Status of the Top 5 vaccines candidates
Avertim has a vast experience in the pharmaceutical and especially the vaccines industry. Therefore, we are closely watching the development of COVID-19 candidates and working with some of the leading companies to plan activities such as manufacture ramp-ups. In this article, find out more about the latest development of the most advanced vaccine projects, often lead by partnerships of leading pharmaceutical development and manufacturing companies.
Over 230 vaccines
The WHO tracks the global research efforts against COVID-19 and continuously reports on their progress. As of November 2020, there are more than 230 vaccines against COVID-19 in different stages of pre-clinical and clinical development (see Figure 1 or read our previous article). Scientists and companies are currently testing 63 vaccines in clinical trials (Phase I, II and III) and altough some vaccines have received emergency use authorization, no vaccine was fully approved yet.
Figure 1: Number of currently developed vaccines worldwide
Mid-December, it became apparent that during the cyber-attack on the EMA, COVID-19 vaccine documents from Pfizer and Moderna were breached. In the meantime, a new faster spreading coronavirus strain surfaced in the U.K but also in South Africa, a new coronavirus strain has been observed. While the U.K. variant will most likely not alter the effectiveness of the current vaccines, there is a chance that the South-African variant will. Moreover, the South-African variant appears to evade prior immunity which makes the patients‘ own antibodies but also antibody therapies less effective.
> October: Regeneron geneticists announced that they have linked 4 gene locations and 3 specific genes to the level of COVID susceptibility and severity of the symptoms. This is taking a step forward in unravelling and beating COVID since it could aid in predicting which people are more likely to be infected and more likely to experience severe symptoms.
> November: an important month in the battle against Covid since both Pfizer and Moderna have shown data of >90% efficacy of their vaccine candidate, spreading the hope that a vaccine might be on the market by end-year. At the end of November, the US federal government began distributing Regeneron’s antibody therapy starting with 30,000 dosages after FDA approval. Unlike the vaccines, aiming to prevent COVID-19, the Regeneron antibody cocktail can be used as a therapy to treat COVID-patients.
> December: Interpol warned that organized criminal networks might target the COVID-19 vaccine shipments. Moreover, with vaccine candidates coming close to an actual roll-out, complementary materials or supplies required are gearing up for a busy month ahead. Becton Dickinson is investing $1.2 billion in a new production site to keep up with the demand for prefilled syringes. Due to the promising data of Pfizer and Moderna and its upcoming FDA review, it is realistic that before year-end, 20 million Americans will be vaccinated, achieving the White house’s goal. The goal of researchers in California is to develop a CRISPR-based COVID-19 test detecting positive test with smartphones in under 30min. The currently used PCR-based tests take significantly longer. On December 7th, the first at-home test kit by Quest Diagnostics was approved by the FDA. The kit can detect SARS-CoV-2 as well as the common flu virus, Influenza A and B, allowing patients to seek appropriate care. On the 9th of December, the European Medicines Agency declared that it was hit by a cyberattack. So far, it is unclear who orchestrated the attack and if any data was compromised.
#1 BioNTech-Pfizer-Fosun Pharma
With BNT162 RNA Vaccines
The most advanced vaccine projects worldwide in clinical development.The German biotechnology company BioNTech is working in cooperation with Pfizer and Fosun Pharma on developing its RNA vaccines BNT162, which entered a combined phase I/II clinical trial in early May and is currently in a phase II/III trial.
WHAT HAPPENED LATELY?
On Monday, December 14th, vaccinations were kicked off in the US, using the Pfizer shot. Meanwhile, the World Health Organization discussed with Pfizer to include its vaccine in the COVAX program. As part of an agreement with China’s Shanghai Fosun, BioNTech will supply 100 million vaccine doses to China. On Monday 21st of December, the Pfizer and BioNTech vaccine received conditional marketing authorization from the European Medicines Agency. On December 27th, Germany started their vaccination campaign. Meanwhile, the German Health Minister is looking into ways to stretch the vaccine supply by splitting vaccine vials into six instead of the standard 5 doses. Other governments are looking to stretch the vaccine supply by delaying the second dose. The EMA now confirmed that a second vaccination within 42 days, instead of the initially listed 21 days, is covered with the authorization.
