Pipeline Report 2021: COVID-19 Edition
As the world awaits the production and distribution of hundreds of millions of doses of COVID-19 vaccines that have been granted emergency use authorization, biopharmaceutical companies and manufacturers are developing the next wave of vaccines and therapeutics to combat the pandemic.
By Andrew Humphreys • [email protected]
Hundreds of vaccines and therapeutics are being studied and developed by companies, research institutes, universities and others targeting coronavirus disease 2019. This report reviews some of the leading troops on the front lines in the global fight against COVID-19.
The Pfizer–BioNTech COVID-19 Vaccine was the first to be authorized for use in the United States under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older. The companies plan to submit a Biologics License Application (BLA) with the U.S. FDA for a possible full regulatory approval during 2021. Under Operation Warp Speed, the Department of Defense (DoD) in partnership with agencies within the Department of Health and Human Services (HHS), including the U.S. Centers for Disease Control and Prevention (CDC), are managing U.S. allocation and distribution of the vaccine through a July 2020 agreement.
BNT162b2 was the code name during development and testing, tozinameran is the proposed international nonproprietary name (INN), and Comirnaty is the brand name.
“Pfizer’s purpose is breakthroughs that change patients’ lives, and in our 171-year history there has never been a more urgent need for a breakthrough than today with hundreds of thousands of people continuing to suffer from COVID-19,” stated Pfizer Chairman and CEO Albert Bourla on Dec. 11.
“We founded BioNTech to develop new technologies and medicines that utilize the full potential of the immune system to fight serious diseases,” said BioNTech CEO and Co-founder Ugur Sahin, M.D., on the same historic date. “Today we are another step closer to our vision. We believe that today’s Emergency Use Authorization, and the subsequent distribution of our vaccine that has demonstrated an efficacy rate of 95 percent and a favorable safety profile, will help to save lives across the United States and could accelerate a return to normality.”
The FDA based the regulatory agency’s decision on the totality of scientific evidence shared by the companies, including data from a pivotal Phase III clinical trial announced during November and published during December in The New England Journal of Medicine. The Phase III data showed a vaccine efficacy rate of 95 percent in participants without previous SARS-CoV-2 infection (first primary objective) and additionally in participants with and without prior SARS-CoV-2 infection (second primary objective), in each case measured from seven days after the second dose. The Data Monitoring Committee for the clinical trial has not reported any serious safety concerns related to the vaccine. Efficacy was consistent throughout age, gender, race, and ethnicity demographics. All study participants continue to be monitored to evaluate long-term protection and safety for an additional two years after their second dose.
In vitro studies demonstrate the Pfizer and BioNTech COVID-19 vaccine elicits antibodies that neutralize SARS-CoV-2 with key mutations present in the U.K. and South African variants, as reported by the companies on Jan. 27. The sera neutralized SARS-CoV-2 with key mutations present in the United Kingdom and South Africa variants, as measured by studies performed by Pfizer and the University of Texas Medical Branch (UTMB). The results were published on the preprint server for biology, bioRxiv, and submitted to a peer-reviewed journal.
Pfizer and BioNTech are encouraged by their early in vitro study findings and are assessing the full set of mutations in the spike protein of the South African variant. While these findings do not indicate the necessity for a new vaccine to address the emerging variants, Pfizer and BioNTech are prepared to respond if a variant of SARS-CoV-2 shows evidence of escaping immunity by the COVID-19 vaccine. Pfizer and BioNTech will continue to monitor emerging SAR-CoV-2 strains and continue to conduct clinical trials to monitor the vaccine’s real-world effectiveness. The companies believe that the flexibility of BioNTech’s proprietary mRNA vaccine platform is well suited to develop new vaccine variants if necessary.
Pfizer and BioNTech announced a joint-development and distribution collaboration (excluding China) on March 17, 2020, intended to accelerate development of BioNTech’s potential first-in-class COVID-19 mRNA vaccine program, BNT162. The rapid advancement of this collaboration builds on the R&D collaboration into which Pfizer and BioNTech entered during 2018 to develop mRNA-based vaccines for the prevention of influenza. BioNTech and Fosun Pharma are jointly developing BNT162 in China.
Based in Germany, Biopharmaceutical New Technologies (BioNTech) is a next-generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. The company’s broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bi-specific checkpoint immuno-modulators, targeted cancer antibodies and small molecules.
BioNTech has teamed up with Pfizer, one of the world’s leading biopharmaceutical companies, for a joint program known as “Project Lightspeed.” The program initially started with four vaccine candidates from BioNTech’s COVID-19-focused project, each representing different mRNA formats and target antigens. Two of the four vaccine candidates include a nucleoside modified mRNA (modRNA), one includes a uridine containing mRNA (uRNA), and the fourth vaccine candidate uses self-amplifying mRNA (saRNA). Each of the mRNA formats is combined with a lipid nanoparticle (LNP) formulation. The larger spike sequence is included in two of the vaccine candidates, and the smaller optimized receptor binding domain (RBD) from the spike protein is included in the other candidates. The RBD-based candidates contain the piece of the spike that is believed to be most significant for eliciting antibodies that can inactivate the virus.
BioNTech and Pfizer added a fifth vaccine candidate against COVID-19 falling under the partners’ BNT162 program. Using modRNA like the EUA-issued BNT162b2, the fifth vaccine candidate was expected to enter a Phase I/II study in September 2020, according to reports.
With a team of 1,000 people, Moderna impressively went from a novel virus sequence to a COVID-19 vaccine with 94 percent efficacy and an Emergency Use Authorization (EUA) in 11 months. Moderna COVID-19 Vaccine (mRNA-1273) received an EUA from the FDA on Dec. 18, 2020, and the company started supplying to the government shortly thereafter. Moderna’s vaccine has been authorized for emergency use by the FDA for active immunization to prevent coronavirus disease 2019 caused by SARS-CoV-2 in individuals 18 years of age and older.
A biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, Moderna will continue to leverage a U.S.-based manufacturing infrastructure to supply the COVID-19 vaccine to the U.S. government. As of Jan. 27, the U.S. government had agreed to purchase 200 million doses of the Moderna COVID-19 Vaccine, with discussion of a potential deal that would bring the U.S. government’s confirmed order commitment to 300 million doses.
