Rajneesh Bhandari , Angel Investor, Founder NeuroEquilibrium
“The charm of history and its enigmatic lesson consist in the fact that, from age to age, nothing changes and yet everything is completely different.” – Aldous Huxley
Last week the Pfizer/ BioNTech mRNA vaccine was approved within 11 months of the discovery of the COVID 19 virus. Pfizer vaccine is the most rapid vaccine deployment in history completing all the mandatory stages (the Russian and Chinese vaccines have been approved before Phase III trials).
The history of vaccine development has been chequered and not very encouraging. It took 26 years to develop a vaccine for the human papillomavirus (for cervical cancer ) and 25 years for a vaccine for rotavirus( against gastroenteritis).Thirty-five million people have died of AIDS in the last 40 years. Since 1987, 30 vaccine candidates have been tested in human clinical trials, but no candidate has cleared the phase III trial to date. More than $500 million is spent globally on the development of the AIDS vaccine annually.Malaria affects 400 million people annually resulting in 2 million deaths. Over $100 million is spent annually on vaccine research, but there is no vaccine in sight. There is no vaccine against other coronaviruses like SARS and MERS.
So how (and why) is it that within 100 days of the discovery of COVID 19, there were 45 vaccines in development? How was it possible for the first vaccine – from RNA sequencing to injecting a volunteer – be done in just 63 Days (Moderna)?
Today we have over 321 vaccine candidates in various stages of development with 40 vaccine candidates in human clinical trials, 9 in phase III trials, and one already approved.
There are broadly four steps of vaccine development and deployment
a) Understanding the structure of the virus
b) Understanding the interactions of the virus in the human body to find a suitable vaccine candidate
c) Clinical trials and regulatory approval
d) Large scale production and distribution
Traditionally, upon identification of a novel virus, the virus had to be taken apart piece by piece to understand its different components. A decade ago, this used to take 1 to 2 years.
There have been tremendous advancements in genome sequencing in the last decade. As an example, the cost of human genome sequencing has dropped from USD 100 million in 2001 to just $500 in 2020 and will probably drop to $100 in 2021. With the advanced technologies now available, China and France were able to decode the virus in less than a week.
The second step is to identify which elements of the virus trigger an immune response, purify that agent (epitopes), and test it on animals. A decade ago, this process would have taken another 1 to 2 years, sometimes more than five years.
Various technology breakthroughs along with the use of computational models and AI have helped shrink these steps to weeks if not days (Moderna vaccine candidate was developed within 2 days of the publishing of the virus structure!!!)
The third and most crucial step is clinical trials. Like all medicines, vaccines go to clinical trials after they are tested in experimental animals. Based on typical FDA processes, the time for clinical trials could be more than ten years, as the regulatory body requires vaccines to undergo at least three phases of clinical trials before applying for approval.
Phase I is to assess the safety of the vaccine candidate. A few healthy volunteers (between 20 to 80) receive the vaccine.
In phase II, the vaccine is given to a larger number, and markers like antibodies are used to see if the vaccine has the potential for a protective immune response.
In phase III, several thousand participants are divided into two groups. One group receives the vaccine, and the other receives a placebo. This phase aims to compare the two groups and establish if the vaccine is effective at preventing the disease. Phase III trial is the most time-consuming step because researchers have to wait for enough participants to be exposed to a virus naturally. One cannot compress time when one is relying on a natural exposure to occur.
Pfizer completed the phase III trial when there were 170 cases of the disease in its trial of around 43,000 volunteers, of which 162 were observed in the placebo group and 8 in the vaccine group.
Historically, from Phase I clinical trials, around 90% of vaccine candidates fail to make it to final approval, and from Phase III, 25% fail. The investment by a manufacturer in a vaccine candidate typically exceeds US$1 billion. In the case of drugs, the average cost of bringing a drug to market is $2.5 billion, with only a 10% success rate after phase I.
How can we find a solution to the paradox of having a vaccine candidate within 42 days, which eventually gives 95% efficacy but requires a clinical trial extending ten months while millions die?
Pfizer and Moderna have used a novel mRNA technology for their vaccines, which are faster to develop. This new technology does not require a protein or weakened pathogens for the vaccine. The genetic material mRNA is easy to make in a laboratory, and manufacturing an mRNA vaccine rather than a protein can save months. This new technology is like writing a software upgrade instead of finding new hardware each time. It offers various advantages, including multiple mRNAs for multiple variants of the virus in a single vaccine. It does not require dedicated cell-cultures or fermentation-based manufacturing processes for each kind of vaccine.
The fourth step is rapid manufacturing and deployment. The manufacturing of various COVID vaccine candidates is already underway before clinical trials have concluded. A tremendous amount of risk capital has been available for this to happen.
Pfizer will be ready with 50 million vaccine doses this year and produce more than 1.3 billion doses in 2021. Moderna plans to make 500 million doses in 2021. AstraZeneca would be making 850 million doses annually of this vaccine, of which about 400 million would be available to India. India already manufactures and supplies the bulk of the world’s vaccines.
To summarize, rapid advances in multiple technologies will lead to even faster development of drugs and vaccines in the future. Today drug and vaccine development has moved from cell culture and fermentation processes to computational models, data analytics and AI.
The irony is that the global pharma companies and scientific institutions may still not have much interest in the pandemics of the developing world including TB, Malaria, AIDS etc and these diseases will continue to kill millions despite the technological advances.
As Yuval says in his book Homo Deus (published in 2016 ), “While we cannot be certain that some new outbreak or an unknown flu strain won’t sweep across the globe and kill millions, we will not regard this as an inevitable natural calamity. Rather, we will see it as an inexcusable human failure and demand the heads of those responsible”.
Post Star needs your voice. We welcome your on-topic commentary, criticism and expertise.