At the start of January, Belgium is only set to receive half of the doses of the Pfizer vaccine that it ordered due to technical issues in December. On Tuesday, 5th of January, Belgium started their vaccination campaign. Beginning of January, it was reported that Germans are feeling frustrated by the slow roll-out of the vaccination campaign. During the first two weeks of their vaccination spree, Germany managed to vaccinate 533,000 people, which is only 2/3 of the doses that were received. A study showed that the Pfizer vaccine seems effective against a key mutation in the novel strains of coronavirus found in the U.K. and South Africa.
BioNTech announced that they are aiming to boost vaccine supplies by introducing a new six-dose vial instead of the standard five-dose vial. Next to that it is looking to expand to new sites.
> September : Mid-September, BioNTech agreed to buy a biologics facility from Novartis in Germany and is expecting it to be fully operational in the first half of 2021. With the new site in Marburg, BioNTech is eyeing an annual capacity of up to 750 million doses. End of September, Pfizer announced that it expects conclusive data from its phase 3 vaccine trial by the end of October. However, a group of 60 leading researchers and bioethicists requested at least 2 months’ worth of safety data after administration of the second dose before seeking FDA authorisation. Honouring this request would push emergency approval into late November.
> October : at the beginning of October, CNBC reported that two participants in the Pfizer late-stage clinical trial encountered unpleasant side-effects like high fever, headache, body aches and chills. The participants however declared that they think the side effects are worth the protection against the coronavirus. On October 6th, Allele Biotechnology pressed patent charges against Pfizer and BioNTech for using an allele-made fluorescent protein during the development of the vaccine. The claim is currently under review by the European Medicines agency (EMA). Mid October, Pfizer and BioNTech closed a deal to supply Taiwan with 30 million doses and New Zealand with 1.5 million doses of their mRNA-based COVID-19 vaccine, BNT162. The earliest delivery is expected by the first quarter of 2021. On October 13th, Pfizer got approval from the FDA to include younger participants, age 12-15, in its COVID trials. Pfizer expanded its phase 3 trial with 14,000 additional participants with the aim to increase diversity in the testing group. In the trial, participants with stable chronic infections like hepatitis B and C as well as HIV are included.
On October 16th, Pfizer CEO Albert Bourla said that Pfizer will not file for EUA until at least the third week of November, contradicting earlier statements that it would win approval before the US presidential election of November 3rd. After gathering preliminary data on the working of the vaccine, the company stated that it wants to collect additional manufacturing and safety data.
On October 19th, Pfizers production site in Puurs, Belgium kicked off the production of hundreds of thousands of vaccines. The vaccines are already produced to be ready to ship when the FDA gives US approval in November. End of October, Analysts predicted that the Pfizer vaccine could initially take 50% of the market and drop to around 25% once the vaccines from Johnson & Johnson, Moderna, AstraZeneca, Sanofi and others are approved for commercialization.
End of October, the UK’s drug regulating authorities has accelerated the review of the Pfizer vaccine as they gear up to approve as soon as possible.
> November: at the start of November, Pfizer declared that it has developed new infrastructure to facilitate the transport of its cold-storage vaccine, including a temperature-tracked thermal cooler. On November 9th, Pfizer allowed an early peek into their phase 3 trial data and results are promising with 90% efficacy in preventing COVID-19.
