Safety is the threshold that all players who set foot on the COVID-19 track need to cross

Novavax finally saw hope of entering the U.

Achilles' Heel: Security, Security, or Security

Novavax's EUA application is based on a Phase III clinical data
.
The study explored the effects
of NVX-CoV2372 in the U.
S.
and Mexico from December 2020 to September 2021 with about 30,000 people.

In December 2021, the results were published
in the New England Journal of Medicine (NEJM).
In terms of effectiveness of prevention, NVX-CoV2372 did not disappoint – the overall protective power was 90.
4%, although there was a certain decline in people aged 65 years and older, at 78.
6%.

Since the study was conducted, the main variant of the new coronavirus was Alpha, not Delta and Omicron
, which are currently in the spotlight.
But an FDA briefing note states that "based on efficacy estimates in clinical trials of the vaccine, NVX-CoV2372 is likely to provide some meaningful protection against the coronavirus caused by Omicron, especially against more serious diseases
.
"

At the same time, the FDA is particularly concerned about the safety of
NVX-CoV2372.

In subjects who completed vaccination, 6 cases
of myocarditis / pericarditis were observed.
In terms of timing, 5 of them appeared within two weeks of vaccination; In terms of age group, 4 of them were young males
.
Only one case
was reported in the placebo group.

Through data analysis, the FDA concluded that cases of myocarditis/pericarditis were causally linked
to vaccination with NVX-CoV2373.
Given that the vaccine has a higher risk of heart disease than other competitors, the FDA asked NVX-CoV2372 to label this safety issue as an "important identified risk
.
"

Novavax did not agree to this approach
.
Subsequent statements pointed the finger at the FDA's lack of sufficient evidence to establish a causal link between the vaccine and heart disease
.

In addition, Novavax said that myocarditis/pericarditis can be seen in any large data database, especially in younger men
.
In the Phase III trial of NVX-CoV2373, the incidence of myocarditis/pericarditis in the vaccine group and placebo group was 0.
007% and 0.
005%, respectively, and after cross-comparison, Novavax believes that the occurrence of side effects is within the expected range
.

This rhetoric stands in contrast
to the fierce reaction of the secondary market.
On June 3, the day the FDA's briefing was released, Novavax shares fell as much as 20 percent
.

In fact, safety is the threshold
that all players who set foot on the COVID-19 track need to cross.

Taking the new crown mRNA vaccine as an example, the incidence of myocarditis/pericarditis in men aged 16-24 years in Israel was 1/6000 to 1/3000; the U.
S.
Vaccine Adverse Event Reporting System (VAERS) data showed that the incidence of men aged 12-24 years was 1 in 20,000 to 1/15,000
.
It should be noted that the use of data systems and the incidence rate vary greatly in different regions
.

In June 2021, the CDC Advisory Committee on Immunization Practices (ACIP) held a meeting to discuss myocarditis/pericarditis in young people vaccinated against COVID-19
mRNA.
The team ultimately believes that strategies to continue to support 2 doses of the mRNA vaccine for people of all ages continue to be supported
.

The COVID-19 recombinant adenovirus vaccine is also plagued by adverse reactions
.
In the first half of last year, Austria, Denmark, Norway, Iceland, Italy and other European countries stopped vaxzevria vaccination in Austria, Denmark, Norway, Iceland, Italy and other European countries because of the observation of thrombotic
cases after vaccination.
In May, in order to avoid thrombosis and thrombocytopenia syndrome (TTS), the FDA decided to limit
the use of Johnson & Johnson Ad26.
COV2.
S.

In other words, novavax may also have to spend a lot of effort
to monitor the subsequent adverse reactions of NVX-CoV2373 after entering the US market.
And once the risks outweigh the benefits, Novavax's commercialization journey could be hit hard
.

2

Faltering participants in Operation Warp Speed

Although the technical route is different, the beginning of Novavix's story is particularly similar to that of another Moderna that has completed "self-hematopoiesis" today: the same establishment for many years, the same has not launched a listed product, the same to eat the capital dividend of the first wave of the new crown epidemic, and even focus on the company's CEO level, both of which are also from the same business school background
.

