Covaxin COVID-19 Vaccine Description
Bharat Biotech’s Covaxin (BBV152) is an inactivated COVID-19 vaccine that uses adjuvant Alhydroxiquim-II to boost immune response longer-lasting immunity. The Indian Council of Medical Research created the Covaxin (BBV152) vaccine.
The candidate, a whole virion inactivated SARS-CoV-2 vaccine, was developed from a well-known SARS-CoV-2 strain (NIV-2020-770) and a Vero cell platform (CCL-81) with adjuncts of either aluminum hydroxide gel (Algel) or a novel TLR7/8 agonist adsorbed gel. The SARS-CoV-2 virus strain was isolated from an asymptomatic COVID-19 patient at the National Institute of Virology, an Indian virology research institute.
The TLR7/8 adjuvant formulation specifically induced significant Th1 biased antibody responses and increased SARS-CoV-2 lymphocyte responses.
The components of the vaccine include BBV152A, BBV152B, and BBV152C.
In preclinical studies and animal challenge models (Syrian Hamster and Rhesus Macaques), the company showed that Covaxin (BBV152) induced Th1 based response due to Algel-IMDG (chemosorbed imidazoquinoline onto the aluminum hydroxide gel) as an adjuvant.
On March 8, 2021, The Lancet published a study 'Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomized, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomized phase 1 trial.' This study concluded by saying, 'In the phase 1 trial, BBV152 induced high neutralizing antibody responses that remained elevated in all participants at 3 months after the second vaccination. In the phase 2 trial, BBV152 showed better reactogenicity and safety outcomes and enhanced humoral and cell-mediated immune responses compared with the phase 1 trial. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial.'
Covaxin (BBV152) Accession Number: DB15847
Covaxin COVID-19 Vaccine History
On September 28, 2020, ViroVax LLC licensed its adjuvant, Alhydroxiquim-II technology, to Bharat Biotech to produce Covaxin. The Accession Number is DB15847.
News agency PTI reported on November 1, 2020: "If we get all the approvals after establishing strong experimental evidence and data, and efficacy and safety data in our last stage of trials, we aim to launch the vaccine in Q2 of 2021," Sai Prasad, executive director, Bharat Biotech International Ltd, told the news agency.
“COVAXIN™ utilizes a historically proven approach to vaccine design. The adjuvanted inactivated virus vaccine candidate elicited strong IgG responses against spike protein, receptor-binding domain, and the nucleocapsid protein of SARS-CoV-2 along with strong cellular responses in Phase 1 and 2 clinical trials. COVAXIN™ offers a vaccine candidate that is different from other options currently available in the US market with potentially broader coverage against multiple protein antigens of the virus,” said Harvey Rubin, M.D. Ph.D. of the University of Pennsylvania, a member of Ocugen’s Vaccine Scientific Advisory Board, on December 22, 2020.
Bharat Biotech is currently conducting Phase III human trials of COVAXIN in 26,000 participants in over 25 centers across India after receiving India's Drug Controller General's approval.
The indigenous inactivated vaccine was developed and manufactured in Bharat Biotech’s Bio-Safety Level 3 High-Containment facility located in Genome Valley, Hyderabad, India.
On December 22, 2020, Pennsylvania-based Ocugen, Inc. announced that it had signed a binding letter of intent to co-develop Bharat Biotech’s COVID-19 vaccine candidate, COVAXIN, an advanced stage whole-viron inactivated vaccine candidate, for the United States market. The collaboration will leverage the vaccine expertise of Ocugen’s leadership team. In preparation for the development of COVAXIN™ in the US, Ocugen’s Vaccine Scientific Advisory Board and Ocugen management have initiated discussions with the U.S. Food & Drug Administration (FDA) and the Biomedical Advanced Research and Development Authority (BARDA) to develop a regulatory path to EUA and, eventually, biologics license application (BLA) approval in the US market for COVAXIN™. Ocugen is also in active discussions with manufacturers in the US to produce a significant number of doses of COVAXIN™ to support its US immunization program.
