By Amit Kumar, Ph.D., CEO of Anixa Biosciences
July 10, 2020
Vaccine or Therapeutics
The ongoing Covid-19 pandemic is a major public health concern with corresponding economic disruptions. Our industry has honorably stepped up to develop both vaccines and therapeutics to fight the SARS-CoV-2 virus. An unprecedented collective effort has included participation from the private sector, governments and academia. However, despite constant media coverage of the pandemic, the key challenges and considerations regarding the development of both vaccines and therapeutics remain misunderstood. This article lays out some of the important concerns in vaccine development and timelines and contrasts that with therapeutics development and timelines.
An effective and safe vaccine that is easy to manufacture, distribute and administer would be an ideal tool to battle the pandemic. While roughly 170 candidates are in different stages of development, and we are cautiously optimistic that a vaccine could soon be available, there remain several issues and challenges. A prophylactic vaccine is administered to reduce or eliminate the risk of disease. A Covid-19 vaccine would be administered to nearly 350 million individuals in the U.S. and nearly 8 billion people worldwide. Because it is administered to healthy people, the most important figure of merit is the safety of the vaccine. People erroneously believe efficacy is most important. While we would all like a vaccine that is nearly 100% effective, a vaccine is still valuable even if it is only 30% effective, if it is safe. A clear example is the flu vaccine, which is often 20% to 40% effective, but still valuable for society since it is safe. The most common side-effect is temporary pain at the site of injection, and some people suffer from a very mild fever and muscle aches. The incidence of Guillan-Barre Syndrome is about 1 in a million (one one-thousandth of 1%, almost a negligible number).
A Covid-19 vaccine that causes serious side effects in only 1% of patients could be a disaster, as it might cause problems for 80 million people. This type of vaccine, if it has serious side effects would overwhelm the healthcare infrastructure of the world and would do more damage than the pandemic itself. This concern is the reason vaccine trials take so long and involve monitoring participants over a significant time span to make sure there are no long-term side effects. In the case of this pandemic, our world is expecting a vaccine by the end of the year or early in 2021.
Despite the many vaccine candidates in development, only about 20 are now involved in clinical trials. To have a vaccine by early 2021, it will come from these early candidates. Any vaccine not in clinical trials today will not reach the market by the first half of 2021. Even among the early clinical candidates, everything must go perfectly to have a successful vaccine by early next year. Most importantly, we will only have a few months of safety evaluation for the early 2021 deadline, and the U.S. Food and Drug Administration (FDA) must decide to accept the short evaluation period for safety analysis.
While safety is the most important characteristic, efficacy is also vital. Preclinical and early clinical data for several vaccine candidates show antibody response in healthy volunteers, but we do not know if that response confers immunity, how strong it is or, how long it lasts. We must answer these questions in Phase 3 trials and post-approval monitoring (Phase 4). Also, we do not know if immune responses will occur in the highest risk demographic, the elderly. None of the vaccine candidates have yet been tried on the aged or individuals with underlying conditions. In our favor, there have been no credible reports of re-infection in recovered Covid-19 patients. If a patient falls ill again after recovering from a full-blown, symptomatic infection, it suggests that a vaccine will fail to induce a sufficient immune response to protect against the virus. We may end up with either nothing or a vaccine administered annually like the flu vaccine.
I will not discuss in detail the ethical or logistical issues related to vaccination, but they are important to keep in mind. Producing significant quantities of a vaccine poses a challenge. Distribution presents an even bigger issue, especially in developing nations, and if a vaccine requires refrigeration or other special handling. And finally, there are questions about the price of a vaccine and ethical concerns regarding which patients and countries get vaccinated first.
Unlike vaccines, Covid-19 therapies would be administered only to infected patients showing symptoms. This patient population represents a fraction relative to the number of patients that require vaccination, and greater side effects can be tolerated. Side effects in 1% of the world’s 8 billion vaccinated people might be unacceptable, but even more dramatic side effects in 10% of sick people might only result in problems for a few thousand people, based on current rates of infection. For example, at the current time, we have cumulatively had roughly 3 million confirmed infections in the U.S. Of those 3 million, many have already recovered, have died or are asymptomatic. Consequently, of the 3 million confirmed cases, there are probably only a few tens of thousands that need a therapeutic. Therefore, even with a rapidly increasing symptomatic population, logistical issues (manufacturing, distribution, cost, etc.) for a therapeutic are much more addressable than for a vaccine.
The first group of therapeutics tried against Covid-19 were drugs already in development, or in some cases approved for other diseases. This strategy made sense due to the need to quickly find effective treatments. To date, only remdesivir has demonstrated efficacy in properly conducted clinical trials, though it demonstrated only modest benefits to hospitalized patients and did not appear to improve mortality. Furthermore, remdesivir requires intravenous infusion. There are other candidates in clinical trials, and we will shortly see how they perform.
Remdesivir and many other repurposed candidates have been thrown at SARS-CoV-2, but a better strategy might be to develop new drug candidates specifically designed to inhibit the molecular machinery of the virus. In five months of studying the virus, we not only have the full RNA sequence, but have also identified important enzymes and structural proteins, and even have crystal structures for many of these proteins.
The ideal Covid-19 drug candidate can be formulated as an inexpensive pill. An effective therapy such as this would potentially make Covid-19 similar to the flu or even a mild cold in terms of severity and treatment.
Until we have a therapy or vaccine, we, as a society and as individuals, must make some decisions. Our policy makers and leaders have a very difficult task. While we all want the economy to open, there must be a balance between further infections and economic resurgence. On one extreme, we can minimize infections, but we may destroy the economy and cause other second or third order effects. On the other extreme, we can reopen the economy as completely as possible, but run the risk of a resurgence in infection rates. Society must decide where that balance lies. As individuals, we must make the same choice. Some of us have no choice as we may be in essential industries and must work and perform other tasks, such as going to the grocery store. However, some elective activities that may not be necessary could be postponed. Regardless of whether we are required to interact with people and crowds or whether we chose to, if we remember the three initials H-M-D (Hygiene, Masks, Distancing), we can dramatically reduce the risk of infection.
Finally, there are those that have indicated that an effective vaccine or therapy by early 2021 has been priced into the capital markets. If we do not have an effective vaccine or therapeutic by that time, and the infection rate continues to rise, the stock market could be dramatically damaged.
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