Interleukin-6(Pfizer Global Manufacturing China)

It was another busy week for clinical trial announcements. Here’s a look. COVID-19-Related CytoDyn announced that its Phase III trial of Vyrologix (leronlimab-PRO 140) demonstrated continued safety, substantial improvement in the survival rate, and faster hospital discharge in critically ill COVID-19 patients. The drug is a CCR5 antagonist being developed for several indications, including HIV and metastatic triple-negative breast cancer. The company also announced that 20 patients had been enrolled and dosed in the first 10 days of its Phase II trial for COVID-19 long-haulers syndrome. The trial will enroll 50 patients. Novavax announced that its COVID-19 vaccine had final efficacy of 96.4% against mild, moderate and severe COVID-19 caused by the original Wuhan wildtype strain in its UK pivotal Phase III trial. And after completing analysis of its Phase IIb trial in South Africa, it reported 55.4% efficacy among the HIV-negative trial volunteers in an area where the majority of strains were the South African B1.351 variants. Perhaps most importantly, across both trials, the Novavax vaccine was 100% protective against severe disease, including hospitalizations and death. Sanofi Pasteur and Translate Bio initiated their Phase I/II clinical trial of MRT5500, a messenger RNA (mRNA) vaccine candidate against COVID-19. The Phase I/II trial will include a total of 415 healthy adults 18 years of age and older and be enrolled across 13 sites. It requires two doses, 21 days apart. They will evaluate three different dose levels, 15 micrograms, 45 micrograms and 135 micrograms. Quantum Leap Healthcare Collaborative (QLHC) announced it will not continue with further testing of Aerpio Pharmaceuticals’ razuprotafib, which was part of the I-SPY COVID Trial. It is a Phase II adaptive trial that is testing various drugs that show promise of reducing the risk of death from and severe illness in COVID-19. The sponsor indicated the drug was challenging to administer in the COVID-19 setting, with 30% discontinuing the drug because of disease-related hypotension, including protocol-mandated stopping rules. There was no indication the drug caused the hypotension, but it was determined there was a small but clinically significant drop in systolic blood pressure and mean arterial blood pressure. Merck and Ridgeback Biotherapeutics announced preliminary results from Ridgeback’s Phase IIa trial of molnupiravir in COVID-19. They reported on one secondary objective, demonstrating a decrease in days to negativity of infectious virus isolation in nasopharyngeal swabs, as determined by isolation in Vero cell line culture. Molecular Partners AG and Novartis announced initial data from their ongoing Phase I trial of their tri-specific COVID-19 antiviral drug, ensovibep, in healthy volunteers. In the study, healthy volunteers were randomized 3:1 to receive an infusion of ensovibep or placebo, respectively. In both cohorts of two different doses of the drug, 3mg or 9mg per kilogram body weight, the drug was observed to be safe and well tolerated with no significant adverse events. The drug is designed to target multiple different sites on the SARS-CoV-2 virus simultaneously. It is formatted with a half-life extending DARPin domain that binds to human serum albumin (HSA) to support long-acting activity. Genentech, a Roche company, announced that its Phase III REMDACTA trial of Actemra (tocilizumab) plus Gilead Sciences’ Veklury (remdesivir) compared to placebo plus Veklury, failed to meet its primary endpoint in patients with severe COVID-19 pneumonia. The endpoint was measured by improved time to hospital discharge up to day 28 in this patient group receiving standard of care. Actemra is a humanized interleukin-6 (IL-6) receptor antagonist indicated for adults with moderately to severely active rheumatoid arthritis who have used one or more antirheumatic drugs, such as methotrexate, that did not provide enough relief. Vir Biotechnology and GlaxoSmithKline announced that an independent Data Monitoring Committee (IDMC) recommend their Phase III COMET-ICE trial of VIR-7831 as a monotherapy for early treatment of COVID-19 in adults at high risk be stopped for enrollment “due to evidence of profound efficacy.” The recommendation was based on interim analysis of data from 583 patients in the trial showing an 85% decrease in hospitalization or death in patients receiving the drug alone compared to placebo, which was the primary endpoint of the trial. The drug was well tolerated. VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. It appears to both block viral entry into healthy cells and improves the ability to clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1, the virus that causes SARS, suggesting it is highly conserved, and hopefully will make it more difficult for resistance to develop. Persephone Biosciences initiated the VOICES clinical study to determine the impact of gut microbiome composition and function on the immune system and efficacy of COVID-19 vaccination. The trial will enroll up to 10,000 people in the U.S being administered a COVID-19 vaccine. Blood and stool samples will be collected before and after the vaccinations with the goal of identifying and determining specific gut microbiota and the metabolic processes involved in optimal immune response and function. Rigel Pharmaceuticals completed patient enrollment in its Phase II trial of fostamatinib in hospitalized COVID-19 patients. Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor marketed in the U.S. as Tavalisse for adult chronic immune thrombocytopenia. Non-COVID-19-Related Mayne Pharma presented new data showing treatment with NEXTSTELLIS resulted in limited changes in endocrine markers, including lower increases in hormone-binding globulins, compared with combined oral contraceptives (COCs) based on etinyl-estradiol (EE), the synthetic estrogen used in all but one of the marketed COCs. NEXTSTELLIS is a novel COC containing drospirenone (DRSP) and estetrol (E4). Novartis announced that the Phase III CANOPY-2 trial of canakinumab failed to meet the primary endpoint of overall survival (OS). The drug was being evaluated in 237 adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease progressed while on or after previous platinum-based chemotherapy and checkpoint inhibitor immunotherapy. Canakinumab is a human monoclonal antibody that binds to human interleukin-1 and neutralizes its activity. By neutralizing IL-1beta, preliminary data suggested the drug would inhibit pro-tumor inflammation, improve anti-tumor immune response, decrease tumor cell proliferation, survival and invasiveness, and impair angiogenesis. The company plans to continue to analyze the data. Two Phase III CANOPY studies are continuing, testing the drug in first-line and adjuvant settings. ViiV Healthcare, majority-owned by GlaxoSmithKline, with Pfizer and Shionogi as shareholders, presented positive data from its Phase IIa proof-of-concept study of GSK-254 in HIV. The drug is an investigational maturation inhibitor. It demonstrated a relationship between dose and antiviral response with the 140mg and 200mg doses showing the greatest reduction in plasma HIV-1 RNA. Orca Therapeutics announced the independent Data and Safety Monitoring Board had reviewed its ongoing Phase I/IIa trial of ORCA-010 in treatment-naïve patients with localized prostate cancer and recommended continuation without modification. ORCA-010 is derived from the common cold virus adenovirus serotype 5 (Ad5) and then its DNA was modified in three places. TG Therapeutics published results from the UNITY-NHL Phase IIb trial of Ukoniq (umbralisib) in r/r indolent non-Hodgkin Lymphoma. The drug is a PI3k-delta and CK1-epsilon inhibitor. Clene and its subsidiary Clene Nanomedicine announced more than 50% of participants had been enrolled in the HEALEY ALS Platform Trial. It is a multi-center trial evaluating the safety and efficacy of multiple products in amyotrophic lateral sclerosis (ALS). CNM-Au8 was selected. It is a bioenergetic nanocatalyst, a stable, aqueous suspension of catalytically active gold (Au) nanocrystals. ORYZON Genomics presented new data from its Alzheimer’s trials with vafidemstat, ETHERAL and REIMAGINE-AD. The data confirmed previous findings on the safety of vafidemstat in these patients and its efficacy in controlling aggression and agitation. The drug modulates the histone-modifying enzyme LSD1. AEON Biopharma initiated enrollment in its Phase II trial of ABP-450 for the prevention of migraines. The drug contains a 900 kDa botulinum toxin type-A complex. Alkahest and a subsidiary of Grifols, presented data on its study of GRF6021 in Parkinson’s disease. The drug is a therapeutic plasma fraction candidate. Aravive dosed the first patient in its open-label Phase Ib/II trial of AVB-500 in advanced clear cell renal cell carcinoma patients that have progressed on front-line treatment. AVB-500 is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway associated with tumor cell growth. Merck presented results from a Phase I study of islatravir for pre-exposure prophylaxis of HIV-1 infection. Islatravir is a nucleoside reverse transcriptase translocation inhibitor. As a result, the company plans to initiate a Phase II trial. bluebird bio announced further analysis from its Phase I/II trial of LentiGlobin for sickle cell disease in regards to a case of acute myeloid leukemia (AML) that placed the study on clinical hold in February. Another patient in the study had also developed myelodysplastic syndrome. The new analysis indicated that the gene therapy was unlikely to be the cause of the AML. Aelix Therapeutics presented topline results from the Phase I/IIa AELIX-002 trial of its HTI T-cell therapeutic HIV vaccine in early-treated people living with HIV. The trial met its primary and secondary endpoints for safety, tolerability and immunogenicity. The data also suggested encouraging efficacy data. Transgene expanded its Phase II trial of TG4001 in combination with avelumab compared to avelumab monotherapy in patients with HPV16-positive anogenital cancers. The amendment allows a more rapid start. TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA) engineered to express HPV16 antigens E6 and E7 and an adjuvant (IL-2). Aligos Therapeutics began dosing the first cohort of chronic hepatitis B patients in its ongoing ALG-010133-101 study of ALG-010133. The drug is a proprietary olignonucleotide S-antigen Transport-inhibiting Olignonucleotide Polymer (STOPS) molecule that was developed to reduce viral S-antigen levels in hepatitis B patients. Agenus presented data on its Phase I/II trial of AGEN1181 in tumors previously unresponsive to immune therapies. AGEN1181 is the company’s Fc-enhanced next-generation anti-CTLA-4 antibody. The therapy was active even in patients with the low affinity FcyRIIIA allele and the drug demonstrated the ability to deplete intatumoral Tregs. Biohaven Pharmaceutical announced that more than 50% of participants had been enrolled in the verdiperstat regimen of HEALEY ALS Platform Trial, which is testing the efficacy of several treatments in amyotrophic lateral sclerosis (ALS). Verdipistat is a potential first-in-class, brain-penetrant, selective inhibitor of myeloperoxidase. Nouscom received approval from the regulatory authorities in Spain to launch a Phase Ib trial of NOUS-PEV. NOUS-PEV is a personalized cancer immunotherapy that will be evaluated in either locally advanced 1L melanoma or 1L non-small cell lung cancer (NSCLC). AVEO Oncology announced they had inked a clinical trial collaboration and supply deal with Bristol Myers Squibb to study Fotivda in combination with BMS’s checkpoint inhibitor Opdivo (nivolumab) in advanced r/r RCC after previous immunotherapy exposure. Earlier in the week, the FDA approved Fotivda for adults with relapsed or refractory advanced renal cell carcinoma (RCC) in people who have had two or more previous systemic therapies. The drug is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).

The Pfizer-BioNTech vaccine (now Comirnaty®) was fully approved by the U.S. Food and Drug Administration (FDA) on August 23 and boosters of this shot are now available to the most vulnerable Americans. This is an update of an article originally published on November 24, 2020, and a lot has happened! A novel virus means clinical research is playing out in real-time. The Pfizer - BioNTech vaccine (now Comirnaty®) was fully approved by the U.S. Food and Drug Administration (FDA) on August 23, boosters of this shot are now available to the most vulnerable Americans, and hope is on the horizon that hospitalization and death can largely be averted by a pill. But first, an update on the variant situation. A Note on Variants: In an effort to make it easier for the public and media to discuss variants, the World Health Organization convened experts from various organizations and internal divisions to “consider easy-to-pronounce and non-stigmatizing labels.” Which is why there are now Greek Alphabet names for the various variants, at least those that WHO has declared Variants of Concern (VOC) and Variants of Interest (VOI). Currently, the Delta variant is the only variant classified as a VOC in the United States, and there are no currently recognized VOIs. Wuhan or Wildtype The first strain to be identified that originated in the city of Wuhan, China. Delta (India) This is the variant still causing havoc across the U.S and much of the world. Dubbed a “double mutant” variant, Delta (B.1.617) has two key mutations observed in other coronavirus variants. The variant was actually first sequenced in a global database of COVID-19 variants in October 2020, but went largely unnoticed. The B.1.617 strain carries features from two lineages, the California variants (B.1.427 and B.1.429) and the ones in South Africa (B.1.351) and Brazil (P.1). The variant’s two prominent mutations include a position 452 of the spike protein and the second at 484. It is believed to be about 60% more contagious than the Alpha variant. As of September 25, the CDC estimated that Delta is responsible for more than 99% of all cases in the U.S. According to recent studies , the Pfizer-BioNTech vaccine is holding up against the Delta variant. AY.4.2 (Delta-Plus). A subvariant of the Delta variant, as of October 21, 2021, it has been observed in the UK, Denmark and the U.S. Very little is known about its transmissibility, although there is speculation it might be 10% more transmissible than Delta. Past Variants of Concern Alpha (UK) Dubbed B.1.1.7, the UK variant was first identified in the fall of 2020. It spreads more easily and quickly than other variants, according to the CDC, and is potentially 30% more lethal than the wildtype version, although that is still being investigated. It was first detected in the U.S. at the end of December 2020. Beta (South Africa) Originally B.1.351, Beta emerged independently of B.1.1.7 (UK) and was first detected in South Africa in early October 2020. It shares some of the same mutations as the UK strain. Cases in the U.S. were first reported at the end of January 2021. Current evidence suggests it does respond to vaccines, but can evade antibodies generated by the immune system against the original SARS-CoV-2 virus due to its E484K mutation. Gamma (Brazil) The Brazilian, originally P.1, was first identified in people traveling from Brazil during routine testing in Japan, in early January. It appears to have a group of additional mutations (including E484K and N501Y) that affect its ability to be recognized by antibodies, according to the CDC. It was first observed in the U.S. at the end of January 2021. Iota (New York) This variant first appeared in New York City and then sporadically in the northeast. It