On January 3, 2021, the Central Drugs Standard Control Organisation in India recommended emergency use permission.
“The evaluation of COVAXIN™ has resulted in several unique product characteristics, including long-term persistence of immune responses to multiple viral proteins, as opposed to only the spike protein, and has demonstrated broad-spectrum neutralizing capability with heterologous SARS-CoV-2 strains, thus potentially reducing or eliminating escape mutants. Requiring only a standard vaccine storage temperature of 2-8oC and with the potential to treat all age-groups, COVAXIN™ may offer an important option to protect lives across America,” said Dr. Shankar Musunuri, Chairman, CEO, and Co-Founder of Ocugen, in a press statement issued on February 2, 2021.
Hyderabad-based Bharat Biotech creates innovative vaccines and bio-therapeutics trusted by physicians worldwide.
Covaxin COVID-19 Vaccine Indication
The Covaxin vaccine is indicated to prevent infection from the SARS-CoV-2 beta coronavirus that causes COVID-19 disease in humans.
No pediatric or pregnancy vaccine efficacy data has been released.
Covaxin - Ocugen Distribution Agreement
Ocugen, Inc., a Pennsylvania-based biopharmaceutical company focused on discovering, developing, and commercializing gene therapies to cure blindness diseases and developing a vaccine to fight COVID-19, and India-based Bharat Biotech, announced on February 2, 2021, they have entered into a definitive agreement to co-develop, supply, and commercialize Bharat Biotech’s COVAXIN for the United States market. Under the terms of the agreement, Ocugen will have US rights to the vaccine candidate and will be responsible for clinical development, regulatory approval, and commercialization for the USA.
On March 14, 2021, Ocugen's CEO Shankar Musunuri told Reuters ' the company seeks to sell 100 million doses of Covaxin in the USA in 2021.
"We are actively working with U.S. regulatory authorities to develop a plan around Emergency Use Authorization in the United States for COVAXIN™ and are preparing to file an Investigational New Drug application to initiate our first two clinical trials for OCU400 in the second half of this year. Proceeds from our recent registered direct offering provide the financial resources to drive our COVAXIN™ development efforts and ophthalmology pipeline forward,” said Dr. Shankar Musunuri in a press statement issued on March 18, 2021.
Covaxin COVID-19 Vaccine News
March 19, 2021 - Nepal's Department of Drug Administration issued emergency authorization for the Covaxin COVID-19 vaccine.
March 18, 2021 - Malvern, PA-based Ocugen, Inc. announced it had established a vaccine scientific advisory board composed of leading academic and industry experts with extensive experience in the vaccine field. Collectively, the team is working with U.S. regulatory authorities to develop the regulatory pathway to EUA in the U.S. market for the Covaxin vaccine.
March 8, 2021 - The Lancet reported: The BBV152 vaccine, adjuvanted with alum and a TLR 7/8 agonist, is designed to enhance humoral and Th1-skewed cellular immune responses after immunization by optimizing the inactivated vaccine formulation. Overall, Algel-IMDG-adjuvanted BBV152 was safe, immunogenic, and able to induce Th1-biased T-cell responses and could be a potentially superior vaccine over the alum-adjuvanted inactivated COVID-19 vaccines. However, this is the only study of an inactivated COVID-19 vaccine candidate to report a thorough evaluation of cell-mediated responses. The 6 μg with Algel-IMDG formulation has been selected for the phase 3 efficacy trial. BBV152 (developed using a well-established manufacturing platform) was safe, immunogenic (persisting for 3 months), and can be stored at 2–8°C, which is compatible with most of the immunization cold chain requirements countries. Follow-up studies to assess the efficacy and immune responses in older adults and people with comorbidities are underway.