The Moderna COVID-19 vaccine has demonstrated activity against emerging strains of SARS-CoV-2, as reported by the company on Jan. 25. Vaccination with the Moderna COVID-19 Vaccine produced neutralizing titers against all key emerging variants tested, including B.1.1.7 and B.1.351, first identified in the United Kingdom and Republic of South Africa, respectively. The study demonstrated no significant impact on neutralizing titers against the B.1.1.7 variant relative to prior variants. A six-fold reduction in neutralizing titers was evident with the B.1.351 variant relative to prior variants. Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are anticipated to be protective. This clinical trial was conducted in collaboration with the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The manuscript was submitted as a preprint to bioRxiv and was to be filed for peer-reviewed publication.
First detected during September 2020 in the United Kingdom, the SARS-CoV-2 B.1.1.7 variant has 17 mutations in the viral genome with eight mutations located in the spike (S) protein. The B.1.351 variant, first detected in South Africa, has 10 mutations located in the spike (S) protein. Each variant has spread at a rapid rate and is associated with increased transmission and a higher viral burden after infection.
“As we seek to defeat the COVID-19 virus, which has created a worldwide pandemic, we believe it is imperative to be proactive as the virus evolves,” stated Moderna CEO Stéphane Bancel. “We are encouraged by these new data, which reinforce our confidence that the Moderna COVID-19 Vaccine should be protective against these newly detected variants. Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective to boost titers against this and potentially future variants.”
In 10 years and with more than $3 billion in investments since inception, Moderna has transformed from a science research-stage company advancing programs in the promising-but-still-unproven field of mRNA, to an enterprise with its first medicine having treated millions of people, a diverse clinical portfolio of vaccines and therapeutics across six modalities, a broad intellectual property portfolio in areas such as mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for clinical and commercial production at scale and at unprecedented speed.
Moderna’s mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. The company has 24 development programs underway across these therapeutic areas, with 13 programs having entered the clinic. Moderna has been named a top biopharma employer by Science for the past six years.
London-based AstraZeneca’s COVID-19 vaccine was the third to be granted a conditional marketing authorization (CMA) in the European Union. On Jan. 29, the vaccine was cleared for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based the positive opinion on data from a rolling review of study data from the primary analysis of the Phase III program led by the University of Oxford. The vaccine was previously approved for use in the United Kingdom at the end of December. AstraZeneca is working with the European Union following the approval of a CMA for active immunization to begin across member states.
There was some doubt regarding the possible EU authorization of AstraZeneca’s vaccine after Germany’s vaccine committee said on Jan. 28 it was recommending that the vaccine should only be offered to people aged between 18-64 years. The following day, when the AstraZeneca CMA was announced, the EMA said there were not yet enough results in older participants (over 55 years old) to provide a figure for how well the vaccine will work in this group. However, the EMA reportedly said that “protection is expected, given that an immune response is seen in this age group and based on experience with other vaccines.”
According to AstraZeneca CEO Pascal Soriot, “Today’s approval underscores the value of AstraZeneca’s COVID-19 vaccine, which is not only effective and well tolerated, but also easy to administer and, importantly, protects fully against severe disease and hospitalizations. We are deeply grateful to Oxford University, participants in the clinical trials and AstraZeneca colleagues for their unwavering commitment to providing this lifesaving vaccine to millions of Europeans.”
AstraZeneca continues to work with regulatory authorities around the globe to support the ongoing rolling reviews for emergency supply or conditional approval during the health crisis. AstraZeneca is additionally seeking Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries.
COVID-19 Vaccine AstraZeneca (formerly AZD1222) was co-invented by the University of Oxford and its spin-out company Vaccitech. The vaccine uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the virus if it later infects the body.
CHMP’s recommendation was based on an analysis of 23,745 participants aged 18 years and older, accruing 232 symptomatic COVID-19 infections from the UK and Brazil Phase III studies performed by Oxford University.
The safety data published as of late January encompasses more than 20,000 participants enrolled across four clinical trials in the UK, Brazil and South Africa. The publication in The Lancet confirmed that COVID-19 Vaccine AstraZeneca was well tolerated and that there were no confirmed serious safety events. The participants represented diverse ethnic and geographic groups who were healthy or had stable underlying medical conditions.
In addition to the program led by Oxford University, AstraZeneca is carrying out a large study in the United States and worldwide. Oxford University and AstraZeneca expect to enroll up to 60,000 participants globally. As of Feb. 5, AstraZeneca expected results from the U.S. clinical study by March.
The AstraZeneca COVID-19 vaccine has been granted a CMA or emergency use in nearly 40 countries as of late January, spanning four continents including in the EU, various Latin American countries, India, Morocco, and the UK.
As this magazine went to press, Britain launched a trial on Feb. 4 to evaluate the immune responses generated if doses of the COVID-19 vaccines from Pfizer and AstraZeneca are combined in a two-shot regimen. Initial data on immune responses is anticipated to be generated around June 2021.
Human trials of a coronavirus vaccine combining Russia’s Sputnik V vaccine with that developed by Britain’s AstraZeneca and Oxford University were anticipated to begin during early February. AstraZeneca initially announced plans to explore the possibility of working with Russian scientists on a joint vaccine in December. Russia’s sovereign wealth fund RDIF and the Gamaleya Institute on Nov. 23 offered AstraZeneca to use one of the two components of the Sputnik V vaccine in AstraZeneca’s clinical studies.
The trials are taking place in Azerbaijan, Argentina, Saudi Arabia, the UAE, Belarus, Russia and elsewhere, according to R-Pharm Chairman Alexey Repik via a Reuters report. The Russian drug manufacturer R-Pharm will produce the Sputnik V and AstraZeneca shots.
Combining the vaccines is expected to boost the efficacy of the AstraZeneca shot. The average efficacy rate was 70.4 percent in interim late-stage data, versus more than 91.4 percent in trials of Sputnik V, which prompted Russian vaccine developers to suggest an effort to combine the two, Reuters reported. Each vaccine employs two doses, an initial shot and a booster, and they are based on a similar scientific approach using common cold viruses as vectors.
An estimated 100 participants are expected in the Phase I/II studies, first receiving the AstraZeneca shot and then the Sputnik V vaccine 29 days later.
