SARS-CoV-2 virus that causes COVID-19 mutates, and the COVID-19 vaccine primary series she received 2 years ago may not have been designed to help protect her against the current circulating variants. We are always looking at changing variants and how to develop vaccines that are effective. 

TW: Yes, that’s a great point. After reviewing all this, Jaime and Stefan, it has been wonderful to have the time and opportunity to discuss the Novavax vaccine with you today. 

TW: I’m sure that our viewers may have questions, so with the remaining time, let’s open up the conversation to them. And I have questions right here. So, let’s take a shot at these. 

TW: So, [as I looking through], here’s a question: what is different about the Novavax vaccine? Jaime, would you like to answer this one? 

JF: Sure. It is the only non-mRNA, it’s a protein-based vaccine authorized in the United States. The protein subunit platform is well-established, having been used in other vaccines like hepatitis B and influenza vaccines. 

TW: Okay, we’ve got a lot of versions of this. So, why should I give the Novavax COVID-19 vaccine to my patients? 

I’ll take this one. So, people who are up to date on their COVID-19 vaccines have a lower risk of severe illness, hospitalization, and death from COVID-19 than people who are unvaccinated or who have not completed the doses recommended for them by the CDC. As providers, we recommend getting a vaccine no matter what. If you have patients who are hesitant about getting vaccinated, the familiar platform offered by this protein-based vaccine could make the difference. 

TW: Alright, let’s see if you guys are ready for another. Is the vaccine safe for my patients? Stefan, what do you have to say to this? 

SG: Sure. We have data from some 45,000 adults and adolescents formerly studied in clinical trials. In the primary series study, among participants aged 18 through 64 years, the 3 most common solicited adverse reactions after the first dose of the Novavax COVID-19 vaccine, were injection site pain/tenderness, fatigue/malaise, and headache (that’s 60%, 31%, and 26%, respectively). 

For the second dose, the 3 most common solicited adverse reactions were injection site pain/tenderness, fatigue/ malaise, and muscle pain (81%, 58%, and 51%, respectively). For people with a history of severe allergic reaction to the vaccine or any of its ingredients, the Novavax COVID-19 vaccine, is contraindicated. There isn’t enough data for pregnant women to inform vaccine-associated risks in pregnancy. For women who are breast-feeding, it is not known if Novavax COVID-19 vaccine is excreted in human milk. 

TW: Okay, I have one. I like this one. I’m a pharmacist, why should I stock the Novavax vaccine? 
I’ll take this one. Simple storage for convenient vaccination. With the Novavax vaccine, there is no dilution, no mixing, and no thawing required. This should not be frozen, so there is no freezer storage needed and this provides yet another great choice for COVID-19 vaccines. 

TW: Alright, let’s go with this question. What are your thoughts on coadministration of flu and COVID-19 vaccines? Stefan, would you like to answer this one? 

SG: Sure. In a recent JAMA Network Open paper, researchers looked at this question and found that immunogenicity and safety were not substantially different, supporting coadministration of the COVID and flu vaccines. Also, the CDC agrees that getting a flu vaccine and COVID-19 vaccine at the same visit is recommended if the patient is eligible and the timing for each vaccine is right. 

TW: Okay. Let’s go. This will be our last question that we have time for. What about myocarditis, which was seen in the pivotal trials? Stefan, would you like to answer this question? 

SG: Sure. Cases of myocarditis and pericarditis have been observed following the receipt of COVID-19 vaccines, including following administration of the Novavax COVID-19 Vaccine, Adjuvanted but these are rare. 

TW: It’s been great working with you guys. That’s all the time that we have today. Thank you for your time and your attention.