COVID-19 vaccine frontrunners: who are they (UPD)

Who are the vaccine frontrunners and how promising are their developed prototypes – that’s what we’re going to discover

COVID-19 vaccine

COVID-19 vaccine frontrunners: who are they. Source: pexels.com

Citizens of the whole world have held their breath waiting for the COVID-19 vaccine. A few globally recognized companies have committed to providing a panacea to the global madness caused by this vicious new virus. They are heavily subsidized by governments and private entities alike since everyone wants the pandemic to end. There are currently 236 vaccines in development with 40 of them being in some phase of the clinical testing already. So, let’s take a look at what COVID-19 vaccines are currently available.

Vaccine Efficacy
Moderna 94,1%
Pfizer and BioNTech 95%
AstraZeneca

62,1% in participants who received two standard doses;

90% in participants who received a low dose followed by a standard dose;

overall vaccine efficacy – 70,4%.

Sinovac

50.4% in late-stage trials in Brazil;

91.25% in Turkey;

65.3% in Indonesia.

Johnson & Johnson

85% in preventing severe disease,

72% in the US and 66% overall at preventing moderate to severe COVID-19

Sputnik V 92%
Novavax

89% in the UK,

49.4 – 60% in South Africa

Covaxin Phase 3 trial is not completed

 

Moderna

This American biotechnology company based in Cambridge develops vaccines based exclusively on messenger RNA (mRNA). It’s been working on the COVID-19 vaccine in cooperation with the National Institute of Allergy and Infectious Diseases (NIAID) since January. In March the scientists started human testing. The company got encouraged when, in summer, their prototype showed its efficiency on monkeys.

The vaccine contains genetic instructions for building a coronavirus protein, known as a spike. The immune system then is bound to respond and develop antibodies. Moderna’s prototype has one significant advantage over similar medical products. It could be stored at refrigerator temperatures for up to a month, while some other prospective candidates require ultra-cold storage containers.

The most recent update on Phase 3 of clinical trials is very promising. The impressive efficiency of 94.5% has prompted the company to seek Emergency Use Authorization (EUA) with the US FDA. However, the FDA members were previously hesitant to grant early approval to any candidate. They consider doing so could interfere with ongoing trials. Therefore, it’s still unknown when the vaccine can get to the general public.

Meanwhile, the company’s quick and effective response to the global collapse has triggered an increased interest of investors. The shares first went up in early spring as the vaccine started showing positive dynamics. After the latest press release, the stock price surged over 10%. Currently, it is over $98 per share, while the peak performance was $103. Compared to the last year, the stock price skyrocketed over 370% while the company’s market cap rose to $38.63B with robust investments from the US government.

Pfizer and BioNTech

A few days ago, American multinational pharmaceutical corporation Pfizer and German biotechnology company Biopharmaceutical New Technologies (BioNTech) announced that their mRNA-based COVID-19 vaccine candidate demonstrates 95% efficiency against COVID-19. Furthermore, the companies reached the safety milestone required by the US FDA for Emergency Use Authorization and are going to submit the data for approval in the US as well as report to other regulatory agencies around the world. Jointly, the producers can make up to 50 million doses in 2020 and 1.3 billion doses in 2021. US, Japan, Canada, and the EU have already made some deals with Pfizer/BioNTech development group for supplementation of at least 100 million doses.

Pfizer Inc. engages in the discovery, development, and manufacture of healthcare products while specializing in medicines, vaccines, and consumer healthcare. The good news about the COVID-19 prototype caused Pfizer’s share price to jump nearly 8% in mid-November. However, after the rush of enthusiasm, the stock price started to gradually fall. The news about the Moderna vaccine with almost the same efficacy but the much better logistic potential has undermined Pfizer’s unique status. Currently, its share price equals $36.6, almost the same as a year ago.

BioNTech, on the other hand, is showing positive share dynamics. The current $104.75 price is a 401.54% increase over 1 year. This German company develops pharmaceutical candidates based on messenger RNA (mRNA) for use as individualized cancer immunotherapies, vaccines against infectious diseases, protein replacement therapies for rare diseases, etc. It also engineered cell therapy, novel antibodies, and small molecule immunomodulators as treatment options for cancer. Combating the two most pressing healthcare issues of the modern world gives BioNTech an advantage over its closest rivals.