Gamaleya National Center
As the world’s first COVID-19 vaccine registered by Russia on Aug. 11, Sputnik V was developed by the Gamaleya Research Institute and produced in cooperation with the Russian Direct Investment Fund (RDIF). Sputnik V is based on a well-studied human adenoviral vector-based platform. The ongoing Sputnik V post-registration clinical study in Russia involves 40,000 volunteers.
Also known as Gam-COVID-Vac, Sputnik V is one of the most effective vaccines globally, with efficacy confirmed at more than 91 percent based on data analysis of the final control point of clinical studies. Sputnik V efficacy against severe cases of coronavirus is 100 percent.
A peer-reviewed study published in The Lancet on Feb. 2 confirmed 91.6 percent efficacy in protecting against symptomatic COVID-19, on par with vaccine data from Western Hemisphere players. The Phase III data encompasses nearly 20,000 patients across numerous hospitals and clinics in Russia participating in the two-dose scheme. The study additionally analyzed people older than 60 years based on 2,144 participants, demonstrating Sputnik V to be 91.8 percent effective.
Sputnik V is among the safest vaccines in the world due to its unique technology combining two different human adenoviral vectors. This process provides for a stronger and longer-term immune response compared to vaccines using the same component for both inoculations.
The regimen with two different adenoviral vectors for a prime and a boost immunization is a unique and ground-breaking discovery of scientists from the Gamaleya Center. This helps to completely avoid immunity to the first vector, which forms after the first inoculation and thus to raise efficacy and create long-term immunity, according to the scientists. Among the leading COVID-19 vaccines, Sputnik V is the first to use the two-vector technology.
RDIF is ramping up the production of Sputnik V jointly with partners and manufacturers. As a two-dose vaccine, the cost of one dose for international markets is less than $10. The lyophilized (dry) form of Sputnik V can be stored at a temperature of +2 to +8 degrees Celsius.
Requests for more than 1.2 billion vaccine doses have come from more than 50 countries. Sputnik V supplies for the worldwide market will be produced by RDIF’s international partners in India, Brazil, China, South Korea and other countries.
Sputnik V is named after the first Soviet space satellite. The launch of Sputnik-1 in 1957 reinvigorated space research around the globe, creating a so-called “Sputnik moment” for the worldwide community.
Gilead’s Veklury (remdesivir) became the first U.S. FDA-approved treatment for COVID-19 on Oct. 22, 2020. Veklury was approved by the FDA for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. Veklury was previously authorized by FDA for emergency use to treat COVID-19.
The October U.S. marketing clearance is based on three randomized controlled studies including the final results of the NIAID double blind, placebo-controlled Phase III ACTT-1 trial. The clinical study demonstrated that treatment with Veklury resulted in clinically meaningful improvements across multiple outcome assessments versus placebo in hospitalized patients with COVID-19. Based on the strength of these data, Veklury has become a standard of care for treating COVID-19 in hospitalized patients, according to Gilead.
As an antiviral medicine, Veklury works to stop replication of SARS-CoV-2. In the randomized, double-blind, placebo-controlled ACTT-1 study, Veklury shortened the time to recovery by five days in hospitalized COVID-19 patients. The ACTT-1 study results are complemented by data from two Phase III open-label trials (SIMPLE-Severe and SIMPLE-Moderate) of Veklury conducted in adults with severe and moderate COVID-19.
In parallel with the FDA approval, the U.S. regulatory agency additionally issued an EUA for the use of Veklury to treat hospitalized pediatric patients under 12 years of age weighing at least 3.5 kg or hospitalized pediatric patients weighing 3.5 kg to less than 40 kg with suspected or laboratory confirmed COVID-19 for whom use of an intravenous (IV) agent is clinically appropriate.
The nucleotide analog Veklury is invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury has broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, SARS, Marburg, MERS, and SARS-CoV-2.
Veklury has been approved or authorized for temporary use as a COVID-19 treatment in at least 50 countries. The medicine is widely available in hospitals throughout the United States, following early investments to rapidly expand manufacturing capacity to increase supply.
In January 2021, Gilead increased the company’s total product sales guidance range to $24.30 billion to $24.35 billion, reflecting increased Veklury sales as hospitalization and treatment rates were higher than expected due to another COVID-19 surge.
Johnson & Johnson
J&J is on track to become the first company to receive EUA for a one-shot COVID-19 vaccine, with a submission to U.S. health authorities announced on Feb. 4 as this magazine was going to press, with an application to European authorities reportedly weeks away. The FDA scheduled a meeting of the regulatory agency’s Vaccines and Related Biological Products Advisory Committee on Feb. 26 to discuss the company’s request for emergency use authorization. The Pfizer/BioNTech and Moderna vaccines were authorized by the FDA one day after such a meeting.
On Jan. 29, the company released topline efficacy and safety data from the Phase III ENSEMBLE clinical study. Data showed that the investigational single-dose COVID-19 vaccine JNJ-78436735 in development at Janssen Pharmaceutical Companies met all primary and key secondary endpoints. The topline safety and efficacy data are reportedly based on 43,783 participants accruing 468 symptomatic cases of COVID-19.
The Phase III ENSEMBLE trial is designed to assess the efficacy and safety of the Janssen COVID-19 vaccine candidate in protecting moderate to severe COVID-19, with co-primary endpoints of 14 days and 28 days post-vaccination. Among all participants from different geographies and including those infected with an emerging viral variant, Janssen’s COVID-19 vaccine was 66 percent effective overall in preventing moderate to severe COVID-19, 28 days after vaccination. The onset of protection was observed as early as day 14, according to Janssen. The level of protection against moderate to severe COVID-19 infection was 72 percent in the United States, 66 percent in Latin America and 57 percent in South Africa, 28 days following vaccination.
The vaccine was 85 percent effective in preventing severe disease across all regions studied, 28 days after vaccination in all adults 18 years of age and older. Efficacy against severe disease increased over time with no cases in vaccinated participants reported after 49 days.
Janssen’s COVID-19 vaccine candidate showed complete protection against COVID-related hospitalization and death, 28 days after vaccination. The company said there was a clear effect of the vaccine on COVID-19 cases requiring medical intervention (hospitalization, ICU admission, mechanical ventilation, extracorporeal membrane oxygenation), with no reported cases among participants who had received the Janssen COVID-19 vaccine, 28 days after vaccination.
“Johnson & Johnson embarked on the global effort to combat the COVID-19 pandemic a year ago, and has brought the full force of our capabilities, as well as tremendous public-private partnerships, to enable the development of a single-shot vaccine,” stated J&J Chairman and CEO Alex Gorsky. “Our goal all along has been to create a simple, effective solution for the largest number of people possible, and to have maximum impact to help end the pandemic. We’re proud to have reached this critical milestone and our commitment to address this global health crisis continues with urgency for everyone, everywhere.”
The ENSEMBLE program was initiated in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of HHS under Other Transaction Agreement HHSO100201700018C, and the NIAID.
A separate Phase III study of the investigational Janssen COVID-19 vaccine candidate to explore a two-dose regimen (ENSEMBLE 2) is under way. ENSEMBLE 2 is a complementary, planned, pivotal, large-scale, multi-country trial evaluating the safety and efficacy of a two-dose regimen of the investigational Janssen vaccine candidate for the prevention of COVID-19 in up to 30,000 participants around the globe. The ENSEMBLE and ENSEMBLE 2 trials are being carried out in parallel.
“Johnson & Johnson was built for times like these – and from day one, we have kept science, transparency and collaboration at the center of all our efforts to fight this deadly pandemic,” according to Gorsky.
One week after reporting positive Phase III vaccine data, Maryland-based Novavax on Feb. 4 announced the start of the rolling review process for authorization of NVX-CoV2373 in the United States, United Kingdom and Canada. To date, Novavax has begun the rolling review process with the EMA, U.S. FDA, U.K. Medicines and Healthcare products Regulatory Agency, and Health Canada. The reviews will continue while Novavax completes pivotal Phase 3 studies in the U.K. and U.S. and through initial authorization for emergency use granted under country-specific regulations.
Novavax announced on Jan. 28 that the protein-based COVID-19 vaccine candidate NVX-CoV2373 met the primary endpoint, with a vaccine efficacy of 89.3 percent, in the company’s Phase III study conducted in the United Kingdom. The clinical trial assessed efficacy during a period with high transmission and with a new UK variant strain of the virus emerging and circulating widely. The study was conducted in partnership with the UK Government’s Vaccines Taskforce. Novavax additionally reported successful results of a Phase IIb study performed in South Africa.
The study enrolled more than 15,000 participants between 18-84 years, including 27 percent older than 65. The primary endpoint of the UK Phase III study is based on the first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least seven days after the second study vaccination in serologically negative (to SARS-CoV-2) participants at baseline.
“With today’s results from our UK Phase III and South Africa Phase IIb clinical trials, we have now reported data on our COVID-19 vaccine from Phase I, II, and III trials involving over 20,000 participants. In addition, our PREVENT-19 US and Mexico clinical trial has randomized over 16,000 participants toward our enrollment goal of 30,000. NVX-CoV2373 is the first vaccine to demonstrate not only high clinical efficacy against COVID-19 but also significant clinical efficacy against both the rapidly emerging UK and South Africa variants,” said Novavax President and CEO Stanley C. Erck.
According to Clive Dix, Chair, UK Vaccine Taskforce, “These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine. The efficacy shown against the emerging variants is also extremely encouraging. This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus.”
In the South Africa Phase IIb trial, 60 percent efficacy for the prevention of mild, moderate and severe COVID-19 disease was observed in the 94 percent of the study population that was HIV-negative. The study achieved the primary efficacy endpoint in the overall trial population, including HIV-positive and HIV-negative subjects (efficacy of 49.4 percent).
This study enrolled more than 4,400 patients starting in August 2020, with COVID-19 cases counted from September through mid-January. During this period, the triple mutant variant – which contains three critical mutations in the receptor binding domain (RBD) and multiple mutations outside the RBD – was widely circulating in South Africa. Preliminary sequencing data is available for 27 of 44 COVID-19 events, with 92.6 percent (25 out of 27 cases) the South Africa escape variant.
“The 60 percent reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the first COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,” stated Professor Shabir Maddi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax COVID-19 vaccine trial in South Africa. “I am encouraged to see that Novavax plans to immediately begin clinical development on a vaccine specifically targeted to the variant, which together with the current vaccine is likely to form the cornerstone of the fight against COVID-19.”
At the end of 2020, Novavax announced the initiation of the PREVENT-19 late-stage trial in the U.S. and Mexico to test the efficacy, safety and immunogenicity of NVX-CoV2373. The clinical study builds on research from Phase I/II trials showing that the vaccine provoked a robust immune response, generated highly neutralizing antibodies against the virus and was generally well-tolerated.
NVX-CoV2373 consists of a full-length, prefusion spike protein made using Novavax’ recombinant nanoparticle technology and the company’s proprietary saponin-based Matrix-M adjuvant. A purified protein encoded by the genetic sequence of the SARS-CoV-2 spike (S) protein that is produced in insect cells, it can neither cause COVID-19 nor can it replicate. The purified protein is stable at 2°C to 8°C and is shipped in a ready-to-use liquid formulation that enables distribution using standard vaccine supply chain channels.
PREVENT-19 (the PRE-fusion protein subunit Vaccine Efficacy Novavax Trial | COVID-19) is a randomized, placebo-controlled, observer-blinded study to assess the efficacy, safety and immunogenicity of NVX-CoV2373 with Matrix-M in up to 30,000 subjects 18 years of age and older versus placebo. The trial design has been harmonized to align with other Phase III studies conducted under the auspices of Operation Warp Speed, including the use of a single external independent Data and Safety Monitoring Board to test safety and conduct an unblinded review when predetermined interim analysis events are reached.
The clinical trial’s primary endpoint is the prevention of PCR-confirmed, symptomatic COVID-19. The study’s key secondary endpoint is the prevention of PCR-confirmed, symptomatic moderate or severe COVID-19. Both endpoints will be assessed at least seven days after the second trial vaccination in volunteers who have not been previously infected with SARS-CoV-2.
The company intended to recruit, enroll and study a diverse population with an emphasis on communities and demographic groups most impacted by the disease as well as to maximize participation of older adults and those living with co-morbid conditions (e.g., obesity, hypertension and diabetes) that place them at higher risk of COVID-19 complications.
Preclinical studies demonstrated that NVX-CoV2373 induced antibodies that block binding of spike protein to cellular receptors and provided protection from infection and disease. The protein-based vaccine candidate was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera in Phase I/II clinical testing.
