Pediatric COVID-19 Vaccine Face-Off Looms As Bharat Biotech Heads For Approval
Supply, Acceptance Key
Executive Summary
While Bharat Biotech is close to an accelerated approval of Covaxin in two to 18-year-olds, Zydus Cadila is yet to roll out its COVID-19 vaccine in India. As they head to a face-off in pediatric vaccines, the former faces manufacturing constraints and the latter hesitance over a first of its kind DNA vaccine. Experts speak to Scrip on which one stands a better chance of winning.
Bharat Biotech’s COVID-19 vaccine, Covaxin, was recently recommended by a subject expert committee for accelerated regulatory approval by the Drugs Controller General of India (DCGI), for use in the two- to 18-year-old age group.
Apart from setting off a debate on the wisdom of vaccinating children before a significant proportion of adults is fully immunized, the development is likely to see an interesting battle between two companies over pediatric COVID-19 vaccination.
Covaxin (BBV152) is now just a step away from being the only COVID-19 vaccine approved for use in this young a cohort anywhere in the world. In India, Zydus Cadila’s Zy-CoV-D was the first to be approved for individuals 12 and above and the company intends to apply for trials in the two- to 12-year age group as well.
41% of India's population was below the age of 18 according to the 2001 government census and with a nearly 1.4 billion population in 2021, estimated by Worldometer based on elaboration of United Nations data, that translates to 573 million - not a small number by any imagination.
“Parents are worried and have been enquiring when a vaccine would be made available for kids. I expect a lot of demand and unnecessary pressure on practitioners to immunize children.” - Dr. Vipin Vashishtha, Consultant Pediatrician, Mangla Hospital and Research Centre, IndiaQuestions were initially raised over whether children need to be vaccinated against COVID-19, a disease which has caused an overwhelming number of fatalities in the adult population while resulting in mild to moderate symptoms in children.
However, infections and hospitalizations among children have been growing. In the US, nearly six million children had tested positive for COVID-19 by October, despite about 45% of 12- to 17-year-olds in the U.S. being fully vaccinated, according to a report from the American Academy of Pediatrics.
In Israel, after public schools opened on 1 September, a little over 54% of positive tests were in children aged zero to 19, according to the country's Ministry of Health's COVID-19 dashboard.
As governments across various Indian states move to reopen schools in a phased manner, demand for the vaccination of children is expected to ramp up very quickly. The latest survey on LocalCircles, an online community platform, shows only 7% of adult respondents, the lowest ever, remain hesitant about COVID-19 vaccination, though how many would get their children vaccinated has not been studied.
Speaking to Scrip, Dr Vipin Vashishtha, consultant pediatrician at the Mangla Hospital and Research Centre in North India, questioned the need for vaccinating children at a time when “the focus should be on the adult population,” particularly in countries like India which are facing vaccine shortages.
However, he also acknowledged that from a parents’ perspective the approvals could not come sooner. Against this backdrop, Scrip examines which COVID-19 vaccine could end up the winner in the pediatric segment.
Technology Used
Bharat Biotech has used a tried and tested method of making inactivated vaccines for Covaxin, while Zydus Cadila has pioneered the world’s first plasmid DNA vaccine for human use with Zy-CoV-D.
The vaccine represents a commendable technological breakthrough for Zydus Cadila and its needle-free application will be a less painful experience compared to standard injections. But the DNA technology will also very likely lead to questions over its long-term safety in the minds of parents or guardians.
“Zy-CoV-D is a user-friendly vaccine but I’m a bit skeptical over its safety. Generally, a Phase III trial enrolls volunteers in the thousands but in a real-life setting it will be administered to several millions and that is when the rare adverse events come to light. It happened with Moderna, Inc. and Pfizer Inc.’s mRNA vaccines showing myocarditis and other such effects and the same could happen with Zydus Cadila’s vaccine as well,” pediatrician Vashishtha told Scrip.
Covaxin has also resulted in side-effects and physicians are expected to conduct a risk-benefit analysis when a child comes to them for vaccination. Even if rare or very rare, parents might prefer to err on the side of safety as far as children are concerned.
Pricing Of Vaccines
While Covaxin has been used in India’s immunization program since January for individuals 18 and above, Zy-CoV-D is yet to be launched post an emergency approval in August.
Zydus Cadila claims to have vaccines in stock but discussions with the union government seem to be stuck over pricing. It has reportedly quoted less than INR300 ($4) for a single dose of its vaccine, whereas the government has bought Covaxin at INR225 a dose and AstraZeneca PLC partner Serum Institute of India Pvt. Ltd.’s Covishield at INR215/dose.
The currently approved three-dose regime of Zy-CoV-D (a two-dose one is under regulatory consideration), compared to the two-dose one for Covaxin and an electroporation device which needs to be imported and supplied along with the vaccine, complicate the equation for Zydus. The injector can reportedly be used for around 20,000 doses.
The union government has so far been supplying vaccines free of cost for the nationwide COVID-19 immunization program, and the Zydus Cadila option will present a higher burden on the exchequer.
However, Covaxin has been priced at INR1,200 a dose for private hospitals administering the vaccine and this segment presents a fair opportunity for Zy-CoV-D as the government has permitted individuals to get immunized outside of its network as well. (Also see "Focus On J&J, Pfizer COVID-19 Vaccine Pricing As India Permits Private Sales" - Scrip, 20 Apr, 2021.)
Manufacturing Constraints
Bharat Biotech has been constrained in its capacity to make Covaxin as it needs biosafety level-3 (BSL-3) laboratories for the manufacturing process given that the vaccine comprises whole virion, inactivated viruses.
Hardly any other vaccine companies in India have BSL-3 labs and of the three tie-ups entered so far, with Indian Immunologicals Ltd, Haffkine Biopharmaceutical Corporation Ltd and Bharat Immunologicals and Biologicals Corporation Limited, only Indian Immunologicals has begun supplying drug substance to Bharat Biotech. The other two will take more time, possibly well into 2022, to build and ramp up capabilities.
Bharat Biotech has been reluctant to engage contract manufacturers outside India thus far, perhaps on account of non-availability or potential implications on domestic pricing. Its inability to increase supplies has meant only roughly 12% of doses given in India have been Covaxin shots. (Also see "Can Delta Variant Effectiveness Fill Brazil-Sized Hole In Bharat Biotech’s Prospects?" - Scrip, 5 Aug, 2021.)
Meanwhile, Zydus Cadila needs BSL-1 labs and minimal safety requirements mean a higher capacity to boost production. The company has roped in Shilpa Medicare subsidiary Shilpa Biologicals Pvt. Ltd. to make the drug substance and intends tying up with more suppliers for the DNA vaccine.
Which Vaccine Scores Higher?
The verdict from experts favors Bharat Biotech, though it will face a challenge in raising supplies sufficient for both the adult and pediatric populations. (Also see "Global Herd Immunity Against COVID-19 Unlikely, Says Ebola Vaccine Developer" - Scrip, 20 Jul, 2021.)
Vaccines expert and former CEO of Hilleman Laboratories Pvt. Ltd., Davinder Gill, said “based purely on superficial knowledge that most parents might possess, my guess is Bharat Biotech’s vaccine would be preferred since it doesn’t contain DNA and might therefore be perceived as safe for children.”
There’s no denying that both children and adults will need to be immunized as the disease becomes endemic and herd immunity is no longer a viable option.
However, how soon children in India will begin to get shots in their arms remains to be seen, given that by end-September, only 25% of the country’s adult population had been fully immunized, while 69% had received at least one dose.
In addition, a need for boosters, especially for the immune-compromised population and front-line healthcare workers, could further suck up available supplies.