(July 21): Shionogi & Co’s experimental Covid-19 treatment Xocova failed to win the backing of health experts in Japan who said there wasn’t enough data to show the medicine’s efficacy.
The panel members didn’t recommend that Japan’s health ministry authorise emergency use of the therapy as there was a need to continue discussion on it, Hiroshi Kiyota, chairman of the expert committee said in a briefing Wednesday. The health ministry relies on the panel’s decision to give the approval.
Shionogi plummeted as much as 10% in Tokyo trading, the biggest intraday drop since June 23, while shares of Shionogi’s South Korean partner, Il Dong Pharmaceutical Co, fell as much as 30% in Seoul.
Japan so far has two pills to fight coronavirus and Shionogi’s therapy was seeking to be the third option. Approval for Shionogi’s medicine was keenly watched as it is easier to take than the two currently available drugs from US drugmakers. A course of Shionogi treatment consists of seven pills over five days — significantly fewer than Pfizer Inc’s Paxlovid and Merck & Co’s Lagevrio, which require between 30 pills and 40 pills over the same time period.
The panel decided that it will continue discussion on Xocova and await submission of Phase 3 trial data which is expected in November, according to a representative from Pharmaceutical and Medical Devices Agency, Japan’s drug regulator.
This stretches the wait for a domestic supply of an antiviral medicine in Japan that can help avert hospitalisations and deaths from Covid-19. Covid pills are becoming a crucial disease-fighting tool as the world transitions to living with the virus. Japan, already one of the oldest nations in the world, has also achieved one of the lowest death rates of the pandemic.
Second review
This was Xocova’s second panel review, as required for full transparency under the existing rules for the emergency authorisation process, according to Japan’s health minister Shigeyuki Goto. The company’s shares fell 5.6% after the first meeting in June which had a similar outcome when experts postponed their decision and said additional “careful discussion” was needed.
Japan’s government agreed in March to buy 1 million courses of the drug immediately after approval. The Osaka-based company, which already can make enough to treat one million people annually, says it plans to eventually produce enough supply for 10 million patients a year.
Shionogi’s easier-to-take pill has the potential to generate US$2 billion in annual sales, Chief Executive Officer Isao Teshirogi said in October. The company partnered with the AIDS Clinical Trial Group in March to run studies needed to get US approval.
The medicine is a protease inhibitor that works like Pfizer’s Paxlovid, and targets a different part of the virus replication process than Merck’s Lagevrio. It’s possible it could be given in combination with Merck’s treatment, something the companies have discussed, Teshirogi said.
The drugmaker is also seeking opportunities to sell the medicine in other parts of the world. It’s running a phase three trial in the US with the AIDS Clinical Trials Group, and has begun submitting data to regulators in China with its partner Ping An Life Insurance Company of China Ltd.
SEP 30, 2021, 6:33 AM SGT (This article is 8 mths old)
Many governments that once relied on Chinese shots are now ordering or seeking donations of mRNA vaccines instead.PHOTO: AFP
BEIJING (BLOOMBERG) - In the early days of the Covid-19 vaccine rollout, Chinese shots saved countless lives. They kick-started inoculation programmes across Asia, Latin America and the Middle East, while richer countries hoarded scarce mRNA shots from Pfizer and Moderna.
But many governments that once relied on vaccines from Sinovac Biotech or Sinopharm Group are now turning to options from the United States and Europe instead, as concerns mount about Chinese vaccines' efficacy against the Delta strain and the Western stranglehold on mRNA supplies grows looser.
That preference may already be showing up in China's customs data, where exports of human vaccines dropped 21 per cent in August to US$1.96 billion from US$2.48 billion in July, after rising steadily since December 2020.
"Basically people took what they could get" when Covid-19 vaccines first became available, said Nicholas Thomas, an associate professor at the City University of Hong Kong who has edited several books on foreign policy and public health.
"But as this has gone on, general populations - rather than just medical practitioners - have become more educated about the differences," he said. "They have realised that not all vaccines are equal in terms of protection."
This shift played out during Thailand's deadly outbreak earlier this year. As cases surged and South-east Asia emerged as the new epicentre of the pandemic, the nation desperately tried to purchase vaccines. Only one supplier came through in time: China's Sinovac.
The shots allowed the country of 70 million to begin its inoculation campaign earlier than hoped, but Thailand soon confronted a challenge now faced by lawmakers across the developing world.