By mid-November, Pfizer and BioNTech closed a multibillion-dollar deal to supply the EU with 200 to 300 million vaccine doses. The most important manufacturing sites to supply Europe will be the BioNTech site in Germany and Pfizer’s production site in Puurs, Belgium. Since the European Union agreed to pay €15.50 per vaccine dosage, the deal is worth €3.1 to €4.65 Billion, depending on the order size. According to Health Secretary Alex Azar, the US government plans to start vaccinating nursing home residents, healthcare workers and first responders in December if Pfizer submits its data as soon as expected. Since the promising data was released for the Pfizer vaccine, concerns were raised about the required ultracold storage. As a reaction, Pfizer is considering a second-generation vaccine formula, like a powder form. Fosun, the exclusive rights holder to the Pfizer and BioNTech’s vaccine in the Greater China region has located a storage facility near the Hong Kong airport which could serve as a large ultracold storage area for the vaccine.
On November 19th, Pfizer CEO Albert Bourla has declared that with results of 95% efficacy, Pfizer obtained the required safety data to file for emergency use authorization. Pfizer's and BioNTech's vaccine could potentially get approval in the UK by the end of November or beginning of December. The delivery of the vaccine could begin hours after the authorization and the first injection could even start from the 7th of December. In the US, Pfizer and BioNTech could roll out its vaccine shortly after the 10th of December, merely within 24 hours of FDA authorization. It is expected that by mid-December, Pfizer supplies the US with 6.4 million of 40 million doses.
> December: beginning of December, Pfizer and BioNTech have submitted its vaccine candidate for conditional market approval to the European Medicines Agency (EMA). In reaction, the EMA declared that it plans to announce the decision on the Pfizer vaccine on December 29th. On the 2nd of December, the UK Medicines & Healthcare Products Regulatory Agency has granted emergency use authorization to the Pfizer and BioNTech vaccine only 10 days after it began its review of the trial data. This seemingly hasty decision is strongly critiqued by the European Union.
On the 4th of December, Pfizer filed for emergency use approval in India. Following in the UK’s footsteps, Bahrein approves the Pfizer vaccine. Tuesday 8th of December was baptised as V-day in the UK, starting the vaccination of the public with the Pfizer-BioNTech shot, employing healthcare workers and tens of thousands of volunteers. The New York Times reports that the goal is to vaccinate 20,000 citizens over the course of the coming months.The following day, Canada became the third country to approve the Pfizer vaccine candidate for early usage. Prime minister Justin Trudeau declared that Canada has secured an early delivery of 249,000 dosages, expected to arrive by year-end. Vaccinations are expected to start mid-December. The Chief Scientist at The World Health Organization (WHO) announced that it could offer a decision on the Pfizer vaccine within a couple of weeks. In the meantime, it may also review the Moderna and AstraZeneca vaccine. WHO authorization would be an important milestone since it could potentially allow vaccines to be used in countries that had not yet started the review. On December 12th, the FDA approved the Pfizer vaccine for emergency use authorization in the United States, being the fourth country to approve the vaccine. Celebrating the win, Pfizer is already looking into the future and plans to file for full FDA approval by April 2021.
#2 AstraZeneca-Oxford University
WHAT HAPPENED LATELY?
On December 30th, the U.K. approved the AstraZeneca vaccine for emergency use. Following the UK, on January 3rd, India and Mexico approved the AstraZeneca vaccine for emergency use. Meanwhile, South Korea has kicked off the review of the AstraZeneca vaccine with plans to rollout its vaccination campaign in February
> September: at the end of September, the AstraZeneca phase 3 trial remained on hold in the US while the FDA investigates the patient illness that initiated the hold. Since then, the AstraZeneca trial already resumed in the UK, Brazil, South Africa, Japan, and India. Meanwhile, the European Union governments agreed to help cover liability costs if AstraZeneca’s vaccine candidate triggers unexpected side effects after FDA authorization. To supply poorer countries, including India, AstraZeneca also partnered with the Serum Institute of India (SII) to produce up to 200 million vaccine doses.
> October: at the beginning of October, AstraZeneca and the University of Oxford stated that they are hopeful to get approval for high-risk patients in the UK by the end of December 2020. On October 21st, a participant of the AstraZeneca phase 3 clinical trial passed away. The patient who died was participating in the Brazilian trial and received the control treatment, not the COVID-19 vaccine according to the Federal University of Sao Paulo. Since, Reuters reported that there are no concerns about the safety of the trials, the study will continue. On October 23rd, the FDA wrapped up its investigation into the AstraZeneca vaccine and gave the go to resume its phase 3 US trial. End of October, similarly to Pfizer, the UK’s drug regulating authorities has accelerated the review of the AstraZeneca vaccine.
