COVIFENZ® COVID-19 Vaccine Description - 2022
Medicago and GSK's COVIFENZ® (CoVLP+AS03) COVID-19 vaccine uses living plants as bioreactors to produce non-infectious versions of viruses (Virus-like Particles, or VLP). VLPs mimic the architecture of a virus but are non-infectious.
The technology Proficia® uses N. benthamiana plants, the most widely used experimental host in plant virology, due mainly to many viruses that can successfully infect it. Its weakened immune system, the result of natural genetic changes over millennia, means genetic material can be successfully hosted by the plant and not rejected. The natural cell process of Nicotiana benthamiana is therefore temporarily exploited to produce VLPs.
The VLPs present antigens to the individual's immune system, eliciting a protective and long-lasting immune response. In addition, VLPs mimic the native structure of viruses, allowing them to be easily recognized by the immune system. However, they lack core genetic material, making them non-infectious and unable to replicate. In other words, they induce an immune response similar to a natural infection but without the inconveniences associated with it.
VLPs can also be engineered to have antigens attached for use in vaccines or other immunotherapies, says the company. For example, GSK and Medicago announced a collaboration on July 7, 2020, with GSK's pandemic adjuvant system. In addition, on July 8, 2020, Medicago partnered with Dynavax to test the adjuvant, Cpg 1018 (ISS-1018), which provides an enhanced immune response.
On October 7, 2021, the companies announced: 'The overall vaccine efficacy rate against all variants of SARS-COV-2 was 71% (95% Confidence Interval: CI 58.7, 80.0; Per Protocol Analysis: PP). The corresponding number for people with an initial seronegative status indicating no previous exposure to COVID-19 was 75.6% (95% CI: 64.2-83.7; PP). The vaccine candidate demonstrated the efficacy of 75.3% (95% CI: 52.8, 87.9; PP) against COVID-19 of any severity for the globally dominant Delta variant. Efficacy was 88.6% (95% CI: 74.6, 95.6; PP) against the Gamma variant. No Alpha, Lambda, and Mu variants were observed in the vaccinated group, while 12 cases were observed in the placebo group. The Omicron variant was not circulating during the study.
GSK confirmed on February 9, 2022, that data from the Phase III trial of their plant-based COVID-19 vaccine candidate, combined with GSK's pandemic adjuvant, demonstrated 71% efficacy against the main variants SARS-COV-2 circulating at the time of the trial. And announced with Sanofi that a single booster dose of the recombinant, adjuvanted COVID-19 vaccine candidate was well tolerated and delivered strong immune responses regardless of the primary vaccine received.
On February 24, 2022, Medicago and GSK announced that Health Canada had approved COVIFENZ®. Health Canada based its decision on scientific data shared by Medicago as part of their rolling submission that began in April 2021 under an Interim Order and concluded with the filing of a New Drug Submission-CV.
Canadian media reported on March 25, 2022, “We are aware that the WHO updated Medicago’s vaccine status to ‘not accepted.’ We received an email that indicated the WHO’s preliminary decision and informed us that official communication outlining the details and rationale would follow,” wrote Medicago President and CEO Takashi Nagao in a statement to Global News. “Once we receive this, we will review the rationale and continue to discuss the next steps with our partners and shareholders.”
The peer-review journal NEJM published an Original Article on May 4, 2022, that a phase 2/3 clinical study found the CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease.
U.K.-based GSK collaborates with companies and research groups worldwide, working on promising COVID-19 vaccine candidates using our innovative vaccine adjuvant technology.
Located in Quebec City, Canada, Medicago is a biopharmaceutical company and pioneer in plant-based therapeutics technology. It was founded in 1999 with the belief that innovative approaches and rigorous research would bring new solutions to healthcare. Medicago is an affiliated company of Mitsubishi Tanabe Pharma Corporation (MTPC) Group, with its headquarters in Osaka, Japan. MTPC is a member of Mitsubishi Chemical Holdings Group.
The Covifenz CoVLP vaccine is indicated to prevent COVID-19 disease caused by the SARS-CoV-2 virus. However, no pediatric vaccine efficacy has been disclosed.
Subjects in a phase 3 study received two doses of 3.75 µg of Covifenz CoVLP adjuvanted with AS03 adjuvant given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once).
In a phase 2 study, Covifenz CoVLP with AS03 induced a greater humoral response in Adults than in Older Adults after a single dose. Still, this effect was overcome with a second dose when both age cohorts responded with NAb titers ∼10-fold higher than those in a panel of sera from patients recovering from COVID-19. A single dose of CoVLP with AS03 induced a significant IFN-γ response in both age cohorts; a second dose significantly boosted IFN-γ and IL-4 responses in both age cohorts. Adults generated a stronger IFN-γ and IL-4 cellular response than older adults after one or two doses of AS03-adjuvanted CoVLP.
COVIFENZ Side Effects
During the Covifenz phase 3 study, no related serious adverse events were reported. To date (Dec. 7, 2021), the Phase 3 results have confirmed the safety profile is consistent with Phase 2 results. In addition, the frequency of mild fever was low (<10%), even after the second dose.
Health Canada issued authorization for COVIFENZ® on February 24, 2022. COVIFENZ is not currently approved or authorized to prevent COVID-19 or any indication anywhere other than Canada.
COVIFENZ News For 2020 - 2022
June 8, 2022 - The New England Journal of Medicine has published results of Phase 3 studies for two novel Covid-19 vaccine platforms.
May 5, 2022 - Medicago announced the publication of the results from the Phase 3 study of COVIFENZ by the NEJM. “The world needs a diverse range of vaccine options to continue to fight COVID-19, and we are proud to be able to contribute”, said Toshifumi Tada, CEO, and President at Medicago.
March 25, 2022 - The World Health Organization has decided not to accept the Medicago COVID-19 vaccine for emergency use, citing the company's ties to big tobacco. Marlboro cigarette manufacturer, Philip Morris International, is a shareholder of the Quebec City-based company.
February 25, 2022 - The Government of Canada contracted with Medicago to supply the COVID-19 vaccine and is committed to fulfilling this order as soon as possible. "The approval of our (Covifenz) COVID-19 vaccine is a significant milestone for Canada in the fight against the pandemic. We appreciate Health Canada's timely review," said Takashi Nagao, President, and CEO at Medicago.
December 7, 2021 - Medicago and GlaxoSmithKline reported positive Phase 3 results for their plant-based COVID-19 vaccine. The overall vaccine efficacy rate against all (non-Omicron) variants of SARS-COV-2 was 75.3%.
December 7, 2021 - NPR reported A COVID vaccine grown in plants measures up.
October 1, 2021 - Medicago and GSK announced that Phase 1/2 clinical trials would begin in Japan for Medicago's plant-derived VLP COVID-19 vaccine candidate combined with GSK's pandemic adjuvant. This study will be conducted by Mitsubishi Tanabe Pharma Corporation, the parent company of Medicago. This Japanese study, combined with final data from the global Phase 2/3 study of the vaccine candidate, will support an application for regulatory approval in Japan by March of 2022.
May 18, 2021 - Medicago and GlaxoSmithKline reported positive interim Phase 2 clinical trial safety and immunogenicity data for Medicago's plant-derived COVID-19 vaccine candidate, tested in combination with GSK's pandemic adjuvant. As measured by the neutralizing antibody titer, immunogenicity was high - about ten times higher than those in a panel of sera from patients recovering from COVID-19. In addition, no related severe adverse events were reported, and reactogenicity was generally mild to moderate and short in duration.
May 17, 2021 - A non-peer-reviewed study was published: Interim Report of Phase 2 Randomized Trial of a Plant-Produced Virus-Like Particle Vaccine for Covid-19 in Healthy Adults Aged 18-64, older Adults Aged 65 and Older.
April 23, 2021 - Medicago announced that Health Canada received for review the first portion of Medicago's plant-derived adjuvanted COVID-19 vaccine candidate rolling submission on April 19.
March 16, 2021 - Medicago and GlaxoSmithKline announced Phase 3 clinical testing of Medicago's plant-derived COVID-19 vaccine candidate combined with GSK's pandemic adjuvant part of the ongoing Phase 2/3 study. In addition, Medicago received approval from Canadian and US regulatory authorities to enroll healthy adults in the Phase 3 portion of the trial based on positive interim Phase 2 results. Medicago has also initiated a vaccine candidate's feasibility study to address the emerging COVID-19 variants.
February 17, 2021 - The vaccine candidate, combined with the pandemic adjuvant, was granted Fast Track designation by the U.S. FDA which allows the FDA to expedite the development and review of new medicines and vaccines intended to treat or prevent serious conditions and address an unmet medical need.
November 12, 2020 - Medicago and GSK announce the start of Phase 2/3 clinical trials of its plant-derived vaccine candidate for COVID-19 to evaluate its efficacy, safety, and immunogenicity. Based on the positive Phase 1 results and the approval of Canadian regulatory authorities, Medicago has decided to launch the Phase 2/3 clinical trial with GSK's pandemic adjuvant.
November 10, 2020 - A study found that 100% of subjects who received an adjuvanted vaccine candidate developed significant antibody and cellular immune responses after two doses.
November 6, 2020 - Non-peer-reviewed study: Phase 1 trial of a Candidate Recombinant Virus-Like Particle Vaccine for Covid-19 Disease Produced in Plants. Conclusion CoVLP ± adjuvants were well-tolerated. Several adjuvanted formulations elicited strong humoral and T cell responses after dose 2. Even at the lowest CoVLP+AS03 dose, NtAb titers were ∼10-times higher than convalescent serum with a balanced IFNγ and IL-4 response. These findings support the transition of CoVLP (3.75μg+AS03) to further clinical evaluation.
October 23, 2020 - Medicago announced that it had reached an agreement to supply Canada's Government with up to 76 million doses of its vaccine against COVID-19, subject to Health Canada approval. Medicago will also receive $173M in funding support from the Government of Canada for its vaccine research and development and the construction of its Quebec City manufacturing facility.
July 14, 2020 - Medicago began Phase I clinical trials for its plant-derived COVID-19 vaccine candidate yesterday, administering the first doses in healthy human volunteers. Medicago is also planning a Phase 2/3 trial in October 2020.
July 8, 2020 - Dynavax Technologies Corporation and Medicago, a biopharmaceutical company creating vaccines and therapeutics by leveraging innovative plant-based technologies, announced their collaboration to investigate an adjuvanted vaccine candidate to protect against COVID-19. The collaboration evaluates the combination of Medicago's Coronavirus Virus-Like Particle (CoVLP) with Dynavax's advanced adjuvant, CpG 1018™. Adding CpG 1018, the adjuvant in Dynavax's U.S. FDA-approved adult hepatitis B vaccine, is intended to enhance the immune response of Medicago's COVID-19 vaccine to decrease the total amount of antigen needed per dose, providing more doses to help protect a greater number of people.
March 12, 2020 - Medicago said it had produced a virus-like particle of the novel coronavirus, a first step towards producing a vaccine, which will now undergo pre-clinical testing for safety and efficacy.
Medicago COVIFENZ COVID-19 Vaccine Clinical Trials
In clinical trials, Medicago and GSK tested their CoVLP adjuvanted recombinant COVID-19 plant-derived vaccine candidate. The Phase 3 study is an event-driven, randomized, observer-blinded, crossover placebo-controlled design that will evaluate the efficacy and safety of the CoVLP formulation, compared to placebo, in up to 30,000 subjects in North America, Latin America, Japan, and Europe.
Other clinical trials are listed on this webpage.