The efficacy of China's inactivated vaccines ranges from about 50 per cent to 80 per cent in clinical trials. But they are less potent than mRNA vaccines and questions are mounting about their effectiveness against the highly transmissible Delta variant.
But many Thais soon expressed a strong preference for Western shots - even protesting to demand them - and the country's opposition began lambasting the government for its reliance on China. Thailand halted orders of Sinovac and began buying more Western vaccines.
I'm not anti-Sinovac," said Chaowat Sittisak, a 29-year-old teacher in northern Thailand who got a first dose of Sinovac but ordered a second Moderna shot from a private hospital. "If the world only had one vaccine and it's Sinovac, I'd get it. But we have so many other choices. And I want whatever is best."
Many governments that once relied on Chinese shots are now ordering or seeking donations of mRNA vaccines instead. The swing away from China is likely to accelerate as US President Joe Biden promises to donate 1.1 billion mRNA shots, Europe pledges hundreds of millions of vaccines and India prepares to once again export AstraZeneca vaccines after curtailing shipments following its deadly second wave.
In addition to availability and efficacy, freedom of movement may also be motivating the shift: Recipients of Chinese vaccines cannot travel to some locations.
Vaccine exports
In a written reply to Bloomberg, Sinovac said its CoronaVac shot has been effective at preventing hospitalisation, intensive care admissions and deaths throughout the pandemic.
A spokesperson said some countries first rolled out Sinovac to the elderly, who are more likely to be hospitalised with Covid-19, while younger populations received different vaccines later, "and this should be factored in the evaluation of CoronaVac's effectiveness".
Many countries, including Thailand, have "purchased vaccines from multiple suppliers in order to maximise the number of doses available for their population," the company said.
As things stand, the list of places shifting away from Chinese vaccines - or augmenting them with Western boosters - includes Turkey and the United Arab Emirates. In China's own territory of Hong Kong, which has long offered residents a choice between BioNTech and Sinovac, health officials are now testing whether the Chinese shot will perform better when paired with a western booster.
While Sinovac allowed Thailand to start its rollout earlier than planned, the 6 million doses arriving in October will be the last shipment. In 2022, at least three quarters of the government's orders will also come from Astra and Pfizer.
Moves like Thailand's represent a blow to China's vaccine diplomacy ambitions. Nevertheless, governments face a tricky balance between wanting to protect the public and maintaining good relations with China.
The Thai Health Ministry has been careful to say that while it has no plans to order more Sinovac, it is not suggesting the shots are not effective. Chinese firms have exported some 884 million doses of its homegrown vaccines via mostly bilateral deals with places like Brazil and Indonesia.
This week, Chile started giving Sinovac shots to children as young as six, a strong endorsement of a shot that's formed the backbone of their rollout.
And there are still many parts of the world drastically short of vaccines. Some African nations, for instance, have barely started their inoculation drives after struggling to procure shots.
Cote d'Ivoire, Burkina Faso and Kenya are all rolling out Chinese vacciness, and Beijing is a key supplier to the World Health Organisation-backed Covax facility aimed at getting vaccines to the developing world. President Xi Jinping has pledged to export 2 billion doses this year, matching commitments by Group of Seven nations.
Various studies conducted around the world have shown the jabs to be effective at preventing serious illness and death. Yet China's pharmaceutical firms - which were initially less forthcoming than western companies in releasing clinical trial data - have not released similarly conclusive studies that inactivated vaccines are effective against the Delta.
Over the coming year, policymakers may well continue turning away from the older technology of the inactivated Chinese vaccines, says Benjamin Cowling, a professor of epidemiology and biostatistics at the University of Hong Kong, who published a recent study in the Lancet showing the Pfizer vaccine generated 10 times more antibodies than Sinovac.
"If you've got some vaccines that are more effective than others, and the cost is roughly the same, then you're going to get a better bang for the buck if you choose the more effective vaccines," Cowling said. "But I still think that the supplies are limited, so it may not be as easy as saying, 'We just want to order the Moderna vaccine,' or whatever."
'Better alternatives'
In Thailand, the opposition Move Forward party is now calling on the government to reveal the percentage of people who have only received the Sinovac shots.