PREVENT-19 is being carried out with support from Operation Warp Speed partners, including the Department of Defense and NIAID, and the Biomedical Advanced Research and Development Authority. BARDA is additionally providing up to $1.6 billion under a DoD deal.
GlaxoSmithKline and Vir Biotechnology entered a collaboration in April 2020 to find coronavirus solutions, including SARS-CoV-2. The collaboration is using Vir’s proprietary monoclonal antibody platform technology to accelerate existing and identify new antiviral antibodies that could be used as therapeutic or preventative options to help address the COVID-19 pandemic and future outbreaks. The companies are leveraging GlaxoSmithKline’s expertise in functional genomics and combining their capabilities in CRISPR screening and artificial intelligence to identify anti-coronavirus compounds that target cellular host genes. GSK and Vir are additionally applying their combined expertise to research SARS-CoV-2 and other coronavirus vaccines.
The initial focus of the collaboration has been to accelerate the development of specific antibody candidates identified by the Vir platform, VIR-7831 and VIR-7832, that have shown high affinity for the SARS-CoV-2 spike protein and are highly potent in neutralizing SARS-CoV-2 in live virus-cellular assays.
Vir Biotechnology and GlaxoSmithKline announced on Dec. 17 that the first patient had been dosed in a new sub-trial of the National Institutes of Health’s Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Program Phase III study. The clincial trial is designed to test the safety and efficacy of VIR-7831 for treating hospitalized adults with COVID-19. Also known as GSK4182136, VIR-7831 is a fully human anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) investigational monoclonal antibody that was selected based on the drug’s potential to neutralize the virus, kill infected cells, provide a high barrier to resistance and achieve high concentrations in the lungs (one of the major sites of infection).
ACTIV-3 is one of several studies in the NIH’s ACTIV program, an NIH led public-private partnership set up to accelerate development of the most promising treatments and vaccine candidates for COVID-19. ACTIV-3 has been designed as a “master protocol” that allows for the simultaneous evaluation of multiple investigational therapeutics as they become available, but within the same clinical trial structure, across multiple study sites.
VIR-7831 is additionally being studies in the global Phase II/III COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) trial for the early treatment of COVID-19 in adults at high risk of hospitalization. The Phase III part of the COMET-ICE study is evaluating the safety and efficacy of a single intravenous (IV) infusion of VIR-7831 or placebo in 1,300 non-hospitalized participants around the world. The primary efficacy endpoint is the proportion of adult patients who have progression of COVID-19 as defined by the need for hospitalization or death within 29 days of randomization. The COMET clinical development program for VIR-7831 additionally includes a planned Phase III study for the prevention of symptomatic infection.
VIR-7831/GSK4182136 is a monoclonal antibody for which preclinical data suggest the drug’s ability to neutralize SARS-CoV-2 live virus in vitro and in vivo. The antibody binds to an epitope on SARS-CoV-2 shared with SARS-CoV-1, indicating that the epitope is highly conserved, which may make it more difficult for resistance to develop. VIR-7831 has been engineered with the potential to enhance lung bioavailability and have an extended half-life.
Dr. Hal Barron, chief scientific officer and president of R&D, GlaxoSmithKline, stated: “With new infection and hospitalization rates reaching record highs, the world needs multiple options to help combat this pandemic. We are developing solutions to fight this virus, from prevention through treatment, to provide relief from COVID-related illness. Our treatment option, VIR-7831, which has a high barrier to resistance and has the potential to neutralize the virus and kill infected cells, could allow this treatment to be effective for patients in hospital settings, where other antibodies have so far not shown an impact.”
GlaxoSmithKline is collaborating with several organizations working on promising COVID-19 vaccines by providing access to the company’s adjuvant technology. In a collaboration with Sanofi that brings together two of the world’s largest vaccine companies, GlaxoSmithKline is developing an adjuvanted recombinant protein-based COVID-19 vaccine candidate with a Phase IIb trial anticipated to start during February 2021. The use of an adjuvant is of particular significance in a pandemic situation since it may reduce the amount of vaccine protein necessary per dose, allowing more vaccine doses to be produced and therefore contributing to protecting more people.
Vir is concentrated on combining immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. The clinical-stage immunology company has assembled four technology platforms that are designed to stimulate and enhance the immune system by exploiting critical observations of natural immune processes. Vir’s development pipeline is composed of product candidates targeting hepatitis B virus, influenza A, SARS-CoV-2, human immunodeficiency virus and tuberculosis.
Vir and GSK took on a collaboration partner as announced on Jan. 27, marking the first time that monoclonal antibodies from separate companies would be brought together to explore potential outcomes. Eli Lilly, Vir, and GlaxoSmithKline formed a collaboration to assess a combination of two COVID-19 therapies in low-risk patients with mild to moderate COVID-19. Lilly expanded the company’s BLAZE-4 study to evaluate the administration of bamlanivimab (LY-CoV555) 700mg with VIR-7831 500mg, two neutralizing antibodies that bind to different epitopes of the SARS-CoV-2 spike protein.
As a neutralizing antibody directed against the spike protein of SARS-CoV-2, bamlanivimab is designed to block viral attachment and entry into human cells, thus neutralizing the virus. Bamlanivimab is authorized for emergency use for treating mild to moderate COVID-19 in patients who are at high risk for progressing to severe COVID-19 and/or hospitalization.
“We believe that VIR-7831 has significant potential as a single agent, and we are optimistic about the pending interim data from two Phase III trials evaluating its potential for early treatment and in hospitalized patients,” according to George Scangos, Ph.D., Vir’s chief executive officer. “As the virus continues to evolve, we, along with Lilly and GSK, share the view that we should pursue all possibilities to help end the pandemic and maximize the number of lives that can be saved. This trial is a first step to assess whether the administration of VIR-7831, with its high barrier to resistance and potent effector function, alongside bamlanivimab, which has strong outcomes data in early treatment, can provide potential benefits beyond monotherapy.”
“Bamlanivimab is a potent antibody – with data from multiple Phase II and III clinical trials, which have demonstrated robust evidence for both treating and preventing COVID-19,” noted Daniel Skovronsky, M.D., Ph.D., Lilly’s chief scientific officer and president of Lilly Research Laboratories. “With a virus like SARS-CoV-2, it’s expected that variants could emerge that require new therapeutic options, which is why Lilly is studying bamlanivimab together with other neutralizing antibodies, including etesevimab. Adding VIR-7831 to our study is an important part of our commitment to develop therapies to treat current and future strains of COVID-19 until vaccines are widely available and utilized.”
