Type: Recombinant Novel Coronavirus Disease Vaccine incorporating a non-replicating Adenovirus Type 5 Vector (Ad5-nCoV)
Status: CanSino Biologics CEO Yin Weidong said September 24 that the company planned to begin distributing Ad5-nCoV to patients worldwide early in 2021—including in the U.S., where he said the company would apply to the FDA for approval if its Phase III trial generates positive results. Yin said he has taken the vaccine, which has been administered to more than 24,000 people in clinical trials held in Brazil, Turkey, and Indonesia, with additional trials set for Bangladesh and possibly Chile.
Pierre Morgon, Senior Vice President for International Business at CanSino, told The Wall Street Journal in an August 28 report that the company is in talks with several countries to get emergency approval for Ad5-nCoV before the completion of Phase III trials. Pakistan is one of the countries, said Morgon, who would not disclose others but did say they include nations in Latin America and some developed nations. The WSJ cited an unnamed “senior Pakistani official” as confirming discussions with the country about emergency use of the vaccine. While COVID-19 cases and deaths had declined sharply over the last few months, Pakistani officials fear they could surge back up this winter.
Officials in Pakistan and Saudi Arabia told the WSJ CanSino was about to enter Phase III trials, a week after Russia’s clinical trials registry disclosed—and Chinese state-owned TV channel CGTN reported—the August 14 launch of a Phase III study by CanSino partner Petrovax, set to enroll 625 participants across eight medical institutes.
China’s National Intellectual Property Administration awarded China’s first patent for a COVID-19 vaccine to a team of researchers from CanSino and the Academy of Military Sciences, according to an August 17 report in People’s Daily, an official newspaper of the Central Committee of the Communist Party of China. The team was led by virologist and epidemiologist Major Gen. Chen Wei, a researcher at the Academy’s Institute of Military Medicine and an academician of the Chinese Academy of Engineering.
Paraphrasing the patent abstract, People’s Daily reported that the vaccine “shows good immunogenicity in both mouse and guinea pig models and can induce strong cellular and humoral immune response in a short period of time. It can be produced quickly on a large scale to cope with a COVID-19 outbreak.”
Researchers from CanSino and partners published results in The Lancet on July 20 from a Phase II study (NCT04341389), conducted with China’s Beijing Institute of Biotechnology, Academy of Military Medical Sciences. The results showed Ad5-nCoV to be safe, with its effectiveness varying depending on the measure.
Both doses of the vaccine resulted in significant neutralizing antibody responses to live SARS-CoV-2, the investigators reported. Receptor binding domain (RBD)-specific ELISA antibody responses induced by the vaccine were detected from day 14 onward, with geometric mean titres (GMTs) of 94.5 and 85.1 in the 1 × 1011 and 5 × 1010 viral particles per mL dose groups, respectively. Seroconversion of binding antibodies were seen in 96% and 97% of participants. However, the vaccine induced seroconversion of neutralising antibodies in just 59% and 47% of participants in the 1 × 1011 and 5 × 1010 dose groups, respectively, and positive specific T-cell responses measured by IFNγ-ELISpot were found in 90% and 88% of participants.
“The antibody and T-cell responses were both very low,” Brad Loncar, CEO of Loncar Investments and an investor in CanSino, told Bloomberg News. “I thought the data was unimpressive.”
In discussing the results, CanSino acknowledged: “Pre-existing immunity to the Ad5 vector and increasing age could partially hamper the specific immune responses to vaccination, particularly for the humoral immune responses.” 95% of participants in the 1 × 1011 viral particles dose group and 91% of the recipients in the 5 × 1010 viral particles dose group showed either cellular or humoral immune responses at day 28.
Of 603 participants who were recruited and screened for eligibility between April 11 and 16, 508 eligible adults aged 18-83 years from a single site in Wuhan, China, agreed to participate in the trial, launched in April. The 508 were randomly assigned to receive either of two concentrations of the vaccine (253 participants received 1 × 1011 viral particles per mL; 129 received 5 × 1010 viral particles per mL) or placebo (126). The trial’s primary endpoints for immunogenicity were the GMTs of specific ELISA antibody responses to the RBD and neutralizing antibody responses at day 28.
CanSino co-founder Qiu Dongxu said July 11 at the China Anti-viral Drug Innovation Summit that his company had contacted officials in Russia, Brazil, Chile, and Saudi Arabia to launch a Phase III trial of Ad5-nCoV. He said CanSino planned to recruit 40,000 participants for the trial, which is set to start “very soon,” state-controlled news agency CGTN and Reuters reported.
Qiu also told the conference that CanSino is now constructing a factory in China that will enable the company to produce 100 million to 200 million doses of COVID-19 vaccines annually by early 2021.
On June 29, CanSino disclosed in a regulatory filing that Ad5-nCoV received “Military Specially-needed Drug Approval valid for one year from the Health Bureau of the Logistics Support Department of the Central Military Commission, the parallel national defense organization of the Communist Party of China and the People’s Republic of China. The approval is limited to military use only, and cannot be expanded to other populations without approval from the Logistics Support Department.
In May, a team of Chinese researchers reported positive safety, tolerability, and immunogenicity data from a Phase I trial for Ad5-nCoV (NCT04313127; ChiCTR2000030906). In a study published in The Lancet, the researchers reported that ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination, while specific T-cell response peaked at day 14 post-vaccination: “Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.”
Last month, CanSino received approval from Chinese authorities to begin human trials of the vaccine, co-developed with the Academy.
CanSino and the Academy are using Sartorius’ BIOSTAT® STR single-use bioreactor system for upstream preparation of the recombinant vaccine, Sartorius said March 25.
The vaccine candidate is the first novel coronavirus vaccine for COVID-19 to advance into clinical trials in China. The company has cited results from animal studies showing that the vaccine candidate can induce strong immune response in animal models.
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: