Can China Convince World With Its Fast, Cheap COVID Vaccines?
Candidates Gain Traction Outside West
Executive Summary
As China gears up to the possible launch of its first vaccines against the coronavirus, supported by clearer regulations, many see the candidates as promising and cost-effective, although they may need more convincing data to be widely adopted. Relatively low projected per dose costs are generating interest in trials in multiple countries.
Amid a global race to launch the first vaccine against the coronavirus and after Russia became the first nation to approve its candidate - albeit based on only small trials and limited data - many are now turning their attention to China, a front-runner with multiple vaccines now in final-stage development.
One Chinese health official recently disclosed that as early as 22 July, the country had issued emergency use authorizations (EUAs) to domestic COVID-19 vaccines still in late clinical trials. The director of the Technology Development Center at the China National Health Commission (NHC), Zhongwei Zheng, noted that China had initiated an EUA, but did not disclose for which of the three leading candidates.
The move is the latest step towards enabling the vaccination of large numbers of citizens with a still experimental candidate that has yet to be officially approved. The disclosure also signaled the Chinese government’s eagerness to have the first vaccines for the global pandemic.
However, any approval under the EUA mechanism can only be formally issued by the new product review agency, the National Medical Product Administration (NMPA), not the NHC, which oversees healthcare service providers.
“This is not a true EUA per se,” noted Gang Wang, a former associate director of the US Food and Drug Administration's China Office. “According to the [China] Vaccines Administration Regulation, only NMPA has the authority to issue one,” he explained.
Already In Use
Issued in 2019 in the wake of several quality and distribution scandals, the vaccines regulation - the first of its kind in China - aimed to improve overall oversight of the sector. Outlined in Item 20 is an emergency approval mechanism, which explicitly states that amid a major public health crisis or other emergencies posing threats to public health, the nation’s drug regulators can approve a vaccine with conditions and issue an EUA for use in certain areas and over a preset time frame.
In July, China’s military took the first step to authorizing the use in its personnel of CanSino Biologics Inc.’s adenovirus-based coronavirus vaccine Ad5-nCoV.
Now the new EUAs, despite not being formally issued by the NMPA, could include Ad5-nCoV and two other leading vaccines, one from state-owned Sinopharm Group Co. Ltd. and the other from Sinovac Biotech Ltd.. This could enable their use in a larger population outside the military or state workers.
Already, many state-owned employees required to travel abroad for work have been vaccinated with Sinopharm’s inactivated virus-based vaccine. One internal document made public shows that, so far, as many as 300 people are being vaccinated every day, putting the total at potentially several thousand.
Price Advantage?
According to the internal document, seen by the Pink Sheet, the cost of producing the vaccines in China also appears to be comparatively lower than those moving forward in the US and Europe.
The production cost is estimated to be CNY20 ($2.80) per dose on average, with the inactivated virus-based vaccines having the lowest cost, followed by the adenovirus-based candidate and then recombinant protein and mRNA-based products.
In comparison, the vaccines being developed by Pfizer Inc. and BioNTech SE were procured by the US government at a cost of $19.50 per dose and $39 for the two-dose regimen. (Also see "Pfizer’s Go-It-Alone Approach Nets $1.95bn COVID Vaccine Order From US Government" - Pink Sheet, 22 Jul, 2020.)
The US government procurement price for other vaccines varies (the per dose calculation also depending on whether R&D funding is taken into account), with Johnson & Johnson's single-dose, adenovirus-based candidate for instance being among the lowest at around $14/dose, including R&D grants. (Also see "Coronavirus Notebook: Middle Ground Pricing As Moderna Reaches 100m Dose US Agreement" - Pink Sheet, 12 Aug, 2020.)
So far, no countries in the west have indicated any intention to use made in China vaccines. In the US, the public face of the fight against the pandemic, Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, told US congressmen during testimony on 1 August that, "I do hope that the Chinese and the Russians are actually testing the vaccine before they are administering the vaccine to anyone."
As Washington under the pre-election Trump Administration moves to buy American for essential medicines, and as the president repeatedly blames China for the pandemic, the likelihood of the country procuring Chinese vaccines looks close to zero.
Gaining Traction Elsewhere
But the apparent cost advantage may be one factor giving the Chinese vaccines increasing traction in countries in Southeast Asia, Latin America and Northern Africa.
The United Arab Emirates, Saudi Arabia, Brazil, Chile and Mexico have all expressed interest in developing the vaccines in local markets, while some large-scale Phase III studies area already being conducted in the UAE, Brazil and the list is getting longer.
Morocco, Peru and Argentina (through local partner ELEA) have become the latest nations to recently authorize Phase III trials for Sinopharm’s vaccine, developed by its subsidiary China National Biotec Group. That takes the total countries involved in the studies to five, after the UAE and Bahrain.
Meanwhile, Sinovac on 25 August signed a collaboration with Bio Farma Indonesia to supply a minimum of 40 million doses of CoronaVac by March 2021. Currently, a local Phase III study of CoronaVac is being carried out by Bio Farma. While it encountered a slow start for its Phase III program, CanSino has now teamed up with authorities in Saudi Arabia for Ad5-nCoV.
With China’s supportive regulatory agency ready to step in, the speed of enrollment and results from these studies will largely decide how soon China will have its first approved COVID-19 vaccine.
The internal document shows that, although it usually takes one year for a Phase III study to complete, developers can have preliminary data in as short as three months towards an emergency approval in China, as outlined in the vaccines regulation.
Approval Threshold?
On 14 August, the Center for Disease Evaluation at China's NMPA also issued technical guidelines for coronavirus vaccine development in China.
The review body requires final-stage clinical trials to assess the effectiveness of protection, but developers may consider changing the immunogenicity procedure either during Phase III or optimizing this after getting a production registration.
“The purpose of Phase III clinical trials is to evaluate the effectiveness and safety of candidate vaccines, including the evaluation of vaccine protection effectiveness, the exploration of the correlation between immunogenicity indicators and protection, and the expansion of target population safety evaluation, which can be conducted throughout the target population or in a related subpopulation group,” the technical guidelines explain.
However, unlike the US FDA, which has required a minimum 50% effectiveness threshold, the Chinese regulator did not outline such a clear hurdle for the vaccines to pass.
Given all these developments, China may need to wait for more data to support the safety and efficacy of its vaccines before clearing them for use in a large public population, some observers say.
Referring to those in China who are already being vaccinated before any formal product approvals, ex-FDA China office director Wang suggested there may be associated study subject protection issues.
"They are either being misled to believe the safety and efficacy of the investigational vaccine or have no other choice but to be vaccinated before they could take on a specified assignment, such as working as aid workers or laborers."