was named B.1.526. It also contains the E484K mutation, which has been observed in at least 59 different lineages of coronavirus. This means it is evolving independently around the world in what is called convergent evolution. Mu Mu, or B.1.621, in September 2021 was categorized by the WHO as a “variant of interest.” It appeared to originate in January 2021, in Columbia, but does not appear to have spread much around the world. California This variant was called B.1.427/B.1.429 and appeared different than the UK variant. One of the mutations, called L452R, affects the virus’s spike protein, which may allow it to attach itself more efficiently to cells, making it more infectious. Like with the New York variant, the data had not been peer-reviewed at the time of publication. However, it appeared to be associated with severity of disease and increased risk of high oxygen requirement. In particular, the virus appeared to be prevalent in the San Francisco area. A Note on Pricing The prices listed, for the most part, are the prices that were known at the time this article was first published. Because of multiple contracts by various governments and how they are being reimbursed, there is significant variability in actual prices. Some have significantly dropped since the original publication and appear to be changing regularly. Also, there are considerable variations in pricing from country to country. If you find any variations or inaccuracies, please let us know. A Note on the Vaccine Market and Sales Getting a handle on the COVID-19 vaccine market and sales is definitely a moving target, with governments subsidizing manufacturing and distribution, and prices varying from country to country. According to Morningstar, the 2021 vaccine market will max out at $67 billion, and 2022 will see this drop to $61 billion. Morningstar noted on May 3, 2021 that the Pfizer-BioNTech and Moderna COVID-19 vaccines account for more than 60% of the total COVID-19 market estimate in 2021 and 2022. More recently, InsightAce Analytic projected that the global COVID-19 therapeutics market size would reach $25.6 Billion in 2030. The numbers by research firm vary greatly, with many projecting a drop-off in 2023 as more people, particularly in developing nations, become vaccinated. The 10 best-selling COVID-19 vaccines and drugs in the first half of 2021 are: 1 . Pfizer-BioNTech COVID-19 vaccine (Comirnaty®): Worldwide sales were $19.927 billion . GlobalData Healthcare projects that Comirnaty will bring in $100 billion in sales between 2020 to 2027, with a large portion of the revenue driven by the 2021-2024 time period. 2 . Moderna COVID-19 vaccine: Worldwide sales equaled $5.93 billion. U.S. Sales amounted to 58% of the pie at $3.451 billion. 3 . Regeneron Pharmaceuticals ’ casirivimab and imdevimab (REGEN-COV): Regeneron’s antibody cocktail reported $4.156 billion in global revenue and $2.853 billion in U.S. sales alone. 4 . Gilead Sciences ’ remdesivir (Veklury): Global sales totaled $2.285 billion for the antiviral drug. U.S. sales accounted for 54% at $1.236 billion. 5. Roche and Genentech ’s Actemra ® / RoActemra® (toclizumab): The Interleukin-6 (IL-6) receptor antagonist brought in $1.789 billion globally and $751 million in U.S. sales. 6 . AstraZeneca -Oxford COVID-19 vaccine: Worldwide, the viral vector shot brought in $1.135 billion in global sales. This vaccine is not currently approved in the U.S. 7 . Eli Lilly bamlanivimab and etesevimab: The antibody cocktail brought in $959.1 million in worldwide sales. U.S. sales were $734 million. 8 . Eli Lilly ’s Olumiant (baricitinib): Lilly’s Janus kinase (JAK) inhibitor earned $402.2 million worldwide, with just $42.5 million coming from U.S. sales. 9. Johnson & Johnson ( Janssen ) Vaccine: The single-shot vaccine brought in $264 million globally, with $151 million of the revenue coming from the U.S. J&J reported $502 million in sales of its COVID-19 vaccine in the third quarter of 2021. 10. Celltrion Healthcare ’s antiviral Regkirona® (regdanvimab; CT-P59): Netted global sales of $37.6 million. Vaccine Details Pfizer-BioNTech ( Comirnaty®) The Pfizer-BioNTech COVID-19 vaccine was sent to the FDA for possible Emergency Use Authorization (EUA) on Friday, November 20 and authorized on December 11. It received full approval on August 23, 2021 and became known by its brand name, Comirnaty. It is an mRNA vaccine that codes for the virus’s spike protein and is encapsulated in a lipid nanoparticle. Once injected, the cells churn out the spike protein, triggering the body’s immune system to recognize the virus. In Phase III trials, it demonstrated 95% efficacy. The Pfizer-BioNTech vaccine requires storage at about -94 degrees F, which requires specialized freezers. Now authorized in the U.S. for adolescents 12 to 15 years of age. The Pfizer-BioNTech and Moderna COVID-19 vaccines have been associated with very rare cases of myocarditis (heart inflammation) in some young adults and teenagers, although the association has been called “likely.” On September 23, the FDA authorized a booster shot of the Pfizer-BioNTech vaccine for people over the age of 65, individuals at high risk for severe disease and front-line healthcare workers six months after they received their second dose. The following day, the CDC added a group, recommending boosters for people between the ages of 18 and 64 who are at increased risk of COVID-19 due to their work or living situation. The FDA has also authorized mixing-and-matching vaccines as boosters. Type: mRNA Doses: 2, 21 Days Apart EUA Date: December 11, 2020 Full Approval Date : August 23, 2021. Price: $19.50 per dose for first 100 million doses. Projections : At Pfizer’s second-quarter earnings report, it forecasted 2021 sales of the COVID-19 vaccine to be $33.5 billion. Efficacy: About 95%. Apparently 100% at preventing hospitalization and death. Variants: Lab data suggest “quite effective” against the Alpha variant as well as the Beta and Gamma variants. Also, data suggests it is effective against hospitalization in cases caused by the Delta variant but more data is needed. Moderna On November 16, 2020, Moderna issued a preliminary data readout out of its COVID-19 vaccine, suggesting an efficacy rate of 94.5%. It was authorized by the FDA on December 19. Like the Pfizer-BioNTech vaccine, it is an mRNA vaccine. Unlike that shot, however, the Moderna vaccine is stable at 36 to 46 degrees F, about the temperature of a standard home or medical refrigerator, for up to 30 days and can be stored for up to six months at -4 degrees F. In May 2021, Moderna reported that a Phase II/III trial of 3,732 children ages 12 to 17 in the U.S. demonstrated its vaccine produced an immune response equivalent to earlier findings in adults. Data also suggested the vaccine was 93% effective after one dose at preventing mild COVID-19 cases. It was generally well-tolerated. Moderna filed for an EUA for the vaccine in adolescents on June 10, 2021. In October 2021, the FDA authorized the Moderna vaccine for people who are immunosuppressed, people over the age of 65, people at high risk of severe disease, front-line healthcare workers, and for people between the ages of 18 and 64 who are at increased risk of COVID-19 due to their work or living situation. The FDA has also authorized mixing-and-matching vaccines as boosters. Type: mRNA Doses: 2, 28 Days Apart EUA Date: December 18, 2020 Price: $25-$37 per dose Projections : At its second-quarter earnings report, Moderna projected $19.2 billion in COVID-19 vaccine sales for 2021. Efficacy: About 95%. Apparently 100% at preventing hospitalization and death. Variants: Lab data suggest “quite effective” against the Alpha variant as well as the Beta and Gamma variants. Also, data suggests it is effective against hospitalization in cases caused by the Delta variant but more data is needed. Johnson & Johnson Projections : On February 27, the FDA approved Johnson & Johnson (Janssen’s) COVID-19 vaccine under EUA. Whereas the Pfizer-BioNTech, Moderna and AstraZeneca vaccines all require two doses about 28 days apart, the J&J vaccine requires only a single dose. The Phase III ENSEMBLE trial demonstrated the single-shot vaccine is 66% effective overall in preventing moderate-to-severe COVID-19, 28 days after vaccination. However, it demonstrated 100% efficacy at preventing severe disease after day 49. The vaccine uses the company’s AdVac technology platform, which it used to develop its approved Ebola vaccine and its Zika, RSV and HIV investigational vaccine candidates. It revolves around the use of an inactivated common cold virus, similar to what the AstraZeneca-University of Oxford program utilizes. In April 2021, the CDC and FDA recommended a pause on distribution of the vaccine. Six cases of a “rare and severe” type of blood clot had been identified. The clots observed with the J&J vaccine are cerebral venous sinus thrombosis (CVST) in combination with low levels of blood platelets, called thrombocytopenia. All six of the cases were in women between the ages of 18 and 48 and occurred six to 13 days after receiving the single-dose vaccine. These six cases were extremely rare among the more than seven million doses administered. The FDA and CDC had placed a pause on the J&J vaccine on April 13 over six reported cases of a “rare and severe” blood clot known as cerebral venous sinus thrombosis (CVST) in combination with low levels of blood platelets (thrombocytopenia). On April 23, they lifted the restrictions, saying that the benefits outweighed the risks. In July, the FDA planned a new warning for the J&J vaccine over a rare but serious side effect, Guillain-Barré syndrome (GBS). Guillain-Barré syndrome, which has been linked to other vaccines in the past, is a rare neurological disorder where the immune system attacks part of the peripheral nervous system. Approximately 100 preliminary reports of GBS have been identified out of 12.8 million doses of the J&J vaccine in the U.S., according to the CDC. They appear about two weeks after vaccination and primarily in men, most 50 years of age and older. In October 2021, the FDA authorized the J&J vaccine for people who are immunosuppressed, people over the age of 65, people at high risk of severe disease, front-line healthcare workers, and for people between the ages of 18 and 64 who are at increased risk of COVID-19 due to their work or living situation. The FDA has also authorized mixing-and-matching vaccines as boosters. Type: Adenovirus-based Doses: 1 Authorized Under EUA. Price: $10 per dose Projections : At its half-year earnings report 2021, J&J estimated full-year vaccine sales of $2.5 billion. Efficacy: In J&J’s global clinical trial, the vaccine demonstrated 66% efficacy at preventing symptomatic COVID-19 infections. In the U.S. it was slightly higher at 72%. It appears to be 100% effective at preventing hospitalizations and death. Variants: Based on clinical studies in Africa, UK and Latin America, there is evidence the vaccine is effective against the variants, although less so against the Beta and Gamma strains. The table below shows the comparison of EUA approved vaccines in the U.S. COMPANY PFIZER/BIONTECH MODERNA J&J/JANSSEN Research Name BNT162b2 mRNA-1273 Ad26.CoV2.S Name Comirnaty Spikevax Janssen COVID-19 vaccine Type mRNA mRNA viral vector EUA Approved 12/11/2020 12/18/2020 2/27/2021 FDA Fully Approved 8/23/2021 (for people ages 16 and older) No, but been submitted No, be submitted later this year Authorized Ages 5 and older 18 and older Delayed decision for children 12-17 years old (could be Jan. 2022) 18 and older Authorized Ages for Booster Yes, for all (ages 16 and up) Yes Yes # of Doses 2 (21 days apart) 2 (28 days apart) 1 Efficacy* 91.3% to 95% at preventing symptomatic disease; 100% at preventing severe disease as defined by CDC, 95.3% as defined by FDA 95% symptomatic, 96.3% to 100% at preventing hospitalization and death 28 days after inoculation: 85.4% for severe disease and 93.1% against hospitalization Efficacy Against Delta Variant* Early research suggests 88% efficacy at preventing symptomatic COVID-19 virus & 96% efficacy against hospitalization Early research suggests 72% efficacy at preventing symptomatic COVID-19 virus According to J&J research, 85% effective at preventing severe disease, up to 95% for preventing death Common Side Effects At site of injection: Pain, swelling, redness Other: Tiredness, headache, muscle pain, chills, fever, nausea, swollen lymph nodes At site of injection: pain, swelling, redness Other: tiredness, headache, muscle pain, chills, fever, nausea, swollen lymph nodes Injection site pain, headache, fatigue, myalgia, nausea, swollen lymph nodes Rare Side Effects Allergic reaction, myocarditis, pericarditis, swollen lymph nodes, decreased appetite, diarrhea, vomiting, fainting due to shot Allergic reaction, myocarditis & pericarditis in adolescents and young adults (~12.6 cases per million 2nd dose administered) Anaphylaxis and severe allergic reaction, blood clots, Thrombosis with Thrombocytopenia syndrome usually occurring in women younger than 50, Guillain-Barré syndrome, capillary leak syndrome, fainting due to shot Price $19.50 per dose $25-$37 per dose $10 per dose Projected Sales $33.5 billion for 2021 $19.2 billion for 2021 $2.5 billion for 2021 # of Fully Vaccinated in U.S. (Source: CDC data as of 12/13/21) 113,046,986 72,677,133 16,117,973 * Dozens of studies have been conducted on the efficacy of the vaccines, within structured clinical trials, real-world studies, and laboratory assays. The stated efficacy values generally reflect a consensus range, which can vary depending on study structure, patient population and most common circulating viral variant at the time of the study. AstraZeneca-University of Oxford On November 23, AstraZeneca and the University of Oxford announced high-level results from an interim analysis of their COVID-19 vaccine, AZD1222. The analysis was from the trials in the UK and Brazil and demonstrated efficacy of up to 90%. The vaccine was effective at preventing COVID-19, with no hospitalizations or severe cases in people receiving it. There were a total of 131 COVID-19 positive cases in the interim analysis group. One dosing regimen was given at a half dose and demonstrated 90% efficacy, followed by a full dose at least one month apart. Another dosing regimen demonstrated 62% efficacy when two full doses were given at least one month apart. The combined analysis showed average efficacy of 70%. The AstraZeneca vaccine can be stored, transported and handled at normal refrigerated conditions, about 36-46 degrees F, for at least six months and administered within existing healthcare settings. On March 25, 2021, AstraZeneca released primary analysis showing that the vaccine demonstrated 76% efficacy against symptomatic COVID-19, 100% efficacy against severe or critical disease and hospitalizations, and 85% efficacy against symptomatic COVID-19 in people 65 years and older. The AstraZeneca and University of Oxford’s vaccine uses technology from an Oxford spinout company, Vaccitech . It deploys a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees. It contains the genetic materials of the spike protein. After vaccination, the cells produce the spike protein, stimulating the immune system to attack the SARS-CoV-2 virus. The COVID-19 vaccine developed by AstraZeneca and the University of Oxford has been linked to blood clots. More than a dozen European countries have halted the distribution of the AstraZeneca-Oxford vaccine as a result. In May in England, it was recommended that people under the age of 40 should receive a different vaccine due to blood clots. There was a report of an arterial stroke in the UK published online in Journal of Neurology Neurosurgery & Psychiatry in late May. The