Lilly’s bamlanivimab 700 mg injection is authorized for use under EUA for treating mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.
Bamlanivimab was granted Emergency Use Authorization by the U.S. FDA based on interim data from the Phase II BLAZE-1 study, which was published in The New England Journal of Medicine. These data show the therapy may help patients clear the virus and reduce COVID-19-related hospitalizations when administered early in the disease course.
The safety and efficacy of bamlanivimab is being studied with other neutralizing antibodies to provide a possible safeguard against potential viral resistance. The recombinant, neutralizing human IgG1 monoclonal antibody (mAb) bamlanivimab emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after its discovery by AbCellera and the scientists at the NIAID Vaccine Research Center. Bamlanivimab was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.
Lilly has successfully completed a Phase I trial of bamlanivimab in hospitalized patients with COVID-19 (NCT04411628). A Phase II/III trial in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501) is underway. A Phase III study of bamlanivimab for the prevention of COVID-19 in residents and staff at long-term care facilities (BLAZE-2, NCT04497987) is also continuing. Additionally, bamlanivimab is being evaluated in the National Institutes of Health-led ACTIV-2 study in ambulatory COVID-19 patients.
The U.S. government committed to purchase 1,450,000 doses of bamlanivimab as of late January, which includes 950,000 doses already delivered and a deal to deliver 500,000 additional doses by March 31, 2021.
Bamlanivimab 2800 mg and etesevimab 2800 mg together significantly reduced COVID-19-related hospitalizations and deaths in high-risk patients recently diagnosed with COVID-19, meeting the primary endpoint of the Phase III BLAZE-1 study, Lilly reported on Jan. 26. Etesevimab (LY-CoV016, additionally known as JS016) is a recombinant, fully human monoclonal neutralizing antibody that specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can block the binding of the virus to the ACE2 host cell surface receptor. According to Lilly, point mutations were introduced into the native human IgG1 antibody to mitigate effector function. The company licensed etesevimab from Junshi Biosciences after the drug compound was jointly developed by Junshi and the Institute of Microbiology, Chinese Academy of Science (IMCAS). Junshi Biosciences leads development in Greater China, and Lilly heads development efforts in the rest of the world.
Lilly has successfully completed a Phase I trial (NCT04441931) of etesevimab in healthy U.S. volunteers to test safety, tolerability, pharmacokinetics, and immunogenicity. The company is conducting a Phase II/III trial in people recently diagnosed with COVID-19 in the ambulatory setting (BLAZE-1, NCT04427501). Junshi Biosciences has completed a similar Phase I study in healthy volunteers in China and has initiated Phase Ib/II studies in COVID-19 patients around the world.
Another Lilly treatment received COVID-19 authorization from U.S. health regulators on Nov. 19. FDA granted Emergency Use Authorization for baricitinib to be used in combination with Gilead’s remdesivir in hospitalized adult and pediatric patients 2 years of age or older with suspected or laboratory-confirmed COVID-19 who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
The oral JAK inhibitor baricitinib was discovered by Incyte and licensed to Lilly. The medicine is approved and commercially marketed as Olumiant in the United States and more than 70 countries for treating adults with moderate to severe rheumatoid arthritis. Olumiant is approved in the European Union for the treatment of adults with moderate to severe atopic dermatitis who are candidates for systemic therapy.
Sanofi is collaborating with GlaxoSmithKline on a COVID-19 vaccine candidate using the same recombinant protein-based manufacturing technology as one of Sanofi’s seasonal influenza vaccines, combined with GSK’s established pandemic adjuvant platform. Phase I/II trial results of the vaccine candidate demonstrated an immune response comparable to patients who recovered from COVID-19 in adults aged 18 to 49 years, but a low immune response in older adults likely due to an insufficient concentration of the antigen, according to the company.
Sanofi and GlaxoSmithKline intended to begin a new Phase II study during February 2021 with support from BARDA, part of the HHS Office of ASPR, that will evaluate the vaccine candidate with an improved antigen formulation to achieve high-level immune response across all age groups. If data are positive, a global Phase III trial could start during Q2 2021. Positive results from this study would lead to regulatory filings in second-half 2021, with potential availability of doses in the fourth quarter of 2021.
Sanofi is also developing a messenger RNA vaccine in partnership with Translate Bio. Preclinical data demonstrated that two immunizations of the mRNA vaccine induced high neutralizing antibody levels comparable to the upper range of those observed in infected humans. Sanofi anticipates the Phase I/II study to start during first-quarter 2021.
In late January 2021, a deal was struck through which Sanofi will support manufacturing and supply of BioNTech’s COVID-19 vaccine being jointly developed with Pfizer. Sanofi will provide BioNTech access to the company’s established infrastructure and expertise to produce more than 125 million doses of COVID-19 vaccine in Europe. Initial supplies will originate from Sanofi’s production sites in Frankfurt from the summer of 2021.
Merck & Co.
Merck announced on Jan. 25 the discontinued development of both of the company’s SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591. Merck planned to continue focus on the company’s SARS-CoV-2/COVID-19 research strategy and production capabilities on advancing two therapeutic candidates, MK-4482 and MK-7110. According to management, this decision follows Merck’s review of findings from Phase I clinical studies for the vaccines. In these studies, V590 and V591 were generally well tolerated, but the immune responses were inferior to those evident following natural infection and those reported for other SARS-CoV-2/COVID-19 vaccines. Merck continues to advance clinical programs and to scale-up manufacturing for the investigational medicines MK-7110 and MK-4482 (molnupiravir).
In addition to advancing the development and production of MK-7110 and MK-4482, Merck continues to carry out SARS-CoV-2/COVID-19 research. Merck additionally continues to assess the potential of the measles-virus vector and vesicular stomatitis virus vector-based platforms and pursue broader pandemic-response capabilities. “The COVID-19 pandemic underscores the need for our company and our industry to continue to invest in research to address threats to health security,” Merck management stated.
Formerly known as CD24Fc, MK-7110 is a potentially first-in-class investigational recombinant fusion protein that modulates the inflammatory response to SARS-CoV-2, principally by targeting a novel immune pathway checkpoint. Interim results from a Phase III trial demonstrated a greater than 50 percent reduction in the risk of death or respiratory failure in patients hospitalized with moderate to severe COVID-19. Full results from this study were expected during first-quarter 2021. In December, Merck announced a supply dealt with the U.S. government to advance the manufacturing and initial distribution of MK-7110.
The oral novel investigational antiviral agent molnupiravir (MK-4482) is being developed in collaboration with Ridgeback Bio. Molnupiravir is being tested in Phase II/III studies in the hospital and out-patient settings. The primary completion date for the Phase II/III trials is May 2021. Merck anticipates initial efficacy data in the first quarter of 2021, which the company intends to share publicly if clinically meaningful.
Clover is developing an S-Trimer COVID-19 vaccine candidate using the clinical-stage biotechnology company’s proprietary Trimer-Tag technology. Clover’s S-Trimer is a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate. Similar to other enveloped RNA viruses including HIV, RSV, and influenza, SARS-CoV-2 is also an RNA virus that has a trimeric spike (S) protein on its viral envelope. The trimeric S protein of SARS-CoV-2 is responsible for binding to host cell surface receptor ACE2 and subsequent viral entry, making it the primary target antigen for vaccine development, according to Clover. S-Trimer resembles the native trimeric viral spike protein and is produced via a rapid mammalian cell-culture based expression system, and is intended to be adjuvanted.
Clover and biopharmaceutical company Dynavax Technologies on Feb. 1 unveiled a plan to initiate a global Phase II/III efficacy study with the S-Trimer COVID-19 vaccine candidate adjuvanted with CpG 1018 plus alum during first-half 2021. An interim analysis for vaccine efficacy is expected potentially in the middle of 2021. The Coalition for Epidemic Preparedness Innovations (CEPI) will continue to support the development of Clover’s COVID-19 vaccine candidate and is funding development, including the Phase II/III study, through licensure.
CpG 1018 is the adjuvant used in Heplisav-B [Hepatitis B Vaccine (Recombinant), Adjuvanted], an adult hepatitis B vaccine approved by FDA. Dynavax developed CpG 1018 to provide an increased vaccine immune response, which has been shown in Heplisav-B. According to the company, CpG 1018 provides a well-developed technology and a significant safety database, to support the rapid development and large-scale manufacturing of a COVID-19 vaccine. Upon completion of ongoing scale-up activities, the existing equipment capacity for CpG 1018 will amount to 600 million to 1.2 billion adjuvant doses yearly, depending on the final dose selected.
In a Phase I trial, Clover’s protein-based COVID-19 S-Trimer vaccine candidates in combination with adjuvants from either Dynavax or GlaxoSmithKline both performed well and induced high levels of neutralizing antibodies while showing favorable safety and tolerability profiles. Clover management anticipates that the company will produce hundreds of millions of vaccine doses during 2021 and up to 1 billion vaccine doses in peak annual production as required by worldwide demand.
“We believe this vaccine candidate could be efficacious while potentially having a differentiated, beneficial reactogenicity and safety profile which could make it attractive for a broad population of peoples,” said Clover CEO Joshua Liang.
Also on Feb. 1, Clover and GlaxoSmithKline announced the decision to discontinue their partnership to evaluate the S-Trimer COVID-19 vaccine candidate with GSK’s pandemic adjuvant system.
Inovio is developing INO-4800 as a DNA vaccine candidate against SARS-CoV-2. Inovio was the first company to initiate a Phase IIa study for INO-4700, a DNA vaccine candidate for a related coronavirus that causes MERS.
Comprising an optimized DNA plasmid, INO-4800 is delivered directly into cells in the body through a proprietary smart device to produce a robust, safe and tolerable immune response. INO-4800 is the first nucleic-acid based vaccine that is stable at room temperature for more than a year, at 37o C for more than a month, has a five-year projected shelf life at normal refrigeration temperature and does not need to be frozen during transport or storage – all of which are significant considerations when preparing for mass immunizations.
Inovio is conducting a Phase II/III clinical study for INO-4800 in the United States, called INNOVATE (INOVIO INO-4800 Vaccine Trial for Efficacy). The company announced in December the start of dosing subjects in the Phase II segment of INNOVATE. The Phase II segment of the study is designed to assess safety, tolerability and immunogenicity of INO-4800 in a two-dose regimen (1.0 mg or 2.0 mg), in a three-to-one randomization (in a planned total of 400 subjects) to receive either INO-4800 or placebo, to confirm the more appropriate dosing level for each of three age groups (18-50 years, 51-64 years and 65 years and older) for the subsequent Phase III efficacy evaluation. The INNOVATE study is funded by the U.S. DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in coordination with the Office of the Assistant Secretary of Defense for Health Affairs (OASD (HA)) and the Defense Health Agency (DHA).
Inovio has assembled a worldwide coalition of collaborators, partners and funders to rapidly advance the development of INO-4800. CEPI, the Bill & Melinda Gates Foundation, and the U.S. DoD have contributed significant funding to the advancement and manufacturing of the COVID-19 vaccine candidate. R&D collaborators include The Wistar Institute, the University of Pennsylvania, the University of Texas, Fudan University, and Laval University.
CureVac began development of the company’s mRNA-based COVID-19 vaccine candidate CVnCoV during January 2020. CVnCoV is an optimized, non-chemically modified mRNA, encoding the prefusion stabilized full-length spike protein of the SARS-CoV-2 virus, and formulated within Lipid Nano Particles (LNPs). Phase I and IIa studies of the vaccine started during June and September 2020, respectively.
Phase I interim data reported during November 2020 demonstrated that CVnCoV was generally well tolerated across all tested doses and induced strong antibody responses in addition to first indication of T cell activation. The quality of immune response was comparable to recovered COVID-19 patients, closely mimicking the immune response after natural COVID-19 infection, according to CureVac. The data supported the company’s decision to advance a 12µg dose into the pivotal Phase IIb/III trial, the HERALD study, which began in December 2020. Clinical study material is provided by CureVac’s substantial production capacities for mRNA vaccines at the company’s headquarters in Tübingen, Germany supported by the expansion of manufacturing capacities in Europe, enabling broad-scale manufacturing of CVnCoV for potential commercial supply preparedness.