If we go back to the early days of this global pandemic, Novavax is a highly anticipated "dark horse.
"
A February 2021 report by Barron's said Novavax had risen more than 4,300 percent over the past 12 months
.

In addition to market performance, to some extent, the official is also endorsing
it.
In May 2020, then-US President Donald Trump proposed "Operation Warp Speed", and Novavax, along with Pfizer, Moderna, and Johnson & Johnson, stood out from hundreds of pharmaceutical companies and was included in this plan, which was highly supported
.

The concept of "warp speed" is commonly found in science fiction and movies, and became known
to the public through Star Trek.
This technique uses compression or folding of space-time to enable faster-than-light travel
.
The U.
S.
government has named the vaccine program Operation Warp Speed, in the hope of shortening the routine and lengthy development cycle of the vaccine to within
a few months.

Novavix, which has been sucking up gold all the way, is not without skeptics
.
Previously, it has been pointed out that in Novavax's experience, the development of S proteins that are highly similar to naturally occurring S proteins, sufficient to stimulate an adequate immune response and stable enough to maintain their immunogenicity during manufacturing, packaging and distribution requires a question mark
.

But in March 2020, Novavax developed a recombinant S protein
named NVX-CoV2373.
Under laboratory conditions, antibodies produced by the NVX-CoV2373 protein can interfere with the binding of the S protein of the new coronavirus to the human ACE2 and block the viral infection
.

It's not enough
to have S protein.
The success of the recombinant protein technology route requires additional adjuvants to help stimulate a strong protective immune response
.
This has also become a big reason why Novavax lags behind its mRNA technology peers such as Moderna, which eliminates the need to develop additional steps
such as recombinant proteins and adjuvants.

Operationally, despite receiving $1.
8 billion from Operation Warp Speed, it took Novavax more than a year to start production, and the NVX-CoV2373 clinical data was much
later than that of Pfizer and Moderna.

The first Phase III clinical trials of NVX-CoV2373 were selected in the UK and South Africa
.
The effect of this study was even better than another phase III performance
later carried out in the United States and Mexico.
However, it has also been proven that due to the need for local data to push NVX-CoV2373 into the US market, Novavax had to lengthen the front line and open another clinical trial, slowing down the pace
of approval.

Novavax has said that it will apply for regulatory authorization for NVX-CoV2373 in the third quarter of 2021, and hopes to reach a production capacity
of 100 million doses per month and 150 million doses by the end of the third quarter and the fourth quarter of that year.
However, there have been repeated delays
in implementation.

According to Silvia Taylor, Novavax's senior vice president of global corporate affairs and investor relations, Novavax has established production sites around the world, initially planning to let different bases play a role
in different regulatory scenarios.
But then, the scheme was eventually changed to the uniform use of the production process and initial data
of the Serum Institute of India.

This series of mistakes has allowed Novavax's vaccine to miss the opportunity to
hit the market in 2021.
It was not until the end of 2021 that the WHO included NVX-CoV2373 (product name Nusuxovid) in the Emergency Use List (EUL), and since then, more than a dozen countries and organizations such as the United Kingdom, the European Union and Australia have also released it
.

After solving the capacity problem, the NVX-CoV2373 finally began shipping to the European market
in February this year.

3

Got a late episode? Novavax wants to say "no"

On May 9, Novavax announced its first quarter 2022 results
.
NVX-CoV2373 has been listed in many countries around the world, but Novavax's profits and revenue have not met market expectations, and the stock price fell nearly 20%
on the day.

Specifically, Novavax's first-quarter revenue was lower than Wall Street's expectation of $845 million, or $704 million, up 57.
5 percent
from $447 million in the year-ago quarter.
Among them, NVX-CoV2373 sales were $
586 million.

In terms of net profit, the past quarterly performance is also a historic breakthrough achieved by Novavax, reversing a net loss of $222.
7 million in the same period last year and a positive net profit
of $203 million.
However, the market expected the value to be $
213 million.

In the first quarter of 2022, Pfizer/BioNTech sales of the COVID-19 mRNA vaccine Comirnaty were $13.
2 billion, and sales of the Moderna covid-19 mRNA vaccine Spikevax were $5.
9 billion, while Johnson & Johnson had no spin-off disclosures
.