most recent data, from July 2021, indicates that the risks of clotting combined with low blood platelets (vaccine-induced immune thrombotic thrombocytopenia, or VITT) are about 1 to 2 per 100,000 vaccinations, in the UK and Europe. Type: Adenovirus-based Doses: 2, 28 Days Apart Likely FDA Authorization Date: Authorized in Europe on January 12, 2021, and other countries, but unlikely in the U.S. The delay is due to AstraZeneca’s decision to request full approval in the U.S. As of October 21, 2021, AstraZeneca-Oxford have not filed in the U.S. for EUA. Price: $2.15 (U.S.) in the EU; $3-4 (U.S.) in the UK and U.S.; $5.25 (U.S.) in South Africa During the first half of 2021, AstraZeneca and the University of Oxford reported $1.135 billion in global sales. Analyst projections suggest annual sales will be $1.5 billion to $2.5 billion. Efficacy: Currently about 70% overall. Variants: At least one study finds it has little effect against the Beta variant, but appears effective against the Alpha and Gamma variants. Russia’s Sputnik V Vaccine Around November 11, 2020, Russia’s National Research Center for Epidemiology and Microbiology claimed Sputnik V had an efficacy rate of 92% after the second dose. The vaccine was authorized for use in Russia in August 2020 before even the beginning of a Phase III trial. The updated efficacy evaluation was based on a first interim analysis 21 days after the first injection during the ongoing Phase III study. On November 24, the organization claimed 95% efficacy based on new preliminary data. On December 14, 2020, they reported efficacy of 91.4%. It also offered to share one of its two human adenoviral vectors with AstraZeneca to increase the efficacy of the AstraZeneca vaccine. Russia’s Gamaleya research institute appears to be focused on potentially marketing their vaccine worldwide. Even the name of the vaccine has emphasized the idea of a race. The organization has indicated a dose of the vaccine will cost no more than $10, about half the cost of the Pfizer vaccine. The organization has also predicted it could produce 1 billion doses in the next year. On February 2, 2021, The Lancet published Phase III data demonstrating a 91.6% efficacy against the original strain of the virus. This vaccine, even into mid-July 2021, remains controversial . It is being distributed in 39 countries and is expected to be distributed in 27 more. However, inconsistent clinical trial data has scientists questioning the analyses and wondering if it has been manipulated. It was originally authorized in Russia in August 2020 after being tested on only 38 people. The Gamaleya Research Institute published results showing 95% efficacy in The Lancet but did not include raw data. In mid-May, a group of international scientists highlighted concerns over patterns in The Lancet data consistent with data manipulation. Even though some studies have been published about the Sputnik V vaccine, Reuters noted as of July 13 that the vaccine’s Russian developers have repeatedly failed to provide the necessary data for regulators in Europe to assess it appropriately. As of October 21, 2021, the Europe has indicated they do not expect authorization until early 2022 due to missing data. Type: Adenovirus-based Doses: 2 Likely EUA Date: Not applicable in the U.S. Price: $10 per dose Efficacy: 91.4% Variants: Unknown. Clinical trial data was largely conducted in Russia prior to the emergence of major variants. Sinovac Biotech On January 13, 2021, China-based Sinovac Biotech reported that its COVID-19 vaccine had a 50.38% efficacy in late-stage clinical trials in Brazil. The company’s clinical trials are demonstrating dramatically varying efficacy rates . In Indonesia, a local trial demonstrated an efficacy rate of 65%, but the trial had only 1,620 participants. Turkey reported an efficacy rate of 91.25% in December 2020. Another trial in Brazil run by a local partner, Butantan Institute, reported a 78% efficacy rate in mild cases while 100% against severe and moderate infections. It is an inactivated vaccine that uses inactivated SARS-CoV-2 viruses. In May 2021, WHO requested more data from the company regarding the safety of the shot and its manufacturing process. They want to determine if it is compliant with WHO standards and expect to make a decision in June. As of mid-July 2021, WHO studies showed the Sinovac vaccine “prevented symptomatic disease in 51% of those vaccinated and prevented severe COVID-19 and hospitalization in 100% of the studied population” for adults aged 18 and older. However, few adults over the age of 60 were enrolled in the trials, so efficacy could not be evaluated for that age group. Type: Inactivated SARS-CoV-2 virus Doses: 2 Likely EUA Date: Not applicable in the U.S. Price: $60 per dose in China ($29.75 per dose) Efficacy: 50.38% to 91.25%, depending on the clinical trial Variants: Unknown, although a study in Brazil demonstrated 50.4% efficacy at preventing symptomatic infections. Novavax On January 28, 2021, Novavax announced that its protein-based COVID-19 vaccine, NVX-CoV2373, hit the primary endpoint with an efficacy of 89.3% in its Phase III trial in the UK. It also has amassed data from the South Africa Phase IIb trial and several Phase I, II and III trials. It has demonstrated