"The government already knows that studies and research show inactivated virus vaccines are less effective against virus mutations when compared to mRNA-based vaccines," said Wiroj Lakkhanaadisorn, an opposition lawmaker and a key critic of the government's vaccine policies. "We should know the vaccination rate that excludes all two-dose Sinovac shots because the immunity may not be enough any more. Any regions that are ready can then reopen."
Thailand's health ministry didn't respond to a request for comment.
Chaowat, the teacher, said he felt pressured to take the Sinovac shot because of his job but is hoping to get a Moderna shot in a month or two.
"The government is turning away from Sinovac because they have to push through with their reopening plan and they want to reduce vaccine hesitancy among people who don't want Sinovac," he said. "They're turning to better alternatives."
Beijing refuses to allow Western shots even though development of homegrown ones lags.
Bloomberg Businessweek
Covid vaccination at a mobile site in Beijing on April 9.Photographer: Chen Zhonghao/Xinhua News Agency/eyevine/Redux
Weeks into aCovid-19 outbreak in Shanghaithat brought China’s financial hub to a standstill, the government of President Xi Jinping has demonstrated its willing togo to extremesin 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?”
Share of Population Fully Vaccinated Against Covid-19
As of April 24
Source: Compiled by Bloomberg
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.
An exhibitor shows two packets of an mRNA vaccine co-developed by Walvax Biotechnology at the China International Technology Fair in Shanghai in April 2021.
Photographer: FeatureChina/AP Photo
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
Workers from a public service organization deliver vegetables to residents of a Shanghai neighborhood in lockdown on March 29. Photographer: Hector Retamal/AFP/Getty Images
China’s Covid Zero strategy has been drastic and effective, saving lives and keeping the economy on track. But a new wave of virus cases is highlighting the growing costs of that approach – as well as the perils of any attempt to change it.
Authorities are fighting to curb the spread of the omicron variant among a population that lacks natural immunity and only has access to home-grown vaccines that are less effective than some of the global alternatives. Shanghai – the country’s financial center – is locking down just weeks after the technology hub of Shenzhen was forced to do so.
For the rest of the article refer to the link below ...
(July 16): There is a substantial gap in the amount of antibodies that mRNA and inactivated vaccines can generate against the virus that causes Covid-19, according to a Hong Kong study, in the latest finding on what may have contributed to the varied outcomes following mass vaccination using different types of shots.
Bloomberg
/
Bloomberg
July 16, 2021 13:16 pm +08
The research, published in The Lancet on Thursday, found that antibody levels among Hong Kong health workers who have been fully vaccinated with BioNTech SE's mRNA shot are about 10 times higher than those observed in the recipients of the inactivated vaccine from Sinovac Biotech Ltd.
While disease-fighting antibodies don’t account for the full picture when it comes to measuring the ability to generate immunity and the effectiveness of Covid vaccines, “the difference in concentrations of neutralizing antibodies identified in our study could translate into substantial differences in vaccine effectiveness,” the researchers said.
The finding adds to a growing body of evidence suggesting the superiority of mRNA vaccines in providing potent and comprehensive protection against Sars-CoV-2 and its variants, compared to vaccines developed by more traditional methods such as inactivated shots.
Countries from Israel to the US that have relied mostly on mRNA vaccines from Pfizer Inc and its German partner BioNTech, as well as Moderna Inc, have seen a marked reduction in infections. Those using mostly inactivated shots from China’s Sinovac and Sinopharm haven’t experienced as much of a dent in case numbers, though the use of both kinds has significantly prevented more severe Covid and fatalities.
The lower effectiveness of inactivated vaccines has prompted countries from Thailand to the United Arab Emirates to offer already fully vaccinated people another booster shot as the more infectious delta variant fuels a resurgence in infections.
The Hong Kong study also suggested that future research could look into how booster shots can shore up antibody levels and protection among people vaccinated with inactivated shots.
The lower protection rates of China’s Covid-19 vaccines have raised concerns about shots that are key to inoculation rollouts from Brazil to Indonesia, especially after their efficacy wasquestionedby one of the most senior Chinese health officials.
Bloomberg News
China CDC chief fueled concern by noting their lower efficacy
Experts decode Sinovac’s varying rates, how to improve them
Bloomberg spoke to two experts about the vaccines, zeroing in on the Sinovac Biotech Ltd.shot, which has been the focus of acrisis in confidenceafter it posted efficacy levels of just above 50% in a final stage trial in Brazil -- the minimum required by leading global drug regulators. Other Chinese immunizations have delivered rates between 66% to 79%, still far below the shots developed byPfizer Inc.,Moderna Inc.and even Russia’s Sputnik vaccine that have logged protection rates of more than 90%.