Jumping out of the disparity in data, Johnson & Johnson's approach is worth playing
.
In the financial report, Johnson & Johnson believes that the global covid-19 vaccine supply is oversupplied and the demand is uncertain, and decided not to provide covid-19 vaccine sales guidelines for the time being and stop the production of
new crown vaccines.
To be sure, this is also a reality that is becoming more and more obvious
.

On June 6, NBC reported that there was current waste
of COVID-19 vaccines.
Citing data released by the US CDC, from December 2020 to May this year, the United States wasted a total of about 82.
1 million doses of covid-19 vaccines, accounting for more than
11% of the total number of vaccines distributed by the federal government.

State health officials and pharmacies say the main reason is that the U.
S.
COVID-19 vaccine uses a multi-dose vial specification, which means that once the package is opened, all doses must be used up within a few hours or discarded
.
In addition, some say that the minimum order quantity for vaccines is so large that the quantity they have left exceeds demand
.

What's more, the problem doesn't just arise in the United States
.
Recently, European countries such as the United Kingdom, Denmark, and Switzerland have also begun to destroy expired COVID-19 vaccines
.
Moderna, Pfizer/BioNTech and the European Commission have revised their cooperation agreements to allow delays in delivery of COVID-19 vaccines that would otherwise be delivered as planned
.

Global vaccination rates are approaching an "absolute bottleneck" – according to our World in Data, more than 60% of the world's population currently completes a 2-dose routine dose
.

So, will the Nth dose "strengthening needle" be an incremental space? The industry still seems to be struggling with
this.

A study by the Israeli Sheba Medical Center showed that the preventive effect of the fourth dose of the new crown vaccine was "minimal", and the levels of immunoglobulin antibodies and neutralizing antibodies in the subjects were basically similar
to those of the third dose one month later.

The results of another trial, also in Israel, reached the opposite conclusion
.
One week after completing the fourth dose of COVID-19 vaccination, the subjects increased their antibodies against the Omicron variant by a factor of 8; Two weeks later, that number rose to 10-fold
.
Moreover, there are no new safety risks
to receiving a fourth dose of the vaccine.

Novavax did not respond directly to the above reality, but reiterated the different possibilities
offered by NVX-CoV2373 as a vaccine for the recombinant protein of the new crown.
When asked by VRBPAC about whether they have been exposed to people who are hesitant about existing vaccines, Filip Dubovsky, Chief Medical Officer of Novavax, said: "1 in 10 Americans has not been vaccinated against COVID-19, and we have not given them
up yet.
" ”

Even at risk of developing myocarditis/pericarditis, Novavax hopes to encourage injections for those who do not trust mRNA vaccines through more traditional recombinant protein vaccine technology
.
And, unlike the cold chain transport required for the COVID-19 mRNA vaccine, NVX-CoV2373 can be stored under normal freezer conditions, which is conducive to Novavax's subsequent introduction of the product to more regions
.

According to BioSpace, at this stage, about 76% of adults aged 18 and over in the United States have received 2 doses of the NEW CROWN vaccine, most of which are from Pfizer/BioNTech and Moderna, and about 27 million adults have not received any COVID-19 vaccine
.

In its first-quarter earnings report, Novavax also continued to show its full-year 2022 revenue guidance of $4 billion to $5 billion, which is similar to Refinitiv's forecast, which said that NVX-CoV2373 is expected to generate about $5 billion in sales
for Novavax this year.

In January 2022, the WHO noted that repeated vaccinations with vaccines developed with the initial virus may be "neither appropriate nor sustainable.
"
.
In addition to NVX-CoV2373, at the end of May, Novavax initiated a Phase III trial of the COVID-19 vaccine against the Omicron variant to validate a divalent vaccine (NVX-CoV2373/NVX-CoV2515
).
The study will last 10 months, and if all goes well, Novavix will achieve preliminary results
in the second half of 2022.

Novavax also revealed that in April, another combination of COVID-19/influenza vaccine achieved preliminary results in phase I/II studies, showing good tolerability and immunogenicity
.
Novavax said it plans to launch a phase II dose confirmation trial
by the end of this year.