Why drug repurposing needs first good science, then hope

As India’s COVID-19 positive case count approaches the five lakh count, we are set to become the third most affected country by the SARS-CoV-2 virus. But five odd months after India’s first COVID-19 positive case was registered on January 30, we now have at least a few investigational medicines approved to treat patients.

In fact, the adversity has proved to be an opportunity to galvanise drug repurposing and development in India. Research institutes like CSIR, like peers across the world, have identified candidates and then shared the technology with industry partners to scale up production. The government has given emergency use authorisation to these medicines for use in patients, under strict conditions.

With umifenovir, favipiravir and remdesivir now approved for treatment under these emergency use authorisation conditions, India’s COVID-19 patients have a medication for each stage of the infection. While Glenmark started the FAITH trial with a combination of umifenovir and favipiravir for ‘mild and moderate’ COVID-19 cases, remdesivir is for patients with more severe symptoms of the infection.

Besides the allopathic armamentarium, we also have traditional remedies aimed to improve immunity. And Baba Ramdev is courting controversy once again, by pegging Patanjali’s CORONIL as a cure for COVID-19. This has revived the tug of war between these two camps.

A day after Patanjali claimed that they had conducted clinical trials to prove that it cured COVID-19, came the news that the trials did not include patients with co-morbidities, the cohort that is particularly susceptible to the infection.

As per further reports, Patanjali’s application for a license for Coronil did not mention COVID-19, merely referring to it as an immunity booster for cough and fever. Patanjali has reportedly given all details of the randomised placebo-controlled clinical trials it conducted on CORONIL to the Ministry of AYUSH, who are expected to study the data and come out with their decision.

Asking industry to keep an open mind, the AYUSH sector has pointed out that if doctors are willing to administer investigational medicines like HCQ, umifenovir, favipiravir and remdesivir, then why shouldn’t traditional medicines be allowed the same leeway? While it is true that these and other medicines are being repurposed to COVID-19, the difference is the strict oversight mechanisms governing clinical trials. For instance, Glenmark’s pack of favipiravir has an informed consent form which the prescribing doctor has to first explain to the patient before it is filled, submitted before the patient starts on the course. All patients will be observed and patient data will be analysed and submitted for review to the regulatory body.

This review process allows changes in treatment protocols so that future patients can benefit. But Patanjali’s immunity booster is an OTC medication. Can patients be followed up? What are the signs, the endpoints to show immunity was boosted and cure was due to CORONIL? However, if indeed Patanjali’s CORONIL trial passes regulatory muster and is published in peer-reviewed journals, it will mark an important coming of age milestone for India’s AYUSH sector.

But, the crux of the issue is to separate the hype from the hope. In India, the Council for Scientific & Industrial Research (CSIR) identified 25 drugs for repurposing for COVID-19, of which two have reached phase III clinical trials: Cipla will take Favipiravir forward while Umifenovir will be made and marketed by Medizest Pharmaceuticals. Sun Pharma, with ICGEB New Delhi and CSIR IIIM Jammu with support by CSIR and DBT, was given permission to conduct a clinical trial for the first phytopharmaceutical or plant-based drug AQCH to treat COVID-19 patients.

“The repurposing priorities were based on many different parameters such as the IP status, druggability index, availability of APIs etc.,” says Dr Shekhar Mande, DG-CSIR.

However, experts have cautioned that there are bound to be efforts where corners are cut in the race to the finish line, only to be discredited as the research cannot stand up to peer review. Or worse, a “wonder drug/miracle cure” makes it from lab to clinic only to fall short of expectations, as it does not give the same results in vivo as in vitro. This is tragic not just for the potential loss of lives, time, effort and resources, but also because it discredits drug discovery and development efforts. And unfortunately, the people and the process of drug development and discovery.

Giving his assurances on this issue, Mande emphasised that there will be no compromise on the standards of ethics or that of research practices. “The best practices that are used around the world, are being followed strictly in CSIR also. The checks and balances are similar to best practices being followed in all other places.”

India’s rising COVID-19 cases need all the help they can get, be it allopathy or AYUSH. The caution is not to discredit any particular approach but merely to see what is safest for patients. Good science must win over popular appeal.