Candidate: CoronaVac (formerly PiCoVacc)
Category: VAX
Type: Formaldehyde inactivated vaccine with alum adjuvant
2021 Status: Booster Dose Effective vs. Delta—In a preprint posted September 5 on medRvix, researchers reported that a third dose of CoronaVac increased the potency, scale, and duration of anamnestic responses against SARS-CoV-2. A full course immunization with Sinovac’s inactivated vaccines could effectively protect against severe illness caused by the Delta variant, according to research results of the real-world study on patients infected with the Delta variant in the recent outbreak in East China’s Jiangsu Province.
“Our results demonstrate that a third dose booster of inactivated vaccine can elicit an expeditious, robust and long-lasting recall humoral response which continues to evolve with ongoing accumulation of somatic mutations, emergence of new clones and increasing affinities of antibodies to antigens, conferring enhanced neutralizing potency and breadth,” the researchers wrote.
Deaths, Hospitalizations Reduced–CoronaVac showed a 95% reduction in deaths, and an 86% reduction in hospitalizations, between February and April following inoculation of 95% of all adults in Serrana, Brazil—about 27,000 (60%) of the town’s 45,000 people, according to study results released by researchers at the Butantan Institute, a Brazilian state-funded research institution that serves as Sinovac’s research partner in Brazil.
The adult population also showed a decrease of 80% in symptomatic cases over the duration of the “Project S” study after receiving both doses of the vaccine, Sinovac said June 1 in a statement to China’s state-owned Global Times news outlet, published under the auspices of the Chinese Communist Party’s People’s Daily newspaper. CoronaVac accounts for almost 80%of all COVID-19 vaccine doses administered in Brazil, according to China’s state-owned Xinhua news agency.
In a preprint posted May 22 on medRxiv, a team of Brazilian researchers reported that 129 of 133 healthcare workers (97%) inoculated with CoronaVac at the Complexo Hospital de Clinicas, in Curitiba, Brazil, developed antibodies against the S1 protein 40 days after they received their second dose of the vaccine. Also, 69 of the 133 staffers (51.87%) developed antibodies against the N protein—a result that the researchers concluded “could be valuable with the emergence of SARS-CoV-2 variants, considering the lower mutation levels in this protein, compared to the high mutation levels in the S1 protein.”
“Seroconversion of N-protein antibodies may be an alternative for the vaccine industry to produce efficient vaccines for circulating strains, including those that may arise in the future,” the Brazilian researchers added.
Dimas Tadeu Covas, Coordinator for Sinovac’s Brazilian clinical partner Instituto Butantan, told reporters February 18 that CoronaVac showed “good results” against the U.K. (B.1.1.7) and South African (B.1.351) variants of SARS-CoV-2, without elaborating. Speaking in Serrana, Brazil, Covas also said Butantan is assessing CoronaVac against the Brazilian variant (P.1).
Conditional marketing authorization granted February 5, 2021—China’s National Medical Products Administration said February 6 that it gave conditional marketing authorization to Sinovac for CoronaVac a day earlier. The application was submitted by a Sinovac entity, Beijing Kexing Zhongwei Biotechnology Co., Ltd., and came eight months after NMPA authorized CoronaVac for emergency use. (Sinovac announced the conditional authorization on February 8).
CoronaVac is the second vaccine developed by a Chinese company to obtain an approval from the agency. The first was the vaccine developed by Sinopharm (China National Pharmaceutical Group Co.). However, both approved vaccines are only authorized for patients ages 59 and younger.
Also on February 5, Sinovac announced data from a 12,396-participant, Phase III trial in Brazil and Turkey showing CoronaVac to be 100% effective in preventing death or hospitalization in patients with COVID-19, 83.7% effective in avoiding cases that required any medical treatment, but just 50.65% effective at preventing infection with the virus. The trial assessed the effectiveness of the two-shot vaccine trials evaluated the efficacy of the two-shot vaccine candidate 14 days after inoculation of participants, which including healthcare workers who treat COVID-19 patients.
Among Turkish participants, which included both healthcare workers and the general population, CoronaVac showed a 91.25% efficacy rate in preventing COVID-19 based on an analysis of 29 cases. More than 25,000 people outside China have taken part in CoronaVac clinical trials, according to Sinovac.
Turkey’s Health Minister Fahrettin Koca said January 24 that 6.5 million doses of CoronaVac were to arrive in Turkey the following day, with another 3 million doses having arrived earlier.