AstraZeneca

The multinational Swedish-British biopharmaceutical company has been among the world’s largest pharmaceutical companies since its merger in 1999. It offers a range of medical treatment products for oncology; cardiovascular, renal, and metabolism (CVRM) diseases; respiratory diseases, and immunology. AstraZeneca’s products also address neuroscience issues, some inflammatory diseases, and infections, particularly those resistant to current antibiotics. The company has previously worked with influenza vaccines.

Together with the University of Oxford, the European biopharmaceutical leader has started developing its experimental COVID-19 vaccine in April. The first results from Phase 3 trials may seem not as impressive as their counterparts mentioned before. Nevertheless, even at this rate, the candidate can save millions of lives. Moreover, if the initial test results confirm, it could prove to be more affordable since less than two doses are required. It also means that more people could be vaccinated without increasing the planned vaccine supply.

The total vaccine efficacy is 70%. The results comprise data from two dosing regimes. In the first dosing scenario, the volunteers had a full dose injected twice at a one-month interval. This proved effective only for 62%. The second variant involved a half-dose first and a full dose of the vaccine later. In the latter case, efficiency had a higher 90% rate. Both Pfizer’s and Moderna’s prototypes need two full doses to create a proper immune reaction.

AstraZeneca’s vaccine candidate also uses a different technology than Pfizer and Moderna do. Instead of mRNA, viral vector technology deploys an altered common cold virus to carry the genetic material of the coronavirus and produce an immune response.

As the company will seek an Emergency Use Listing from the World Health Organization to accelerated vaccine availability in low-income countries, investors are now pondering over its stock potential. AstraZeneca’s shares started increasing in late April when the vaccine collaboration was announced and reached a peak in mid-July when early human testing showed promising results. The stock has expectedly dropped in November after the impressive data releases from Pfizer and Moderna. Investors’ doubts about the new vaccine market competitiveness brought AstraZeneca’s stock rate to $55.30. During the last 5-day period, its performance has fallen by 1.76%. At the same time, the stock price has risen around 9% since the same period last year.

Sinovac

Sinovac Biotech Ltd. is a China-based biopharmaceutical company that focuses on the research, development, manufacture, and sales of vaccines for infectious diseases. Its COVID-19 vaccine is among the few that had already entered Phase 3 clinical trials. However, the results are available only for Phase 1/2. The firm stated it won’t be pressured by the recent Western reports and will release the relevant data only when it is assured to obtain enough number of qualified COVID-19 cases in its double-blind, placebo-controlled trials to certify vaccine effectiveness.

The speed of data acquisition depends on the severity of the epidemic situation in host countries (Brazil, Indonesia, and Turkey) and the enrollment schedule of volunteers in partnered institutions. For instance, in Brazil, the trials were temporarily suspended due to the death of a volunteer. They resumed as the death was proved unrelated to the vaccine use.

According to the officials, nearly 60,000 people had received a vaccine by early November. Although using more traditional methods than the US developments – a chemically inactivated version of the virus – the Chinese vaccine gives “quick” response in the trials. The Sinovac representatives state the vaccinated people are developing virus-fighting antibodies within 14 days of receiving a dose. This would make the vaccine suitable for emergency use.

Despite the vaccine positive feedback and global anticipation, trading of the company’s stock didn’t resume at Nasdaq. Nasdaq halted trading in Sinovac stock in February 2019 due to the corporate-governance battle within the company and never reopened it. Current US-Chinese tension can’t improve the company’s position, for sure. Nevertheless, Sinovac has received $15 million in funding from Advantech Capital and Vivo Capital to advance the development of its COVID-19 vaccine.

Johnson & Johnson

It appears that Johnson & Johnson is not only good at making the no-tears shampoo. The world’s largest healthcare producer has also made a shot at combating the virus that put on masks on the whole world population. In fact, the American pharmaceutical giant has already been working on potential vaccines for other infectious diseases such as HIV, Ebola, Hepatitis B, etc. Since the beginning of the pandemic outbreak, the company started using its previous experience to develop an investigational COVID-19 vaccine candidate.

