China’s Biggest Covid Failure Is Not Deploying an mRNA Vaccine

(Bloomberg Businessweek) -- Weeks into a Covid-19 outbreak in Shanghai that brought China's financial hub to a standstill, the government of President Xi Jinping has demonstrated its willing to go to extremes in its quest to contain the virus. One thing Xi has so far been unwilling to do is deploy a powerful tool against the highly contagious omicron variant: mRNA vaccines. Those shots could reduce the chances of elderly and other vulnerable Chinese getting seriously ill or dying—and possibly help the country transition away from its “Covid Zero” stance.

Lining up the necessary supplies shouldn't be hard because Shanghai Fosun Pharmaceutical Group Co. in March 2020 agreed to buy a stake of 0.7% in BioNTech SE and to market the mRNA vaccine the German company co-developed with Pfizer Inc. in China. Before the close of that same year, the two companies had arrived at a plan to distribute 100 million doses in China, once they got the green light from the government. Yet the drug regulator has yet to grant approval.

“Worldwide data clearly indicates mRNA is the gold standard,” says Joerg Wuttke, president of the European Union Chamber of Commerce in China, which wrote to the Chinese government in April urging it to allow the shots. “Why waste time and wait, for what?”

The wait, many analysts believe, is for a local company to come up with its own mRNA vaccine. Since the start of the pandemic, Xi's government has touted self-reliance in fighting Covid, promoting domestic vaccines based on inactivated versions of the virus and barring all foreign ones from the market. Slightly more than 88% of China's 1.4 billion people have received two doses of those shots.

Opening up to foreign-made mRNA shots risks embarrassing Xi and other officials, says Allison Hills, senior consultant in London with Eradigm Consulting, which advises biotech and pharmaceutical clients. “For them to say now we are accepting BioNTech,” she says, “it's tantamount to saying ours are not as good.”

Clinical trials have shown the inactivated vaccines from China's Sinopharm Group Co. and Sinovac Biotech Ltd. to be less effective in stopping infections, though the gap in protecting against severe disease and death is narrower.

Last year, optimists hoped China's go-it-alone strategy would lead to the speedy approval of a locally made mRNA vaccine, co-developed by Walvax Biotechnology Co., Suzhou Abogen Bioscience Co., and the Academy of Military Medical Sciences. Upbeat about their chances, the partners invested in a new facility to ramp up production once Beijing gave the green light, with state media reporting production would start by August 2021. However, results of early trials were disappointing and the vaccine is unlikely to reach the market before the end of 2022, according to Bloomberg Intelligence.

One reason for the delay could be the different approach the Walvax group took. Unlike the shots from Pfizer-BioNTech and Moderna Inc., the Chinese vaccine targets a part of the coronavirus spike protein that binds to cells in the body, according to Sam Fazeli, senior pharmaceutical analyst with Bloomberg Intelligence in London. For vaccine developers, focusing on this smaller area, called the receptor binding domain, can reduce costs and may facilitate manufacturing. It can also add uncertainty, given that this particular domain is a focal point for mutations in newer variants.

“Walvax's problem is the majority of the mutations with omicron are in that receptor binding domain,” says Fazeli. “The risk is that their vaccine's efficacy is likely to be much more compromised compared to other vaccines.”

Walvax, which didn't respond to a request for comment regarding the design of the mRNA vaccine it co-developed with Abogen, says it has partnered with a Shanghai-based biotech startup called RNACure Biopharma to develop another mRNA vaccine targeting variants, including omicron. This one encodes a full-length spike protein that covers major mutations from variants. The companies are seeking approvals to begin human testing.

Walvax's difficulties have raised the stakes for other Chinese companies working on vaccines using the same technology. In early April, China gave permission for CanSino Biologics Inc. and CSPC Pharmaceutical Group Ltd. to each begin first-phase trials for their mRNA shots.

Other drugmakers are further along: Shanghai-based Stemirna Therapeutics Co. has tested an mRNA candidate in Laos and plans further testing in Brazil. It hopes to get emergency-use approval in Southeast Asia and South America. Beijing-based AIM Vaccine Co., which has a Phase 2 trial of its mRNA vaccine under way in China, expects to apply for conditional approval by the end of the year, according to spokesperson Lingna Ding.

Early data from Hong Kong's winter omicron wave show why mRNA vaccines could be valuable in China. A preprint study by researchers at the University of Hong Kong in late March concluded that two doses of the Sinovac vaccine underperformed BioNTech's shots, especially among the elderly. For prevention of severe disease, BioNTech's vaccine effectiveness in people 80 and older was 84.5%, compared with just 60.2% for Sinovac; for protection against death, there was a gap of about 20 percentage points, with BioNTech at 88.2% and Sinovac at 66.8%.

The study, which was funded by the Chinese government, found no significant gap for those who had received three doses. That cohort, however, was small, as only about 10% of seniors had received boosters and government vaccination teams dispatched to nursing homes—sites of the worst outbreaks—only offered Sinovac shots.

Another study by Hong Kong researchers, published in January in the journal Nature, concluded that governments primarily using Sinovac's vaccines should consider mRNA vaccine boosters in response to the spread of omicron.

Given the strong performance of mRNA vaccines, providing them as boosters should help people who have received two doses of Chinese shots, says Jyoti Somani, senior consultant for the Division of Infectious Diseases at National University Hospital in Singapore, where the government has approved China's inactivated-virus vaccines as well as mRNA shots developed elsewhere. “It looks like you are getting a much broader immune response when you mix and match,” she says. “What is clear is that we need both.”

That argument is winning support inside China. Zhong Nanshan, a pulmonologist and influential government adviser on Covid, in March co-authored a road map for China's reopening that identified better booster coverage, with different vaccine types, as essential. Ding Sheng, dean of Tsinghua University's School of Pharmaceutical Sciences, in March said that existing Chinese vaccines weren't protective enough against omicron and that the government should encourage companies to introduce more effective shots.

Fosun's chief executive officer, Wu Yifang, told reporters at a briefing on March 23 that China's drug regulator is still weighing whether to approve the BioNTech shot. Authorities in February gave the green light to Pfizer's antiviral treatment, Paxlovid, filling a need because Chinese drugmakers don't have any antivirals of their own. In the same way, regulators might eventually lose patience with Chinese vaccine makers and open the door to BioNTech's shots.

With no mRNA vaccines of any kind on the horizon, Chinese health officials may have to focus on better deploying the shots now available, targeting vaccine holdouts, especially among seniors, and improving booster rates. Approximately half the population has received booster shots. That compares with about 30% in the U.S. “Any of the vaccines would be a good thing,” says Colin Pouton, a professor at the Monash Institute of Pharmaceutical Sciences in Melbourne.

The Covid Zero policy is making that more difficult, with millions of residents stuck in their homes in Shanghai and other cities. “We have economic damage, we have social tension, we have basically a whack-a-mole outlook,” says Wuttke. “Two years have passed and China has no mRNA vaccines to offer.” —Bruce Einhorn