March 3, 2021 - Bharat Biotech announced the first interim analysis of its BBV152 (COVAXIN®). The whole virion inactivated COVID-19 vaccine candidate demonstrated an interim vaccine efficacy of 81% in its Phase 3 clinical trial. The trials involved 25,800 subjects, the largest ever conducted in India, in partnership with the Indian Council of Medical Research. The first interim analysis is based on 43 cases, of which 36 cases of COVID-19 were observed in the placebo group versus 7 cases observed in the BBV152 (COVAXIN®) group, resulting in a point estimate of vaccine efficacy of 80.6%. An interim analysis is planned for 87 cases, and the final analysis is planned for 130 cases. All data from the second interim and final analyses will be shared via prepublication servers and submitted to a peer-reviewed journal for publication.
March 2, 2021 - The journal Nature published a study: Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Altogether, this study demonstrates that a two-dose vaccination regimen using a 3-µg dose of the vaccine candidate with adjuvant B induces a significant immune response and provides effective protection in animals challenged with SARS-CoV-2.
February 26, 2021 - Brazil's health ministry announced it signed a contract to purchase 20 million doses of the Covaxin vaccine for delivery between March and May 2021.
February 19, 2021 - The Indian Council of Medical Research (ICMR) announced interim results of the ongoing Covaxin vaccine clinical trials indicated that the indigenous Covid-19 vaccine would be effective against SARS-CoV-2 coronavirus strains reported from the United Kingdom, South Africa, and Brazil. The third clinical trial of Covaxin had been completed as all the 25,800 volunteers involved had been administered both doses, reported The Hindustan Times.
February 18, 2021 - Reuters reported Bharat Biotech announced it is in the process of filing regulatory documents for approval of its COVID-19 vaccine, COVAXIN, in more than 40 countries.
February 2, 2021 - Ocugen, Inc. and Bharat Biotech announced they have entered into a definitive agreement to codevelop, supply, and commercialize Bharat Biotech’s COVAXIN™, an advanced stage whole-virion inactivated COVID-19 vaccine candidate, for the United States market.
January 31, 2021 - As part of the India-developed COVID-19 vaccine Covaxin, India's Bharat Biotech has applied for "Emergency Use Authorization" (EUA) in the Philippines. This is the first international regulatory filing for Bharat biotech's COVAXIN.
January 23, 2021 - The Lancet published an article: 'COVAXIN's approval in India came before the company had finished recruiting for the drug's phase 3 trial. Given that there is no efficacy data for COVAXIN yet, some health workers “may not have confidence in COVAXIN, and that is understandable,” said Vineeta Bal, immunologist and visiting faculty from the Indian Institute of Science Education and Research, Pune. “The government needs to put out all data, including for efficacy, for the sake of transparency and for building the confidence of the people,” she said. “The lack of data for COVAXIN leaves those who have been given it in an uncertain position regarding their status. The vaccine may work out to be safe and efficacious, but that would be owed more to good luck than to good government policy”, said Jammi Nagaraj Rao, a public health physician and epidemiologist.'
January 21, 2021 - India’s envoy to the Philippines, Shambhu Kumaran, said in a tweet: “A proud moment for Indian R&D! The first international regulatory filing for COVAXIN. Delighted that it is in the Philippines, a vital partner of the ‘Indo-Pacific. The process ahead will be difficult, but today we celebrate those who made this milestone possible!" Once Covaxin is approved by the local regulator, India is expected to donate certain vaccine doses and open the door to exports on a commercial basis.
January 21, 2021 - The Lancet published a 'report on the interim findings from the phase 1 clinical trial of BBV152; a whole-virion inactivated SARS-CoV-2 vaccine. The vaccine was well tolerated in all dose groups with no vaccine-related serious adverse events. Both humoral and cell-mediated responses were observed in the Algel-IMDG-based vaccine recipients. The most common adverse event was pain at the injection site, followed by headache, fatigue, and fever. The overall incidence of solicited local and systemic adverse events in this study was 14–21% in all vaccine-treated groups, which is noticeably lower than the rates for other SARS-CoV-2 vaccine platform candidates and similar to the rates for other inactivated SARS-CoV-2 vaccine candidates. BBV152 induced binding and neutralizing antibody responses, and with the inclusion of the Algel-IMDG adjuvant, this is the first inactivated SARS-CoV-2 vaccine that has been reported to induce a Th1-biased response. BBV152 is stored at 2–8°C, which is compatible with immunization cold-chain requirements. Both Algel-IMDG formulations were selected for the phase 2 immunogenicity trials. Further efficacy trials are warranted.'