The vaccine is made and tested by the Janssen Pharmaceutical Companies of Johnson & Johnson. The JNJ vaccine candidate is based on the virus’s genetic instructions for building the spike protein. Namely, the vaccine uses double-stranded DNA of a modified adenovirus that can enter cells but can’t replicate inside them or cause illness. After the vaccine shot, the adenoviruses bump into cells and latch onto proteins on their surface. The cell sends out warning signals to activate immune cells nearby. It causes the immune system to react more strongly to the spike proteins. Other immune cells may bump into the coronavirus spikes on the surface of vaccinated cells or free-floating spike protein fragments. Thus, the immune cells can lock onto the spike proteins. They need further activation by helper T cells to proliferate and pour out antibodies that target the spike protein.

Currently, adenovirus-based vaccines are used against a wide variety of pathogens, including tuberculosis and HIV. Adenoviruses are generally considered a suitable vector for delivering target antigens to mammalian hosts because of their capability to induce both innate and adaptive immune systems.

The JNJ vaccine will be injected in either a single-shot or two-dose regime. Both variants are currently being tested. The candidate is expected to be stable for two years at -20°C and for up to three months in the 2°C to 8°C range used to store many biological substances.

On December 17, 2020, Johnson & Johnson announced the full enrollment was reached in the large-scale, pivotal, multi-country Phase 3 trial (ENSEMBLE) of its single-dose vaccine candidate with approximately 45,000 participants. The initial plan was to conduct the trial with 60,000 volunteers. However, the research team decided to cap the recruitment early due to the fact that Covid-19 is so pervasive across the country. The more virus cases there are in the U.S., the more likely it is that participants will be exposed to it, meaning researchers will be able to reach conclusions based on a smaller trial.

The data about vaccine effectiveness is supposed to be available by the end of January 2021. If the vaccine will prove to be safe and effective, the Company expects to submit an Emergency Use Authorization application to the U.S. FDA and other health regulatory bodies across the globe in February. Johnson & Johnson had already signed the communiqué with 15 other life science companies, along with the Bill & Melinda Gates Foundation, to bring safe, effective, and affordable vaccines to lower-income countries on a not-for-profit basis for emergency pandemic use. The company plans to allocate up to 500 million vaccine doses at self-cost with delivery beginning mid next year.

The vaccine news supports the JNJ’s strong position on the stock market. Its shares plunged shortly this year but rose 4.8% in April after the drug and consumer products company reported first-quarter profit and sales that increased above expectations. The all-time high Johnson & Johnson stock closing price was $157.38 on December 31, 2020. It rose by 7.41% over a year.

Sputnik V

The vaccine long-approved by Russian authorities was registered for emergency use in August 2020 before Phase 3 of clinical trials. Post-registration clinical trials involving more than 40,000 people in Russia and Belarus launched on August 25. Its clinical trials have also been announced in the UAE, India, and Venezuela. In December, the mass vaccination using Sputnik V started. Doctors, teachers, and social workers are among the first candidates to get a two-dose vaccine. Yet, some journalist reports show the number of volunteers is quite small so far. According to Statista, only 3 out of 10 Russians would agree to participate in the free mass vaccination, while over 40% of respondents certainly did not want to receive the vaccine in the near future.

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The vaccine was patented by Gamaleya National Research Institute of Epidemiology and Microbiology. Being named after the first Soviet space satellite, the Russian vaccine is supposed to start a new era in fighting COVID-19. In its essence, Sputnik V is an adenoviral vector-based vaccine, similar to the one developed by Johnson & Johnson. The gene from adenovirus, which causes the infection, is removed.

At the same time, a gene carrying the code of the coronavirus spike protein is inserted. This inserted element then gets inside human cells. It is safe for the body but still helps the immune system to react and produce antibodies. However, unlike the JNJ candidate, the Russian vaccine comprises two entirely different injections – using different carriers for the coronavirus each time. That could make the vaccine more effective.

