Getting To Develop A Vaccine
VACCINE SAND BIOLOGICAL PRODUCTS ARE SEEN AS EXTENSION OF PHARMACEUTICALS. THE DRUGS AND COSMETICS ACT ALSO COVERS VACCINES. A LOOK INTO THE REGULATORY PROCESS
issues of the developed world. They acquire small vaccine makers with promising candidates rather than investing in basic research. They are not ready to invest in research on viruses that cause outbreaks in hot and humid geographies of Africa or Asia," the executive, who did not wish to be named, says.
If Indian pure play vaccine makers used the opportunity well, the Indian pharmaceutical industry has had a bitter experience of finding new pharmaceutical drugs.
A Failed Dream
A decade ago, gazing into the sunset from the balcony of a Mumbai hotel suite, with tears rolling down his cheeks, Dr Kallam Anji Reddy said, "That day I got a call from Novo saying the rats have died. That was the end of my Bala". Bala refers to anti- diabetes molecule Balaglitazone that his company was developing.
The founder of Dr Reddy's Laboratories in 1979 was elaborating how his new drug discovery dreams had failed forever. He died in March 2013, at the age of 74. Like Ranbaxy's late Dr Parvinder Singh and Lupin's founder, late Dr Deshbandhu Gupta, Dr Reddy's dream was to invent NCEs that would convert their generic drug-making firms into original innovator companies like Pfizer, Novartis or GlaxoSmithKline selling blockbuster drugs, each with over $1 billion sales. In 1997, scientists at Dr Reddy's Laboratories in Hyderabad discovered a molecule to treat Type-2 diabetes. They named it Balaglitazone and licensed the NCE candidate to Novo Nordisk for clinical
trials. Novo discontinued the trials after the drug failed.
Ranbaxy’s plan to develop a new drug for malaria, Arterolane, also got dropped after its sponsor, Medicines for Malaria Venture, backed out in 2007 while last stage trials were on, ending the new drug dream. Indian companies like Sun Pharma, Piramal Life Sciences and Glenmark also tried to develop NCEs but could not make anything for global markets. Tata funded Advinus Therapeutics since 2005 and wanted to be big in drug research, but it was sold off in 2017 to Eurofin, a European laboratory chain . It remains to be seen if the global goodwill pharma companies are expected to generate as vaccine suppliers and the soft power it provides can be leveraged for a comeback in new drug research.
The Opportunity
In his opening remarks at the 12th BRICS Virtual Summit on November 17, Prime Minister Narendra Modi made a reference to only one industry, the pharmaceutical industry. “India can be a force multiplier for the post- Covid economy. And can contribute strongly to global value chains. We proved this during Covid, when we were able to deliver essential medicines to over 150 countries due to the capability of the Indian pharma industry," Modi told the heads of Brazil, Russia, China and South Africa at the Summit.
With none other than the prime minister its ambassador, the goodwill that is being generated for the Indian pharmaceutical industry is formidable. Further, most companies pursuing vaccine dreams other than leading pure play vaccine makers are established pharmaceutical companies like Zydus Cadila, Dr Reddy's, Aurobindo, etc. The demand for Indian medicines and vaccines during the pandemic has again increased the demand for Indian products in most parts of the developing world. Bangladesh has already made a formal request for Covid-19 vaccine supplies, and the Central government has already said that their preference will be to supply to other neighbouring countries like Bhutan and Nepal.
Pharma companies can even leverage the vaccine opportunity to get back into big game of drug development and research as managing Covid-19 in future will require new treatment protocols and new drugs. That also may spur the boat that India has missed so far – the world of NCE research. As of now, it may seem a distant prospect, as the world is now concentrating on vaccines and repurposed drugs, but that is also going to be a big opportunity.
Experts say the next big leap for pharmaceutical companies could come from drugs that are developed using new, quicker ways that medical research sector has learnt to adopt while attempting to find a cure for Covid-19 and give protection from Covid-19. Global advisory
Boston Consulting Group ( BCG) lists three elements that will redefine global clinical development which Indian pharmaceutical firms can adopt. The first is virtual first approaches, the second is real world evidence and the third is new ways of working. Virtual first is about conducting virtual clinical trials, including remote physician consultations, secure drop- shipping and medication tracking and wearable patient devices and apps to track clinical changes. US and European drug regulators have even issued guidance on such trials. The real world evidence is a way to test new treatments in weeks or months rather than multiyear timelines of traditional observational studies. The new ways of working include agile principles, regulatory flexibility, new trial designs, integrated evidence generation strategies, BCG experts say in an online blog. Covid-19 has given an opportunity to the Indian pharmaceutical industry to align itself with global clinical developments. With help from the government, it is for the Indian pharmaceutical industry to take learnings from vaccines to NCEs.