high clinical efficacy against the Alpha and Beta variants as well. The vaccine contains a full-length, prefusion spike protein made using the company’s recombinant nanoparticle technology and its proprietary saponin-based Matrix-M adjuvant. It is stable at 2 to 8 degrees C and shipped in a ready-to-use liquid formulation. With the U.S. largely covered, Novavax is now expected to delay its filing with the FDA until the fourth quarter of 2021. On September 23, Novavax, along with partner Serum Institute of India, filed with WHO for Emergency Use Listing. In October 2021, there were reports that the company was having problems getting its COVID-19 vaccine to the finish line due to manufacturing issues. In addition to an expected submission to the U.S. Food and Drug Administration (FDA) before the end of 2021, it has ongoing rolling submissions in the UK, Europe, Canada, Australia and New Zealand which is expects to wrap in late October 2021/early November 2021, and has already made submissions in Indian, Indonesia and The Philippines in addition to an Emergency Use Listing (EUL) with the World Health Organization (WHO). Type: Protein-based vaccine Doses: 2 Likely EUA Date: Expected to file Q4, 2021. Price: $16 in the US Efficacy: 90.4% Variants: Effective against Alpha and Beta variants. CanSino Biologics CanSino Biologics’ vaccine was co-developed with the Chinese military. It has an efficacy rate of 65.7% at preventing symptomatic cases. This is based on a multi-country analysis first posted on Twitter by Faisal Sultan, Pakistan’s health adviser, on February 8, 2021. The Phase III trial includes 30,000 participants and demonstrated 90.98% efficacy in preventing severe disease. It only requires a single shot. CanSino has agreed to supply 35 million doses to Mexico and is in talks with Malaysia for 3.5 million shots. Pakistan is running one of the largest trials and has contracted for 20 million shots. It is also working with the WHO for approval for the vaccine through the Covax program. It is also planning a trial with Russia to determine if swapping the second dose of Russia’s Sputnik V vaccine with Can Sino would produce the same or better protection. In a trial in February, the vaccine demonstrated efficacy of 65.7% in preventing symptomatic cases. But in April, the company noted that its efficacy rate seemed to drop over time, but should have a rate of 50% or more five to six months after inoculation. According to a study out of Mexico’s National Institute of Medical Sciences and Nutrition, the CanSino vaccine only offers protection for about six months. They also believe that a second dose of the vaccine would likely be necessary. Type: Viral vector, loading an antigen from the SARS-CoV-2 virus onto an adenovirus. Doses: 1 Price: Unknown Likely EUA Date: Not applicable in the U.S. Efficacy: 65.7% at preventing symptomatic cases; 90.98% efficacy in preventing severe disease. Variants: Unknown Bharat Biotech On April 22, 2021, India’s Bharat Biotech reported interim data from the Phase III trial of its COVID-19 vaccine COVAXIN, which demonstrated a 100% efficacy against severe infection. The vaccine was developed with seed strains from the Indian Council of Medical Research’s (ICMR) National Institute of Virology. It is a highly purified and inactivated vaccine. A second interim analysis suggested a 78% efficacy against mild, moderate and severe disease, and 70% efficacy against asymptomatic disease. It does not require sub-zero storage or reconstitution requirement and is ready to use liquid in multi-dose vials. It is stable at 2-8 degrees C. As of July 9, the company reportedly submitted all documents required for Emergency Use Listing (EUL) to WHO. India’s Bharat Biotech announced in October 2021, that it had delivered one billion doses of its COVID-19 vaccine, Covaxin, in only nine months. In the same month, India’s regulatory body approved Covaxin for children 2 to 18 years of age in India. A review of its efficacy indicated it was similar in children to what was seen in adults. This was an emergency use authorization. It is the second vaccine against COVID-19 granted emergency use authorization for children in India, the first being Zydus Healthcare’s ZyCoV-D. Type: Inactivated SARS-CoV-2 virus using Whole-Virion Inactivated Vero Cell platform technology. Doses: 2, 28 days apart Likely EUA Date: Not applicable in the U.S. Price: ₹150 or about $2 (U.S.), although that appears to be the low-end of the open-market price in India Efficacy: 100% against severe infection; 78% against mild, moderate and severe; 70% against asymptomatic Variants: Wildtype; can neutralize Alpha variant Abdala and Soberana 2 Vaccines The Cuban government announced on June 22, 2021 that its three-shot Abdala vaccine has a 92% efficacy rate against COVID-19. They provided no details on clinical testing. It also announced that another of its COVID-19 vaccines, Soberana 2, had an efficacy of 62% after two of its three shots. Abdala is created by Cuba’s Center for Genetic Engineering and Biotechnology. Soberana 2 was developed by a state-run biopharma company, BioCubaFarma, which oversees the Finlay Institute and Center for Genetic Engineering and Biotechnology. Reportedly, Cuba has five coronavirus vaccine candidates.