According to the developers, the Sputnik V vaccine’s efficacy is 91.4%, rising to 100% when used against severe cases of coronavirus. However, as the Phase 3 trials are still ongoing, many scientists across the globe are skeptical about the data accuracy and the rush to lead the vaccination records.

Though the vaccine has to be stored at -18C at least in its liquid form, in a dry form it can be stored at a temperature of +2 to +8 degrees Celsius. That makes it possible to transfer Sputnik V internationally. Thus, more than 1.2 billion doses of the vaccine were ordered by over 50 countries. In October 2020, Russia applied for prequalification of Sputnik V at the WHO to speed up its availability worldwide.

However, according to the BBC, this more practical, powder version of the vaccine is not yet being made in large amounts. Overall, the vaccine is currently produced on a much smaller scale than initially planned since the two shots are completely different. While the first component is more stable, producing the second one requires some strict temperature regulation and longer brewing time inside the bioreactors. The biotech firms working on the task need to resolve this issue before scaling up.

The Russian Direct Investment Fund (RDIF), which has been backing the vaccine and marketing it globally, reached an agreement with the Indian pharmaceutical company Hetero to produce more than 100 million Sputnik V doses per year in India. In Russia, a handful of private drug companies are entrusted with the production. Those include BIOCAD, a private-sector pharmaceutical company that hasn’t been involved in vaccine work before.

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None of the companies dealing with the Sputnik V vaccine is publicly traded, so we can’t say whether the involvement affected their market position somehow. The sole (100%) shareholder of RDIF is the Russian Federation represented by the Federal Agency for State Property Management (Rosimushchestvo).

Novavax

The new COVID-19 vaccine candidate is produced by the American biotech company Novavax with the help of their innovative proprietary recombinant nanoparticle vaccine technology. This protein-based vaccine involves the purified spike protein of the inactivated virus itself, produced and formulated as a nanoparticle structure. It also contains an ‘adjuvant’, a substance to help strengthen the immune responses to the vaccine. Once injected, it stimulates the immune system to start producing antibodies and induces T-cell immune responses. The Novavax candidate is stable and can be stored in a liquid form at 2°C to 8°C, allowing for successful cold chain management with existing infrastructure.

The official results of clinical trials differ for the two regions involved. While its efficacy against the recent virus mutation found in the UK was 89% at least seven days after individuals had received two doses of vaccine, in South Africa the vaccine efficacy was 60% in people living without HIV. For HIV patients, the efficacy was a little under 50%. Scientists believe the variant found in South Africa has an additional three or four mutations involving immunodominant components of the spike protein that could interfere with the vaccine-induced neutralizing activity of the virus. The vaccine is also currently being tested in the US and Mexico in clinical trials called PREVENT-19.

On February 3, 2021, EMA’s human medicines committee (CHMP) started a rolling review of the given vaccine needed to speed up the assessment of a promising medicine during a public health emergency.

Before the pandemic started, the Novavax shares were not highly valued. In 2019, the NVAX stocks fell from $46 to a mere $4. Since the company started developing a COVID-19 vaccine candidate, its shares skyrocketed by more than 2,700%. After the announced results, the company’s shares spiked up even further. While on January 28 Novavax stocks traded at about $130, on February 4 the price had already reached over $280. That brings the company’s market cap to 19.116B.

Covaxin

Covaxin is India’s first indigenous COVID-19 vaccine by Bharat Biotech developed in collaboration with the National Institute of Virology (NIV), which is a branch of the Indian Council of Medical Research (ICMR). The vaccine is developed using Whole-Virion Inactivated Vero Cell derived platform technology. Inactivated vaccines contain dead viruses, incapable of infecting people but still able to instruct the immune system to mount a defensive reaction against an infection.

At the beginning of the year 2021, India’s drug regulator gave emergency approval to this government-backed vaccine, before the completion of trials. The vaccine has undergone only the Phases 1 and 2 studies, with a total of 755 subjects enrolled. Therefore, it’s too early to speak about safe mass vaccination. So far, the candidate is approved only for restricted use, in clinical trial mode. Unsurprisingly, the rush has caused heated debate in the medical community about the political implications of such an approval. According to the Lancet publication, the outcomes for national vaccination levels may be significant.

