Mitsubishi's Medicago heads for Covid-19 booster queue

 With all the different variants in circulation, Covid-19 presents vaccines with a tougher challenge than in the early days of the pandemic. So headline efficacy of 71% from the phase 3 trial of Medicago’s project, announced today, feels like a respectable number.

There is a potential red flag here, however: the results released so far are on a per-protocol basis. The company insists that a “very similar” number was generated by an intent-to-treat analysis, a more rigorous test that regulators will presumably demand, and surpassed the 65% that the trial was powered to show.

Based on the number of events in each cohort, Evaluate Vantage calculates vaccine efficacy on an ITT basis as around 68%, which while less impressive still counts as a win. Meanwhile, efficacy rates against various variants, detailed in a press release and again on a per-protocol basis, also look good enough for approval – assuming that the results stand up to deeper scrutiny.

Plant power: topline results from Medicago's Covid-19 vaccine
		Covid-19 events
	Efficacy	Vaccine	Placebo
Topline analyses
Per protocol	71%	39	118
Intent to treat	68%*	40	125
Subgroups (per protocol)
Those with no prior Covid-19 exposure	75.6%
Delta variant	75.3%
Gamma variant	88.6%
Note: *calculated by Evaluate Vantage, assuming enrolment of 12,000 patients into each cohort; all other data sourced to Medicago.

Medicago, a division of Mitsubishi Tanabe, told Vantage that around 14% of patients enrolled into the study were subsequently found to have evidence of a prior infection, adding that the cases were evenly distributed between the two cohorts.

Reassuringly, no severe cases or hospitalisations were seen with the vaccine, versus three and two cases respectively in the placebo group. No deaths due to Covid-19 were recorded.

Finding a role

Medicago has already begun a rolling submission with the Canada regulator, and initiated the filing process in the US and Europe. The group’s novel technology will also be scrutinised: it uses plants to generate the virus-like particles that form the basis of the vaccine (Mitsubishi's Medicago readies for the second wave, May 28, 2021).

Glaxosmithkline’s pandemic adjuvant is being used to boost the efficacy of this vaccine, although the pharma company's involvement in this project extends no further. 

Assuming that approvals are forthcoming, capacity is a big issue: for now, Medicago has pledged 76 million doses to the Canadian government, but that will be it until a new plant, capable of making a billion shots a year, comes online in 2024.

By that time, demand in more developed countries will be based mostly around boosters, and Medicago says it is planning a trial to test its shot in this setting.

Still, while MT-2766’s ultimate role in the pandemic remains unclear, this is notable progress for this developer. And it should not be forgotten that Medicago has beaten some considerably larger vaccine players to this result.

Aiming for the booster market? the second wave of Covid-19 vaccines
Company	Project	Mechanism/technology	Status	Trial
Medicago (Mitsubishi; uses Glaxosmithkline adjuvant)	MT-2766	Plant based, virus-like particle vaccine	Topline VE 71% (Dec 2021); rolling review ongoing in Canada, filings in US, Europe and globally to follow	NCT04636697
Novavax	NVX-CoV2373	Recombinant spike protein vaccine	Topline VE 91% (Jun 2021); filed in Europe and other international markets; US filing due before YE 2021	NCT04583995
Valneva	VLA2001	Adjuvanted, inactivated virus	Succeeded in ph3 Cov-Compare vs Vaxzevria*; filed with EMA and MHRA	NCT04864561
Sanofi/ Glaxosmithkline	Unnamed vaccine	Monovalent and bivalent recombinant protein vaccines	Efficacy readout due by YE 2021	NCT04904549
Inovio/VGX Pharmaceuticals	INO-4800/ VGX-3100	DNA vaccine	Ph3 Innovate trial ongoing in S America & Asia; FDA clinical hold lifted Nov 2021; interim efficacy data due H1 2022	NCT04642638
Bavarian Nordic	ABNCoV2	Capsid virus-like particle vaccine	Pivotal trial to start in 2022, probably a non-inferiority study in booster setting vs approved mRNA vaccine	TBC
Arcturus	ARCT-021	mRNA vaccine	Ph2 fully enrolled; selected for ph3 by an unnamed "global entity"	NCT04668339
	ARCT-154	mRNA vaccine	Pivotal development ongoing in Vietnam with partner Vinbiotech, filing expected by YE 2021; ph2 US booster study results due Q1 2022	NCT05012943; NCT05037097
Vaxart	VXA-CoV2-1	Oral vaccine	Ph2 started in US Q3 2021, results due Q1 2022	NCT05067933
*No ph3 placebo-controlled study has been conducted with VLA2001. In Cov-Compare the project showed significantly higher levels of neutralising antibodies than Astra’s vaccine, and similar rates of seroconversion. Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/mitsubishis-medicago-heads-covid-19-booster-queue