> November: at the beginning of November, AstraZeneca announced a delay in its vaccine supply to the UK. Britain will not receive the planned 30 million but rather 4 million doses. In the meantime, AstraZeneca closed a deal with Argentina to supply 22 million vaccine doses starting in 2021. The Serum Institute of India has already manufactured up to 40 million AstraZeneca vaccine doses to meet the demand once the vaccine is authorized. On November 23rd, AstraZeneca announced that on average, their vaccine candidate has an efficacy of 70%. However, doubts are raised concerning the early read-out from the trial data because the reported 70% efficacy was calculated including the results of two groups on two different dosing regimens: the first regimen (n = 2,741) of a half dose followed by a full dose led to a 90% efficacy while the second regimen (n=8,895) of two full doses showed 62% efficacy.
AstraZeneca admitted that the administration of the half-dose followed by a full dose was a mistake and was given to a smaller number of trial participants, casting doubt on the actual efficacy of the AstraZeneca vaccine candidate. After receiving the promising efficacy data, COVAX closed a deal with AstraZeneca for the supply of hundreds of millions of vaccine doses. Meanwhile, AstraZeneca announced that they have the capacity and resources to produce 200 million vaccine doses by year-end and 700 million doses by Q1 of 2021. An important edge that the AstraZeneca has over Pfizer or Moderna is that its vaccine candidate can be stored and transported at normal refrigerator temperatures for a minimum of six months.
> December: At the start of December, it was announced that the data from the AstraZeneca US trial will be shared by late January to the FDA since the early read-out of trial data from the UK and Brazil was doubted. On Monday, 7th of December, AstraZeneca files for emergency use authorization of its vaccine to the Serum Institute of India. Meanwhile, AstraZeneca closed a deal with Halix, a Dutch contract manufacturing organization, to enable large-scale commercial manufacturing. Halix will perform the activities from its facilities at the Leiden Bio Science Park in the Netherlands. AstraZeneca is planning a new trial by the end of December, combining its own vaccine candidate with the Russian Sputnik V vaccine in the hope it will boost the vaccine efficacy.
WHAT HAPPENED LATELY?
Mid December, the US government has snatched an additional 100 million doses of the Moderna shot. On December 18th, the Moderna vaccine was approved by the FDA for emergency use in the US. The European Commission acted on its option to purchase an additional 80 million vaccine doses. A fraction of people with facial fillers experienced facial swelling as a side effect of the Moderna vaccine.
On January 4th, after the US and Canada, Israel became the third country to approve the Moderna vaccine. On the 6th of January, the EMA approved the Moderna vaccine for emergency use. Two days later, the U.K. authorized Moderna’s vaccine as the third shot in the fight against the pandemic.
> September : at the end of September, Canada placed an order for 20 million doses of the Moderna RNA-based vaccine. Moderna is hopeful after seeing a triggered immune response at both dose levels in the phase 1 data.
> October: on October 1st, Moderna CEO Stéphane Bancel declared that Moderna will not have enough safety data on its vaccine to seek EUA from the FDA before the end of November. At the earliest, it is expected to file for full approval by late January. In the first weeks of October, similarly to Pfizer, three of the Moderna phase 3 clinical trial participants have faced side effects like high fever, head and body aches and chills. End of October, Moderna announced that it is optimistic and on track to report the phase 3 trial data by the end of November.