Brazil’s health regulatory agency Anvisa on January 17 authorized emergency use of CoronaVac as well as the AstraZeneca/University of Oxford co-developed AZD1222 as vaccines to protect against COVID-19.
2020 Status: Sinovac on December 7 reported $6.622 million in sales and gross profit from CoronaVac during the third quarter of 2020, accounting for 5.7% of total company sales during Q3 and 3.6% of total sales for the first nine months of 2020, according to quarterly results released by the company.
A day earlier, Sinovac said the Chinese pharmaceutical conglomerate Sino Biopharmaceutical invested approximately $500 million in a Sinovac subsidiary, Sinovac Life Sciences, in return for a 15% stake in Sinovac. The investment is intended to fund further development, capacity expansion and manufacturing of CoronaVac, as well as conduct other development and operational activities, Sinovac said.
Weidong Yin, Sinovac’s Chairman, President and CEO, said in a statement that the investment from Sino Biopharmaceutical “further enables us to improve our vaccine sales capabilities, expand in Asia markets, develop and access new technologies, and most importantly, accelerate our efforts to help combat the global pandemic.”
As of December 6, Sinovac said, Phase III clinical trials for CoronaVac had been approved in Brazil, Indonesia, Turkey, and Chile. In China, Phase I/II trials showed the vaccine candidate to induce neutralizing antibodies in over 90% of volunteers who received two doses of vaccination. Results from that trial on healthy adults aged 18-59 years old were published November 17 in Lancet Infectious Diseases.
Sinovac also said it expects to be able to manufacture 300 million doses annually and aims to complete the construction of a second production facility by the end of 2020 to increase its annual production capacity of CoronaVac to 600 million doses. The company added that it may seek to further expand its production capacity depending on market conditions and the availability of financing.
The Jiaxing, China, Center for Disease Control and Prevention posted a statement on WeChat on October 16 announcing that it is offering to vaccinate essential workers and other high-risk groups with Sinovac’s CoronaVac, Reuters reported. The company had not responded to a request for comment on the report, which added that two doses of the vaccine candidate, called CoronaVac, will cost 200 yuan ($29.75) per dose.
On October 2, Japan’s Ministry of Health, Labour, and Welfare approved free distribution of a single dose of CoronaVac to all Japanese citizens. Whether the policy will cover foreign residents in Japan has yet to be officially determined, a ministry official told The Japan Times.
The government of São Paulo, Brazil agreed September 30 to purchase 46 million doses of CoronaVac from Sinovac for about $90 million. The contract formalizes an earlier agreement under which Sinovac agreed to deliver 60 million doses to authorities in São Paulo by the end of February. The first doses are expected to reach patients starting in December 2020. Sao Paulo Governor João Doria told reporters that his state and Sinovac have an oral agreement covering the delivery of the other 14 million doses.
CoronaVac is in a Phase III trial, the first results of which are set to be released in December, Sinovac’s Latin America head, Xing Han, said in September.
Sinovac said September 22 that it began Phase III trials for CoronaVac in Turkey. The trial is designed to test the vaccine’s efficacy and safety, and aims to serve as a pivotal study to support regulatory applications for licensure.
In the first stage of the randomized, double-blinded, and placebo-controlled Phase III trial, 1,300 healthcare workers ages 18-59 years old will randomly receive two doses of vaccine or placebo at a two-week interval. In the second stage, approximately 12,000 members of the general population between ages 18-59 years old will be enrolled to receive two doses of vaccine or placebo at a two-week interval.
In August, Sinovac signed two agreements of undisclosed value with PT Bio Farma for the supply, local production, and technology licensing of CoronaVac. Sinovac committed to supplying Bio Farma bulk vaccine, enabling the company to produce at least 40 million doses of CoronaVac in Indonesia before March 2021, to be priced at about 200,000 rupiah ($13.60) per dose. After March 2021, Sinovac said, it will continue to supply the required quantity of the bulk vaccine until the end of 2021.
Bio Farma is conducting a Phase III clinical trial for CoronaVac in Bandung, Indonesia. The study will ensure Indonesia has early access to CoronaVac without compromising safety, Sinovac said.
Sinovac said the agreement reflected its willingness and commitment to developing and supplying vaccines against COVID-19 for global use at “affordable” prices.