January 17, 2021 - Bharat Biotech to pay compensation if Covaxin causes side effects. In phase 1 and phase 2 clinical trials, Covaxin has demonstrated the ability to produce antidotes against COVID- 19. However, the vaccine's clinical efficacy was yet to be established, and it was still being studied in phase 3 clinical trials, the vaccine maker said.
January 12, 2021 - Bharat Biotech announced that it had signed an agreement with Precisa Medicamentos for the supplies of COVAXIN™ to Brazil. His Excellency Ambassador of Brazil to India, André Aranha Corrêa do Lago, joined on a virtual platform. He expressed his keen interest on behalf of the Govt. of Brazil towards the procurement of COVAXIN™. In principle, it is understood between both parties that supplies of COVAXIN™ to be prioritized for the public market through a direct procurement by the Govt. of Brazil. Supplies to the private market would be based upon receipt of market authorization from ANVISA, the Brazilian regulatory authority.
January 9, 2021 - Bharat BioTech achieved the recruitment target of 25,800 on January 7, 2021, for the ongoing Phase 3 Covaxin trial.
January 8, 2021 - Immunogenicity and protective efficacy of BBV152, whole virion inactivated SARS- CoV-2 vaccine candidates in the Syrian hamster model. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection vaccinated hamsters did not show any histopathological changes in the lungs. The hamster's protection was evident by the rapid clearance of the virus from the lower respiratory tract, reduced virus load in the upper respiratory tract, absence of lung pathology, and robust humoral immune response.
January 3, 2021 - Dr. Balram Bhargava, the Director-General of the Indian Council of Medical Research, told NDTV, ''The indicators are that it has a very high efficacy,'' but declined to provide any specific detail. An efficacy report, he said, ''would be (available) within weeks.''
January 3, 2021 - India's Drugs Controller General of India on Restricted Emergency approval announced the emergency use of a coronavirus vaccine produced by local firm Bharat Biotech.
January 2, 2021 - The India Subject Expert Committee of Central Drugs Standard Control Organisation (CDSCO) has reportedly recommended Covaxin for emergency use authorization, reported news agency ANI. The CDSCO recommendation, along with rollout modalities, will now be taken up by the Drug Controller General of India for a final decision on the matter.
December 29, 2020 - Covaxin, a vaccine candidate being developed by Bharat Biotech for COVID-19, can offer protection against mutations of coronavirus, Chairman and Managing Director of the city-based vaccine maker Krishna Ella said. He also said the company had approached regulatory authorities seeking approval for an emergency license to use the vaccine, developed in collaboration with the Indian Council of Medical Research and the National Institute of Virology and now undergoing phase 3 trials.
December 22, 2020 - Pennsylvania-based Ocugen, Inc. and Bharat Biotech announced that the companies had signed a binding letter of intent to co-develop Bharat Biotech’s COVID-19 vaccine candidate, COVAXIN™, an advanced stage whole-viron inactivated vaccine candidate, for the United States market. In preparation for the development of COVAXIN™ in the US, Ocugen has assembled a Vaccine Scientific Advisory Board featuring leading academic and industry experts to evaluate the clinical and regulatory path to approval in the US market.
November 16, 2020 - Bharat Biotech has announced the commencement of Phase III trials of COVAXIN™. The Phase III trials will involve 26,000 volunteers across India, conducted in partnership with ICMR, the largest clinical trial conducted for a COVID-19 vaccine in India.
November 1, 2020 - Various media sources reported that Bharat Biotech is planning to launch its vaccine for COVID-19 in the second quarter of 2021 if it gets the requisite approvals from the Indian regulatory.
October 22, 2020 - Bharat Biotech has received the drug regulatory authority's approval to initiate the final phase of clinical trials. Phase 3 trials are likely to start in November. As many as 28,500 people are expected to enroll in India's trials.