> November: mid-November, Swiss drug regulator Swissmedic started the rolling review of the Moderna vaccine, allowing review of data of the ongoing trials as soon as it is available. On November 16th, Moderna declared its promising late-stage clinical data, upstaging the Pfizer success story. Their mRNA vaccine candidate showed nearly 95% efficacy while no significant side effects were observed. Moderna said it will use this data to file for emergency use authorization in the coming weeks, treading in Pfizer's footsteps. Moreover, new stability testing revealed that the Moderna vaccine should remain stable at temperatures as cold as your standard fridge for 30 days and up to six months when stored at a standard freezer temperature. Moderna announced that it will submit its vaccine for emergency use authorization by end-November with an FDA review scheduled on the 17th of December. On November 24th, the European Union closed a deal with Moderna to secure up to 160 million doses of its vaccine candidate. On November 30th, Moderna announced that they filed for emergency use authorization. One day after filing for EUA in the US, the European Medicine Agency received Moderna‘s application for conditional marketing. The decision is scheduled for January 12th.
> December: beginning of December updated phase 1/2 trial data raised the hopes for the durability of the immunity after the COVID-19 vaccine since antibody levels stayed elevated in the 90 days after a second dose. On the 10th of December, Moderna dosed the first teen participants in their phase 2/3 trial to evaluate the efficacy in this age group, hoping to provide data by spring 2021.
#4 Johnson & Johnson
With its Ad26.COV2.S vaccine
Johnson & Johnson is developing vaccines using viral vector technology and clinical testing is currently in a combined phase I/II trial launched in July.
WHAT HAPPENED LATELY?
At the end of December, Johnson & Johnson declared that it had wrapped up enrollment for its late stage trial and is expecting to release data by the end of January and seek approval around February. Johnson & Johnson is on track to receive U.K. approval within weeks.
> September: on September 21st, Johnson & Johnson kicked off its phase 3 trial with the goal of 60,000 participants for its viral-vector based vaccine. By September 28th it was reported that, the vaccine triggered an immune response in healthy patients on just one dose.
> October: at the beginning of October, Johnson & Johnson partnered with Grand River Aseptic Manufacturing for fill-finish work for up to 100 million doses. Meanwhile, they entered another vaccine supply agreement, entailing 200 million doses of its vaccine with the option of 200 million additional doses, when approved by regulators. On October 13rd, bad news hit Johnson & Johnson when the trial is put on hold after a participant suffers from an unexplained illness. End of October and beginning of November, the J&J Covid-19 clinical trials resumed in the US as well as in Brazil.
> November: at the start of November, J&J announced that they closed a preliminary deal with Aspen Pharmacare, Africa’s largest drug manufacturer, to produce the J&J vaccine in South Africa, boosting capacity with 300 Million doses per year. Mid-November, next to the current late-stage trial for the J&J one-dose vaccine, a phase 3 trial was started for their two-dose vaccine.
> December: on December 1st, the EMA started a rolling review of Johnson & Johnson vaccine candidate, similarly to the AstraZeneca, Moderna and Pfizer/ BioNTech vaccine candidates. On December 9th, it was announced that due to rising cases of COVID-19 in the US Johnson & Johnson decided to decrease the number of volunteers for its phase III trial from 60,000 to 40,000. The vaccine trial is expected to be completed in January and could be followed by filing for emergency use authorization to the FDA in February.
With their SARS-CoV-2 vaccine candidates
Sanofi is working on recombinant protein vaccines in combination with adjuvants developed by GSK to stimulate the immune system.
WHAT HAPPENED LATELY?
There are no new updates regarding the search for a vaccine from GSK and Sanofi.
> September: in September, GSK-Sanofi started the Phase I/II trial for their recombinant protein, in combination with adjuvants, vaccine candidates. Now that the vaccine started testing on humans, the companies are optimistic and aiming for approval of the vaccine in early 2021. End of September, a deal was struck with Canada to provide up to 72 million doses of the vaccine for January 2021.
> October: end of October, an agreement was made to supply the COVAX Alliance with 200 million doses. Intermediary data from the Sanofi and GSK phase I/II showed that its vaccine caused an immune response in the age group of 18-49 years but failed to trigger a similar response in the older groups. This weak data forces Sanofi and GSK to delay its vaccine to end of 2021.