Medicago and GSK announce positive phase III efficacy and safety results for adjuvanted plant-based COVID-19 vaccine candidate.

Vaccine efficacy was demonstrated in an environment dominated by SARS-CoV-2 variants, unlike most published Phase III efficacy trials for currently licensed COVID-19 vaccines that were conducted when only the ancestral virus was circulating, making direct comparisons impossible. The overall vaccine efficacy rate against all variants of SARS-COV-2 was 71% (95% 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 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. Although only a small number of severe cases occurred in this study, none occurred in the vaccinated group. No cases of the 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. During the study, no related serious adverse events were reported and reactogenicity was generally mild to moderate and transient; symptoms lasting on average only one to three days. To date, the Phase III results have confirmed the safety profile is consistent with Phase II results. The frequency of mild fever was low ( less than 10%), even after the second dose. Full results of the Phase III study will be released in a peer-reviewed publication as soon as possible.

Based on these results, Medicago will imminently seek regulatory approval from Health Canada as part of its rolling submission. The vaccine candidate is not yet approved by any regulatory authority.

If approved, the companies will be contributing to the world’s fight against the COVID-19 pandemic with the world’s first plant-based vaccine for use in humans,” said Takashi Nagao, CEO and President at Medicago.

Medicago has been developing its plant-based technology for the past 20 years, using unique technology to produce Virus-Like Particles (VLP) for its protein vaccines. VLPs are designed to mimic the native structure of viruses, allowing them to be easily recognised by the immune system. Because the VLPs lack core genetic material, they are non-infectious and unable to replicate. VLP vaccines developed by other technologies have traditionally been used worldwide for more than 30 years.

About the Phase II/III study: The Phase II/III study has a multi-portion design to confirm that the chosen formulation and dosing regimen of the vaccine candidate (two doses of 3.75 µg of antigen combined with GSK's pandemic adjuvant given 21 days apart) has an acceptable vaccine profile in healthy adults 18-64 years of age, elderly subjects aged 65 and over and adults with comorbidities. The Phase II portion of the trial was a randomized, observer-blind, placebo-controlled study to evaluate the safety and immunogenicity of the adjuvanted recombinant COVID-19 plant-based vaccine candidate in subjects aged 18 and above. It was conducted in multiples sites in Canada and the United States in a population composed of healthy adults (18-64y), elderly adults (over 65y) and adults with comorbidities. Each age group enrolled up to 306 subjects randomized 5:1 to receive the adjuvanted vaccine candidate: placebo and with 2:1 stratification in older adults (65-74 and greater than 75). All subjects are being followed for a period of 12 months after the last vaccination for assessment of safety and the durability of the immune responses which will be the final analysis.

The Phase III portion of the trial was launched in March 2021 and was an event-driven, randomized, observer-blinded, crossover placebo-controlled design that evaluated the efficacy and safety of the vaccine candidate formulation, compared to placebo, in over 24,000 subjects across Canada, the United States, United Kingdom, Mexico, Argentina, and Brazil.

The data communicated are Per-Protocol, meaning only data from participants who followed the protocol throughout the study are included. A parallel Intention to Treat (ITT) analysis that considers the treatment received by all participants, without regard to protocol adherence yielded very similar results.

The vaccination regimen calls for two doses (3.75 microgram of antigen in combination with GSK’s pandemic adjuvant) given intramuscularly 21 days apart. The vaccine is stored at 2 °C to 8 °C, enabling the use of traditional vaccine supply and cold chain channels.