September 28, 2020 - ViroVax LLC has licensed its adjuvant, Alhydroxiquim-II, to Bharat Biotech International Limited. Bharat Biotech is partnering with the Indian Council of Medical Research to produce India’s first COVID-19 vaccine approved for human trials, COVAXIN, which uses ViroVax’s adjuvant technology.
September 23, 2020 - Bharat Biotech announced a licensing agreement with Washington University School of Medicine in St. Louis for a novel chimp adenovirus, a single-dose intranasal vaccine for COVID-19. Bharat Biotech owns the rights to distribute the vaccine in all markets except the USA, Japan, and Europe. While the Phase I trials will take place in Saint Louis University’s Vaccine & Treatment Evaluation Unit, Bharat Biotech, upon obtaining the required regulatory approval, will pursue further stages of clinical trials in India and undertake large scale manufacture of the vaccine at its facility located in Genome Valley, Hyderabad.
August 14, 2020 - According to local media reports in India, preliminary Phase I trial results showed that the vaccine is safe, and the participants are receiving the 2nd dose. The trial’s principal investigator Dr. Savita Verma at the Post-Graduate Institute of Medical Sciences, said no adverse events were reported in subjects vaccinated at the site. Twelve medical institutes were selected to conduct Phase I/II trial, including AIIMS Delhi, Patna, Post-Graduate Institute of Medical Sciences in Rohtak, and Gillurkar Hospital and Research Institute Nagpur.
July 26, 2020 - The first part of a phase 1 study of the Covaxin human trial began on July 17, 2020. It was completed on July 25th at Post-Graduate Institute of Medical Sciences, Rohtak, said Dr. Savita Verma, principal investigator of the vaccine trial team.
July 15, 2020 - Bharat Biotech announced that the Phase-I clinical trials of India’s first indigenous COVID-19 vaccine, Covaxin began across the country, enrolling 385 people in 12 hospitals across the country.
July 13, 2020 - All India Institute of Medical Sciences in Patna, India, is set to begin human trials of India’s first coronavirus vaccine, Covaxin.
June 29, 2020 - India's Covaxin has received permission to initiate Phase I & II Human clinical trials after the company submitted results generated from preclinical studies, demonstrating safety and immune response.
May 8, 2020 - The Council of Scientific and Industrial Research (CSIR), under its flagship program NMITLI, has sanctioned a project to develop human monoclonal antibodies as therapy for COVID-19 infections. The project is being led by Bharat Biotech, a leading manufacturer of vaccines and biotherapeutics and a product supplier to over 65 countries globally.
Covaxin COVID-19 Vaccine Clinical Trial
Clinical Trial NCT04641481: An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers.
This is a phase 3 Event-Driven, randomized, double-blind, placebo-controlled, multicentre study to Evaluate the Efficacy, Safety, and Immunogenicity of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Volunteers aged 18 years and above.
A total of 25,800 subjects will be enrolled and randomized in a 1:1 ratio to receive the BBV152 vaccine and control. All participants will be assessed for efficacy and safety endpoints and provide a Nasopharyngeal(NP) swab and blood sample before the first dose of IP. The NP swab and blood collected will be subject to RT-PCR and Anti-SARS-CoV-2 IgG antibodies. The results of this will not affect the enrollment of the participant. Participants who are found to be positive for either RT-PCR Or Anti-SARS-CoV-2 IgG antibodies will be excluded from the primary efficacy analysis. A safety follow-up will be done for all.
Clinical Trial NCT04471519: Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers - last updated on October 1, 2020.
A double-blind, Multi-Centre study evaluates the safety, reactogenicity, tolerability, and immunogenicity of three investigational vaccine groups and one placebo group in healthy volunteers who receive two intramuscular doses of BBV152 vaccine formulations and placebo.
A total sample size of 755 healthy volunteers, with 375 and 380 volunteers in phase 1 and 2 studies, respectively.
Estimated Study Completion Date: June 30, 2021.