Covid Decline May Slow Vaccine Efficacy Testing

New Delhi, 11 Jan 2021:

A sharp drop in the number of covid-19 cases may handicap vaccine developers that are likely to start testing the effectiveness of their shots and potentially delay their approvals in India, where the first phase of the world’s largest immunization programme is set to start next week.

Testing the effectiveness of vaccines, which is established in phase 3 of clinical trials, requires volunteers who have been infected by the coronavirus.

“Unless they do the trial in, say, Kerala, where daily cases are still high, it will take a lot of time for some of the participants across the placebo and vaccine arm (of the trial) to be infected. This means that it will take longer to get efficacy readings for the next batch of vaccines," said Vineeta Bal, professor of biology at Pune’s Indian Institute of Science Education and Research.

While the decline in daily new cases is definitely a positive development, it becomes harder for vaccine developers to conduct large-scale studies. With the daily coronavirus infections dropping to less than 20,000 in the country from nearly 100,000 in September, studying the effectiveness of the vaccine is likely to be dragged out.

Among the Indian covid-19 vaccine developers that are still to conduct phase 3 efficacy trials are Zydus Cadila, Biological E and Gennova Biopharmaceuticals.

While Zydus Cadila’s vaccine ZyCov-D is set to start phase 3 trials, Biological E is conducting phase 1 trials and Gennova Biopharmaceuticals will soon start trials.

Zydus Cadila’s vaccine may miss its April launch target as the three-dose experimental vaccine has to be given to volunteers over nearly two months.

Trial participants will then have to be monitored to check whether the shots are effective.

“If Zydus lines up volunteers for the trial even from tomorrow, and they do large-scale recruitments, it is very unlikely that they will have early reports on protective efficacy even three months from now because the participants have to be observed for 30-35 days after the booster shots are given to see how many have got covid-19," Bal said.

The Ahmedabad-based company got Drugs Controller General of India’s (DCGI’s) approval for a 30,000-participant efficacy trial last week.

“We will wait to see results from phase 3 data to understand when the protection begins after immunization," Renu Swarup, secretary of the department of biotechnology, said in a statement in response to a query sent on Saturday. The department is partnering with Zydus Cadila for the development of the vaccine.

Zydus Cadila did not respond toqueries emailed on Thursday.

For Gennova, the issue would be proving the safety of its messenger RNA vaccine, the latest technology in vaccine manufacturing.

Gennova chief executive Sanjay Singh said that the company could expedite its phase 3 trial if the DCGI allows the company to use ‘correlates of protection’ data provided by Pfizer and Moderna as a benchmark for its vaccine trial.

Pfizer and Moderna recently got authorization for their mRNA vaccines after clearances in the US and some other countries.

However, experts have pointed to differences in the technologies used by Gennova and the US vaccine makers.

Gennova’s vaccine uses self-replicating RNA, while the US firms use non-replicating RNA, which may lead to differences in the safety of the vaccines.

While the Biological E vaccine is considered to be safe by experts because it uses a traditional platform, a late start could further delay its development.

Dr Reddy’s Laboratories is also conducting a phase 2 and 3 bridging study for Russia’s Sputnik V vaccine, while Serum Institute of India plans to soon start conducting a similar trial for Novavax’s protein subunit shots.

Unlike an efficacy trial, a bridging study just looks at the safety and immune response data to show that the shots work in the Indian population or, in case of contract manufacturing, that they are similar to the original version.

Last week, DCGI gave emergency licensure to Serum Institute of India’s Covishield and Bharat Biotech International’s Covaxin. While Covishield was given an authorization after the firm conducted a bridging study, the authorization to Bharat Biotech’s Covaxin was given in ‘clinical trial mode’ due to the lack of efficacy data.

The government on Saturday said it plans to start vaccination from 16 January. Livemint