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The company already faced some difficulties in finding the necessary number of volunteers for the phase 3 trials. Hence, the recruitment finished a week later than expected. Nevertheless, it didn’t hinder Bharat Biotech to sign a new agreement with Ocugen Inc to co-develop, supply, and commercialize Covaxin for the US market.

As of now, Bharat Biotech is not listed on any stock exchanges, although the media suggested it had been mulling an IPO since 2017. The company is funded by 3 investors, raising a total of $14.1M in funding over 3 rounds.

Vaccine Side effects
Moderna

Mild or moderate injection-site side effects (pain, redness, swelling, etc) are observed in more than 84% of patients following both doses. Delayed reactions (erythema, induration, and tenderness) occurred in 0.8% of patients following the first dose and 0.2% of patients following the second dose. 

Adverse events related to the vaccine were reported in 8.2%. The most were fatigue (1.5%) and headache (1.4%). Serious adverse events occurred in 0.6% in both vaccine and placebo groups. Two deaths that occurred in the vaccine group were not directly linked to vaccination (one from cardiopulmonary arrest and one by suicide). 

Pfizer and BioNTech

As of December 23, 2020, reports of 4,393 (0.2%) adverse events after receipt of the vaccine were submitted to the Vaccine Adverse Event Reporting System (VAERS). Among these, 175 case reports were identified for further review as possible cases of a severe allergic reaction, including anaphylaxis.

During clinical trials, 84% of recipients had typical injection site reactions, 63% reported fatigue, while headache and muscle pain affected about 55% and 38%, respectively. 

Current reports do not suggest any unexpected increase in fatalities in frail, elderly individuals or any unusual characteristics of adverse events following vaccination.

AstraZeneca The most frequently reported adverse reactions were injection site tenderness (>60%); injection site pain, headache, fatigue (>50%); myalgia, malaise (>40%); pyrexia, chills (>30%); and arthralgia, nausea (>20%). By day 7 the incidence of subjects with at least one local or systemic reaction was 4% and 13% respectively.
Sinovac Side effects include fatigue, fever, redness, and pain, with mostly mild symptoms. In Phase 1 trials, adverse reactions for the days 0 and 14 cohort were reported by 7-9 people (29% – 38%). For the days 0 and 28 cohort, side effects were observed in 3-4 people (13% – 17%). In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40-42 (33% – 35%), and for the days 0 and 28 cohort, the result was 23 (19%). 
Johnson & Johnson Overall fever rates were 9% and Grade 3 fever 0.2%. Overall serious adverse events (SAEs) reported were higher in participants who received placebo as compared to the active vaccine candidate. No anaphylaxis was observed.
Sputnik V The most commonly reported side effects were flu-like symptoms, pain at the injection site and fatigue. Serious side effects were rare and four deaths were reported in the study, although none were considered to be the result of the vaccine. Most reported adverse events were grade 1 (7485 [94%] of 7966 total events). 45 (0.3%) of 16 427 participants in the vaccine group had serious adverse events; none were considered associated with vaccination, with confirmation from the independent data monitoring committee.
Novavax In early trials, 80% of recipients reported side effects at the site of injection, including pain and tenderness. More than 60% had other side effects, mostly headaches, muscle pain, and fatigue. Most reactions were mild or moderate. 8 patients had severe side effects, though none required hospitalisation. Newer data isn’t available yet, but Novavax states that severe, serious, and medically attended adverse events occurred at low levels and were balanced between vaccine and placebo groups.
Covaxin Side effects include injection site pain, swelling, redness, itching, stiffness in the upper arm, weakness in the injection arm, body ache, headache, fever, malaise, weakness, rashes, nausea, and vomiting. There is also a “remote chance” that Covaxin could cause severe allergic reactions such as difficulty in breathing, swelling of the face and throat, a fast heartbeat, rash all over the body, dizziness and weakness. The exact percentage is unknown yet. The company promised to pay compensation to recipients in case of any serious adverse effects experienced after receiving the antidote. 

Besides, we’ve prepared some calculations and facts helping to determine if you should buy shares of the pharmaceutical companies.

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