More than 30 countries have rolled out the Sinovac shot, most of them in the developing world, but also Hong Kong. The vaccine is key to China’s own mammoth push to inoculate 560 million people -- 40% of its population -- by the end of June.
The good news is the vaccines work extremely well in combating severe Covid infections, according to Fiona Russell from the Murdoch Children’s Research Institute in Melbourne and Paul Griffin, a professor from the University of Queensland in Brisbane. We asked them key questions about the merits of the Sinovac shot. Their comments have been edited and condensed for brevity.
How effective is the Sinovac vaccine really?
Russell: The Sinovac study was to look at how the vaccine works against the entire range of clinical symptoms, from mild infections to severe ones, including death. The efficacy data of about 50% is for very mild disease, requiring no treatment. For infections requiring some medical intervention, it’s about 84% and for moderate-to-severe Covid cases, it’s 100%.
That’s what you expect from Covid vaccines -- higher efficacy against more severe infections and lower against milder ones. From what I can see, it looks like a very worthwhile vaccine. The problem with the data is it didn’t include many old people or many people with co-morbidities.
Griffin: My impression is the efficacy seems likely to be above the minimum threshold set by the World Health Organization but less efficacious than a number of other leading vaccine candidates. While it may be less effective against symptomatic Covid (mild infections), the efficacy in severe cases is very high, which is an incredibly valuable property of any vaccine, including this one.
Why does it have varying efficacy rates in different studies?
Russell: This has caused a bit of confusion. The trials were done in Brazil, Indonesia and Turkey. Each of the studies have come with different results. In Brazil, you’ve got the P.1 variant circulating and so potentially the vaccine efficacy may be different due to that. I’m not familiar with what was circulating in Turkey or in Indonesia at the time of the study but that could obviously change the results.
Also, it’s very hard to directly compare results from different trials because they have to be interpreted in the context of the study design. The case definitions -- the way a Covid-19 case is identified in a clinical trial -- they used were different, so were the endpoints of the studies.
Griffin: This shows how variables in clinical trials can impact the results. Different strains circulating in a nation are a big variable that can alter the efficacy readout. Virus strains are vitally important in determining vaccine efficacy.
What can be done to improve the vaccine?
Russell: The recommended schedule for two doses of the Sinovac shot in the trial was two weeks, though some people spread it longer than that, even one month apart. Theoretically, tweaking the schedule is definitely an option. Mixing vaccines -- starting with one type and then boosting it with a different one -- is another option but there’s a lot more we need to know about those variations.
Griffin: It’s very likely that the dosing interval is critically important and certainly sounds like it was a variable in Sinovac’s clinical trials as well. We need another clinical trial to ascertain whether adding another booster increases efficacy. In terms of heterologous boosting -- using a mix of different vaccines -- the research is underway. A lot of people are optimistic but until we have the data, it’s hard to know.
Is it possible to reach herd immunity with Sinovac?
Russell: That depends on a number of things -- the circulating variant, the coverage required and the degree to which the vaccine prevents virus transmission. But we don’t have a lot of data yet on transmission.
Griffin: If we have a less effective vaccine, we are going to need to inoculate more people to achieve that. Its potential to reduce virus transmission is likely to be less too but again, without good data its hard to be sure. With very high coverage, even a moderately-effective vaccine is perhaps better than a highly-effective vaccine with poor coverage. So, it depends on the uptake among other factors.
Russell: I would have no hesitation, provided it secures regulatory authority approval. For protecting people from ending up in hospitals, Sinovac’s shot looks terrific as the efficacy data for preventing hospitalization and death is 100%.
Griffin: Yes. While it may mean that we don’t reduce the cases overall or achieve herd immunity, we will still be successful in reducing severe Covid infections and therefore, the burden on the health care system. If the vaccine is approved by the relevant regulators, then I think we need to have faith that it’s safe and effective in that population.
If there are multiple vaccines available, then people could potentially opt for one that has demonstrated superiority in clinical trials. But if that’s not possible, then having this vaccine is better than not being vaccinated at all.