CureVac and Bayer joined forces during January 2021 in a collaboration and services agreement. Bayer agreed to support CureVac in numerous areas, including the development, supply and key territory operations of CVnCoV. Bayer is contributing the company’s expertise and established infrastructure in fields such as clinical operations, regulatory affairs, pharmacovigilance, medical information, supply chain performance as well as support in selected countries.
CureVac will be the Marketing Authorization Holder for the vaccine, and Bayer will support CureVac with country operations within the European Union and additional markets. Bayer holds additional options to become Marketing Authorization Holder in other markets outside of Europe. The companies intend to combine their strengths for CureVac to be in a position to supply hundreds of millions of CVnCoV doses around the globe, once approvals are granted.
CureVac and GlaxoSmithKline announced a new collaboration on Feb. 3, building on the companies’ existing relationship, to jointly develop next-generation mRNA vaccines for COVID-19 with the potential for a multi-valent approach to address multiple emerging variants in one vaccine. GSK is also supporting the manufacture of up to 100 million doses of CVnCoV during 2021. The development program started immediately, with the target of introducing the vaccine in 2022.
Valneva SA’s VLA2001 is the only inactivated vaccine candidate in clinical trials against COVID-19 in Europe. The Phase I/II trial was reported as fully enrolled as of Jan. 28 and initial results are expected to be reported during April 2021. A total of 150 healthy adults aged 18 to 55 years have been recruited for the Phase I/II study, which started during mid-December 2020.
A specialty vaccine company focused on the prevention of infectious diseases with significant unmet medical need, Valneva announced in January advanced discussions with the European Commission (EC) for the supply of up to 60 million doses of VLA2001. During September 2020, Valneva announced a major COVID-19 vaccine partnership with the UK government for the supply of up to 190 million doses of VLA2001. Under this partnership pact, if vaccine development is successful, Valneva will provide the UK government with 100 million doses in second-half 2021 after an additional order of 40 million doses was announced on Feb. 1. Britain could still order another 90 million doses between 2023 and 2025, according to the French drugmaker.
VLA2001 is composed of inactivated whole virus particles of SARS-CoV-2 with high S-protein density, in combination with two adjuvants, alum and CpG 1018. This adjuvant combination has consistently induced higher antibody levels in preclinical experiments than alum-only formulations and demonstrated a shift of the immune response towards Th1. VLA2001 is produced on the company’s established Vero-cell platform, leveraging the manufacturing technology for Valneva’s licensed Japanese encephalitis vaccine Ixiaro. The process includes inactivation with BPL to preserve the native structure of the S-protein. CpG 1018 is a component of the FDA-approved Heplisav-B vaccine and received a positive opinion from the EMA’s CHMP on Dec. 10, 2020. Valneva expects VLA2001 to conform with standard cold chain requirements (2 degrees to 8 degrees Celsius).
Sinopharm’s COVID-19 vaccine was the first to be approved by China for general public use. The COVID-19 shot was developed by an affiliate of the state-backed pharma giant Sinopharm. The inactivated COVID-19 vaccine developed by Beijing Institute of Biological Products of Sinopharm CNBG was granted conditional registration by the NMPA of China on Dec. 30, 2020.
More than 60,000 volunteers of 125 nationalities have participated in the Phase III study of Sinopharm CNBG in countries outside China. According to company, the vaccine’s efficacy rate based on interim analysis is higher than the target set at the beginning, and its safety and effectiveness performances exceed the standard level of both the World Health Organization for market approval and the Chinese regulatory authority for conditional market approval, which entitles the vaccine a general public use in China.
“Generally speaking, Sinopharm CNBG’s COVID-19 vaccine has shown comprehensive strengths,” company management said. “A large sample of injection and data prove its safety and effectiveness. Besides, the vaccine doesn’t require freezing temperatures for storage, making transport and distribution much easier for most of the countries in the world. Its capacity is also large enough for massive inoculation.
Five countries have authorized emergency use for the Sinopharm vaccine as of mid-January 2021: China, the UAE, Bahrain, Egypt, and Jordan. More than 50 countries have expressed a willingness to procure the vaccine.
CanSino’s Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (“Ad5-nCoV”) became the first of its kind to enter clinical development during March 2020. Ad5-nCoV is also the first candidate with positive Phase I and II trial results published in the Lancet during May and July. The data has shown that a single-dose injection of the candidate can induce a balanced humoral and cellular immune response. In August, Ad5-nCoV became the first COVID-19 vaccine candidate in China to receive a patent. Ad5-nCoV is jointly developed by the Beijing Institute of Biotechnology (BIB), part of the Academy of Military Medical Sciences.
CanSino reported on Feb. 1, 2021, that the COVID-19 vaccine met its pre-specified primary safety and efficacy criteria at interim analysis, with no serious adverse events. The Phase III study saw more than 40,000 volunteers administered with the vaccine in 78 clinical trial sites across five countries in three continents. With these findings by the Independent Data Monitoring Committee (IDMC), CanSino can proceed with advancing the Phase III study for the candidate, which is also known as Convidecia.
CanSino initiated the late-stage trial for the one-dose vaccine in Russia in September in partnership with NPO Petrovax Pharm and struck a supply pact with Mexico.
Another China-based biopharma company at the forefront of the fight against COVID-19 through vaccine development is Sinovac. The Beijing-based company’s COVID-19 vaccine, CoronaVac, is being evaluated in Phase III clinical studies in Brazil, Indonesia, Turkey, and Chile.
In China, Phase I/II studies were conducted with results demonstrating the vaccine candidate can induce neutralizing antibodies among more than 90 percent of volunteers who received two doses of vaccination in adults and the elderly. The results of Sinovac’s Phase I/II trial on healthy adults aged 18-59 years old were published on Lancet Infectious Diseases on Nov. 17, 2020.
Sinovac anticipates to be able to manufacture 300 million doses per annually and planned to complete the construction of a second production facility by year-end 2020 to increase the yearly production capacity of CoronaVac to 600 million doses. Depending on market conditions and the availability of financing, Sinovac may seek to further expand the company’s production capacity.
A $500 million strategic partnership was forged with Sino Biopharmaceutical regarding Sinovac’s R&D subsidiary’s development of CoronaVac. In December, the subsidiary Sinovac Life Sciences secured funding for additional development, capacity expansion and manufacturing of CoronaVac, and to conduct other development and operational activities.