The vaccine presence will definitely help Zydus Cadila. The company already has to its credit India's first new chemical drug Lipaglyn (Saroglitazar) that can simultaneously control cholesterol and glucose levels. It is from the same 'first in class' drugs that Dr Reddy was trying to develop. But that is yet to sell in big markets like the US and Europe, though trials are on in the US for fatty liver and Hypertriglyceridemia. The Zydus Research Centre in Ahmedabad is a 4,75,000- square feet facility that employs 400- 500 scientists. Zydus has about 10 NCEs and new biological entities in different stages of development. Its decade-long investment in vaccine research has also started bearing fruit. With over 300- 500 dedicated scientists, the vaccine team of Zydus has developed India’s first vaccine for H1N1, besides multiple vaccines for infectious diseases like rabies, Hepatitis B, measles, mumps, rubella, varicella, influenza and typhoid fever.
Consider this. In end September, Swiss drug major Roche acquired a small UK biotech, ‘Inflazome’, for an upfront payment of €380 million, with promise of more money as and when it is able to develop new drugs. The company researches on a niche science, development of ‘ inflammasome inhibitors’ or ’ NLRP3 inhibitors’. Activation
of NLRP3 inflammasome in the body is implicated in many diseases caused by chronic and uncontrolled inflammation. That is what pharmaceutical scientists are now pursuing globally to contain Covid-19. But even before Inflazome can bring a drug candidate into the trial stage, India's Zydus Cadila has done it, as one among the first in the world to develop a drug candidate with NLRP3 inhibitors.
A couple of weeks ago, Zydus filed an Investigational New Drug application requesting permission for human trials with the Indian drug controller for ' ZYIL1', an oral drug candidate that proved to be effective in pre- clinic studies in controlling inflammation in Covid-19 related diseases. Zydus has filed global patents and is planning big trials abroad. “Inflammation is one of the main areas of our NCE research,” says Pankaj Patel, Chairman, Zydus Cadila. Besides, Zydus is also one the largest global manufacturers of Hydroxychloroquine and Dexamethasone, two re-purposed low- cost drugs currently being used globally to manage Covid-19. It is also developing a repurposed biotech drug, interferon alfa, for Covid-19, which is currently undergoing trials, besides making India’s first indigenously developed antigen test for Covid-19, ’Covid Kavach Elisa’, developed by ICMR-NIV, Pune.
Many others Indian companies are also trying, but are yet to divulge details. Sun Pharma’s SPARC is work
ing on two repurposed new drugs, say sources. It is conducting clinical trials of AQCH, a plant- derived drug for treatment of Covid-19 with ICGEB, Italy. This was actually developed for dengue fever. Another is Nafamostat mesylate, which was used to treat acute pancreatitis. Mankind Pharma is conducting clinical trials of a novel formulation, ‘Niclosamide’, for treatment of Covid-19 patients in partnership with South Korean firm Daewoong Pharmaceutical Co. Biocon's psoriasis drug Itolizumab was the first new biologic therapy approved (in India) for treatment of moderate to severe Covid-19 complications.
With all its capabilities, Indian drug and vaccine manufacturing industry can be the most trustworthy partner of governments across the world. The same partnerships can work for discovering drugs for infectious diseases and future pandemics too as vaccines can help, but ultimately effective drugs are the ones that take away the fear of the illness. Indian pharmaceutical industry will find their vaccine exposure extremely helpful here.
The Future
India is already a key supplier in the global institutional sales market for vaccines. Domestic vaccine makers are now eyeing the 80 per cent high value market share currently enjoyed by MNCs, mainly the private market in developed countries and a booming health conscious middle class population in developing countries like India. “We can manufacture vaccine at much cheaper prices than any country and supply enough quantities to the world,” says Adar Poonawala, CEO of Serum Institute. But he is concerned that a robust regulatory mechanism and funding support are yet to evolve in India.
“The government should sit with the manufacturers. Scientists who have never done work in vaccines should not be the ones advising policymakers,” says Krishna Ella of Bharat Biotech. According to Ella, a supportive government strategy can help India reach leadership position on the global stage. “Everybody (every regulator) says they will solve the regulatory problem, but everybody is working independently. Had we sat together instead of CDSCO as one committee, RCGM as another, subject expert committee as a third committee, if all these committees had got together, and taken decisions together, we could have moved much faster,” says Ella. “Since the pandemic, India has created a robust regulatory and collaborative ecosystem, and partnerships between various stakeholders under the National Biopharma Mission to speed up vaccine development. We are also supporting academic and institutional research on vaccines, making 60- 65 clinical trial centers in the country on a par with any top clinical trial centres across the globe,” says Renu Swarup, Secretary, Department of Biotechnology ( DBT), Government of India. India is also going to help and train partner neighbouring countries to be part of that eco- system and clinical trials, she said at a virtual seminar on vaccine distribution.
Challenges will continue, Covid-19 has been a great learning curve for Indian companies. Right from day one, the government has proactively worked at ease of approvals for Indian companies to carry out clinical trials, enroll volunteers and get regulatory feedback. The results so far do not hint at any compromise on quality. The eagerness of India’s neighbours is proving to be a great diplomatic tool too. The goodwill generated through India’s soft power should help the country break new grounds in nearly all of Africa, parts of Asia, South America and even developed nations.