The Indonesia trial is one of two Phase III studies launched by Sinovac. The other is a 900-volunteer trial that Sinovac is conducting with Brazil’s Instituto Butantan, which distributes 65% of all vaccines distributed in the country. The volunteers are doctors and other health workers working across six of Brazil’s states.
The Brazilian trial will start at the Clinical Hospital of Sao Paulo, the state’s governor Joao Doria told reporters, adding that initial results were expected within 90 days. Should the vaccine prove safe and effective, the institute will have the right to produce 120 million doses of CoronaVac
In June, Sinovac trumpeted positive preliminary results of its Phase I/II clinical trial for CoronaVac, showing favorable immunogenicity and safety profiles. The Phase II portion of the trial demonstrated that the vaccine induced neutralizing antibodies 14 days after vaccination. The neutralizing antibody seroconversion rate is above 90%, from which Sinovac concluded that CoronaVac can induce positive immune response.
The Phase I/II clinical trials were randomized, double-blind and placebo-controlled studies that recruited a total 743 healthy volunteers aged 18-59 years old. Of those, 143 volunteers were in Phase I, and the other 600 were in phase II. There have been no severe adverse event reported in either the Phase I or Phase II trials, Sinovac stated.
Sinovac said it expects to submit a Phase II clinical study report and a Phase III clinical study protocol to China’s National Medical Products Administration (NMPA) “in the near future,” as well as begin Phase III clinical trials outside of China. Sinovac is collaborating with Instituto Butantan in Brazil to prepare and conduct a Phase III trial, the company said June 11. The Company added that it expects to share full data from its clinical trials through academic publications.
On May 29, Sinovac disclosed it is in preliminary talks with overseas regulators to hold Phase III trials of CoronaVac: “We are speaking to several European countries and I think did discuss with the UK as well,” Helen Yang, senior director of investor relations, told UK-based Sky News.
A week earlier on May 22, Sinovac said it commenced a Phase II trial designed to assess the immunogenicity and safety of CoronaVac in a larger population in order to define dosage, regimen and immunization schedule. The trial began following preliminary observation of the safety profile of CoronaVac in the Phase I study, which evaluated the safety, tolerance, and preliminary immunogenicity of the vaccine, Sinovac said.
Sinovac said it is also constructing a commercial vaccine production plant that is expected to manufacture up to 100 million doses of CoronaVac annually.
That same day, Sinovac said its wholly-owned subsidiary Sinovac Research and Development received a total $15 million investment from Advantech Capital and Vivo Capital that is intended to further the development of CoronaVac. Each investor lent the company $7.5 million in the form of a convertible loan that bears interest, or, at the investor’s election, converts into a 7.5% equity interest in Sinovac R&D.
Sinovac CEO Yin Weidong told Bloomberg News May 8 that his company was in talks with regulators outside China and the World Health Organization, to launch Phase III clinical trials in areas of the world where COVID-19 is spreading rapidly. While he would not say where Sinovac is planning the trials, the company has submitted an application to conduct clinical studies in Canada, and Yin at another country when he said: “The U.S. has the most developed biotech industry, the most sophisticated regulatory framework, and its epidemic is now the worst.”
On May 6 in a study published in Science, researchers from Sinovac and collaborating institutions reported that the Sinovac vaccine candidate induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and rhesus macaques (Macaca mulatta). The antibodies potently neutralized 10 representative SARS-CoV-2 strains, which according to the researchers indicated a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide.
“Collectively these results suggest a path forward for clinical development of SARS-CoV-2 vaccines for use in humans,” the researchers wrote. “Phases I, II and III clinical trials with PiCoVacc, as well as other SARS-CoV-2 vaccine candidates, are expected to begin later this year.”
In April, Sinovac said it launched a Phase I/II clinical trial (NCT04352608), a randomized, double-blinded, placebo controlled study assessing its vaccine candidate in healthy adults aged 18–59 Years. Sinovac said it completed enrollment of the first group of volunteers and the first dose of vaccination for these volunteers. Two-thirds of the volunteers will be vaccinated with the investigational vaccine while the other third will be given placebo, Sinovac said.
The trial is being conducted in Jiangsu Province following approval by China’s National Medical Products Administration (NMPA). A total of 744 subjects will be enrolled, with 144 to be studied in Phase I, and 600 at Phase Ⅱ.
The vaccine type is similar to a Phase I vaccine candidate developed by Sinovac against SARS in the early 2000s, VP Meng Weining told Science.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA
