Preparing for the third wave

A recent International Monetary Fund (IMF) report’s prediction that vaccine coverage in India could remain under 35 per cent of our population by this year-end, inspite of the government’s claim that the full population would be covered, is worrying at several levels.

From a public health perspective, the under-vaccinated will still be vulnerable to the infection and therefore lead to many subsequent waves. From an economic perspective, while the pandemic is lowering business sentiment, it is also an opportunity for sectors like pharmaceuticals, medical devices and hospitals to scale up. Even if we need global help to meet today’s needs, we have to shore up infrastructure for subsequent waves of this and future pandemics.

Indeed, even as overseas companies are holding out for pre-orders, advance payments and indemnity clauses, the government has finally given in and waived local clinical trials for “well-established companies”. No company can ignore the size of the Indian population and the market it represents. Especially as it looks like annual SARS-CoV2 booster shots will be required for at least a couple of years.

Which is why Bharat Biotech has applied for approvals in more than 60 countries. Other vaccine manufacturers from India too will do the same, not just to shore up exports but to ensure that vaccinated citizens will be allowed to travel to as many countries as possible, once they have key approvals in place. The era of vaccine passports is already a reality today.

As the vaccine and medical device supply chains are being re-jigged, so must the API supply chain, especially for medicines required for COVID-associated conditions like mucormycosis, for example. Medicines to treat fungal infections were usually manufactured in small volumes as the number of cases were much lower. Now, Mumbai-based VAV Life Sciences, which is reportedly the only Indian company that makes the highly purified synthetic lipids needed to produce Amphotericin B formulations, the medication used for treating black fungus infections, finds itself scrambling to scale up from a monthly capacity of 21 kgs to 65 kgs by August, and a further increase to 130 kg per month by December, as per Arun Kedia, MD, VAV Life Sciences.

The clinical trials sector in India is also seeing a revival. Biotech and biopharma clinical trial sites in the Asia Pacific have increased by over 40 per cent each year on average, compared to just 11 per cent across the rest of the world, as per some estimates. Thus it is no wonder that major CROs like IQVIA Biotech recently announced their launch in India, along with across the Asia Pacific and Japan (JAPAC) region.

But as we rush repurposed medicines through clinical trials in the race to get emergency use authorisations for COVID-19 use, properly conducted clinical trials will be very important to determine the true value of such molecules.

Dr Arun Bhatt, a clinical research and drug development consultant points out the COVID-19 trials and tribulations in a recent article (https://www.expresspharma.in/covid-19-trials-and-tribulations-for-treatments/) explaining how a majority of clinical trials of repurposed drugs in India suffer from a high risk of bias. Most have been conducted in a small population of mild and moderate COVID-19 patients, using viral clearance, or clinical scale as efficacy endpoints. He points out that viral load reduction, as an endpoint is difficult to assess because of sensitivity and specificity limits of RT-PCR, and discordance between detection of virus from nasal and oropharyngeal swabs. Also, there is no established predictive relationship between the magnitude and timing of viral reductions and the extent of clinical benefit for a patient.

Dr Bhatt mentions the most recent example of such a trial, for 2-Deoxy-D-Glucose, which recently received the DCGI/CDSCO nod. He flags one major concern as the safety in COVID-19 patients who can suffer from myocarditis and develop diabetes mellitus.

The WHO’s recently released World Health Statistics report 2021 and global COVID-19 excess mortality estimates warn that the COVID-19 deaths could be at least two to three times higher, based on preliminary excess mortality estimates for 2020. Globally, and in India, deaths in 2021 have already surpassed cases and deaths reported in the whole of 2020. Thus, while we cannot afford to get complacent once more, neither can we rush through clinical trials or approvals.

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