One of the world’s fastest-moving efforts to develop a COVID-19 vaccine is falling behind rivals, its advance appearing to be stymied by political tensions between China and Canada, and concerns that its shot might not work as well as others.
CanSino Biologics, the Chinese company that in March started the world’s first human tests on an experimental coronavirus shot, has yet to start administering shots in critical final-stage trials on the vaccine that it developed with the Chinese military.
Rivals such as US-based Moderna, Britain’s AstraZeneca, and China’s Sinovac Biotech and Sinopharm are well into this last phase of testing, giving test inoculations to thousands of people to find out if they work.
Illustration: Mountain People
With its progress toward phase 3 trials trailing major competitors, CanSino has not had the opportunity to assuage concerns from earlier-stage data, which showed that the immune response generated by its shot varied greatly among participants.
Its setbacks offer a look at both the scientific and political uncertainty that companies are battling as they race to produce a vaccine against the virus that has killed more than 863,000 people worldwide.
Just a few months ago, the Tianjin-based biotechnology firm was positioned at the vanguard of global vaccine trials thanks to a partnership with the Canadian government’s main research agency, which permitted the company to conduct tests in the North American country.
CanSino was supposed to send its vaccine candidate — Ad5-nCoV, developed with Canadian technology — to Canada so that final-stage tests could begin there as early as in the fall. The vials never arrived.
The Chinese General Administration of Customs has not approved shipments of CanSino’s vaccine to Canada, the National Research Council of Canada said in an e-mail on Wednesday last week.
The development appears to be part of a pattern of retribution against Canada because it arrested Huawei Technologies Co chief financial officer Meng Wanzhou (孟晚舟) on a US handover request in December 2018. Over the past few months, relations between the two countries have only worsened.
Blocking CanSino’s vaccine from leaving for Canada is clearly not just a bureaucratic glitch, because the company appears to have shipped to countries friendly to China, said Guy Saint-Jacques, a former Canadian ambassador to China.
“This is part of China’s COVID-19 diplomacy,” he said. “It’s unfortunately part of the overall difficulties we’re having with China.”
GLOBAL TIES
For CanSino, international collaboration is vital because late-stage trials require large-scale testing in a place where there is an active outbreak, something no longer possible inside China, which has largely stamped out local transmission.
With Canada as a trial site now in question, the company has had to look elsewhere.
After telling the Hong Kong Stock Exchange that it had not started enrolling participants for phase 3 trials as of Aug. 18, CanSino said in a statement on Wednesday last week that it has entered into an agreement with NPO Petrovax Pharm to conduct a trial in Russia.
CanSino declined to comment further when contacted for this story.
Petrovax told Bloomberg at the end of last month that it plans to recruit 625 volunteers in eight medical institutions in Russia, and that the selection and vaccination of volunteers would be carried out by the end of this month.
CanSino said that it and Petrovax have received approval for phase 3 clinical trials.
Since Meng’s arrest, China has jailed two Canadians on espionage charges, halted billions of dollars in Canadian imports and put four other Canadians on death row. Further denting relations between Beijing and Ottawa, Canada suspended its extradition treaty with Hong Kong in response to new security legislation imposed there by China.
The Chinese General Administration of Customs did not respond to a request for comment.
The National Research Council of Canada said in its e-mail that the partnership between CanSino and Canada was reviewed by the Chinese government, but that after it was signed, Beijing introduced changes regarding the export of vaccines.
Canada was ready to begin preliminary trials in June, but due to the delay, the research council is turning its focus to other partners, it said.
Canadian Prime Minister Justin Trudeau described the developments on the CanSino vaccine as “unfortunate.”
After hitting an all-time high of HK$271.4 on July 31, CanSino’s stock went on a steady decline last month, shedding nearly 40 percent, as news emerged that the vials it was supposed to ship to Canada for trial never left China.
On Wednesday, the stock fell as much as 11 percent before paring losses after CanSino’s statement on the Russia trial. It is still up more than 150 percent since the beginning of this year.
CanSino has had other struggles. With most of the vaccine front-runners having published their early human testing data, there have been some concerns that the antibodies triggered by CanSino’s shot as part of a vaccine-induced immune response could be lackluster compared with those stimulated by rivals, US-based Loncar Investments CEO Brad Loncar said.
That could be why the company has appeared slow in striking deals with countries to run phase 3 trials, said Loncar, who has holdings in the Chinese vaccine developer.
“Of all the data that I’ve seen of companies that have published human stage data, I would say CanSino was one that I would be most nervous about the phase 3,” Loncar said. “The antibody levels in general, when you compare them to what other companies have put out there, like Moderna, Pfizer and BioNTech, and even from the other Chinese vaccine makers like Sinovac and Sinopharm, I just think that the data hasn’t validated CanSino’s position as a front-runner.”
While analysts have noted the varying standards used in measuring vaccine-induced immune response by different groups, CanSino suffers from the challenge that its vaccine uses a genetically engineered human adenovirus, which causes the common cold and to which a lot of people already have immunity.
That pre-existing immunity has been shown to blunt the vaccine’s ability to generate the kind of antibodies that can bind to the spikes on the surface of the coronavirus to prevent it from entering human cells.
RIVAL TRIALS
Other Chinese vaccine makers are further ahead on phase 3 trials.
Beijing-based Sinovac has started vaccinating people in Brazil and Indonesia, while more countries are signing up to be part of the company’s multi-center late-stage tests.
State-owned China National Biotec Group is testing the two candidate vaccines that it developed in the United Arab Emirates, and has secured approval for further testing in Peru, Argentina and Morocco.
CanSino, in addition to the delayed Canada trial and its agreement with Russia, is talking to Brazil, Chile and Saudi Arabia on final-stage testing, one of the company’s founders, Qiu Dongxu (邱東旭), told a forum in July.
A large scale phase 3 seeking to enroll 40,000 people is planned for Pakistan, an online clinical trials database showed. The trial has not yet started and is to be headed by researchers from both the Chinese Center for Disease Control and Prevention and the Canadian Center for Vaccinology.
CanSino’s vaccine still warrants further testing as it is not yet known how strong an immune response the vaccine can shore up if it is administered twice, a strategy that has been tested by almost all front-runners except for CanSino. Trials in Canada could potentially find out the effect of a booster shot — if the vials ever make it to Canadian shores.
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