Medicago’s tech takes the idea of traditional vaccine manufacturing – based on using eggs to produce viruses – and instead uses living plants as the bioreactor that produces a protein particle that mimics the target virus.
Covifenz represents the first COVID-19 vaccine using plant-based vaccine; as well as being Medicago’s first approved vaccine and the first authorized COVID-19 vaccine developed by a Canadian-based company.
Founded in 1999, Quebec City’s Medicago is a pioneer of plant-derived therapeutics. Its research started with an influenza vaccine candidate but pivoted to COVID-19 at the start of the pandemic. In 2013 Mitsubishi Tanabe Pharma Corporation (MTPC) Group became the majority parent company: with the Japanese giant positioning vaccines and new modalities as one of its key R&D areas.
The recombinant, adjuvanted vaccine is indicated in Canada for active immunization to prevent coronavirus disease 2019 (COVID‑19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) in individuals 18 to 64 years of age.
Covifenz uses Coronavirus-Like Particle (CoVLP) technology with the vaccine composed of recombinant spike (S) glycoprotein expressed as virus-like particles (VLPs) co-administered with GSK’s pandemic adjuvant. The vaccination regimen calls for two doses given intramuscularly 21 days apart (3.75 micrograms of CoVLP antigen in combination with GSK pandemic adjuvant in the same injection). The vaccine is refrigerator-stable.
Phase 3 efficacy and safety result, published by the companies in December, demonstrated 75.3% efficacy against COVID-19 of any severity caused by the Delta variant.
The Omicron variant was not circulating during the study: but the companies are now assessing the vaccine’s efficacy against variants, Brian Ward, Medicago’s Medical Officer, told this publication. “In the coming weeks, as part of our clinical development strategy, we will begin a booster study to determine the effectiveness of a booster dose against evolving variants. We are measuring the immune responses induced by the vaccine against the Omicron variant in clinical samples from participants in our clinical studies.”
Looking forward, the regulatory filing process for the vaccine has been initiated in the US with the FDA; and preliminary discussions are underway with the WHO for preparation of a submission. A Phase 1/2 trial has been initiated in Japan where Medicago plans to submit for regulatory approval in combination with the Phase 2/3 global study results in the spring.
Transforming a company from R&D to commercial production
Covifenz joins five other COVID-19 vaccines in Canada: Moderna and Pfizer/BioNTech’s mRNA vaccines; AstraZeneca and J&J’s viral vector vaccines; and – as of February 17 – Novavax’s COVID-19 vaccine.
The approval of Canada’s first home-grown COVID-19 vaccine has been welcomed by the government, which is eying up an opportunity to growth the country’s biomanufacturing sector.
“As one of our government’s top priorities has been to reverse the 40-year decline faced by Canada’s biomanufacturing sector, we are pleased to see Medicago’s vaccine approval,'" said the Honourable François-Philippe Champagne, Minister of Innovation, Science and Industry. "It is a great milestone for Canada’s biotechnology sector and for homegrown innovation. We will continue to support companies that want to produce vaccines in Canada and join the growing national biomanufacturing sector.”
Manufacturing plant-based vaccines
The first step is to create the required protein particle and introduce it into a plant-specific bacterial vector. This is then taken up by plants which multiplies the vector. It takes just a matter of days for the ‘mini-factories’ to produce the Virus-Like-Particles (VLPs) – compared to around six months for egg-based production (The company highlights that plants are not genetically modified; rather, the plants’ natural cellular processes are used).
The VLPs are then extracted and purified to produce the final material for the vaccine.
In October 2020, Medicago received $173m in funding support for its vaccine research and development, and for the construction of its Quebec City manufacturing facility; with the government agreeing an order for up to 76 million doses. It has also received support from the Government of Quebec.
Medicago is now working on its initial delivery to the Canadian government, which will include 20 million doses in 2022.
The vaccine will be manufactured between Canada and the US: with sites in Durham, North Carolina; and Quebec, Canada.
“As Medicago transforms from a research and development organization to a large-scale manufacturing one, we are putting all our efforts in scaling our manufacturing accordingly,” said Ward.
“Manufacturing vaccines is a complex journey, it follows a rigorous process and quality controls. It requires know-how, expertise, and passion for quality. We received the NOC from Health Canada on February 24, 2022 and we have several steps to go through before we can deliver our vaccine. This process will take weeks.”