With no end to the Covid-19 pandemic in sight, the only solution to liberate us from SARS-CoV2, the novel coronavirus, appears to be a vaccine. Creating a vaccine, however, is no easy feat. The record time for developing a vaccine, which resulted in an effective vaccine for mumps, is four years. Ordinarily, vaccine formulation and clinical trials, proving it efficacious, take 10-15 years. Operation Warp Speed is hoping to truncate this process to under a year.
The typical process for producing a vaccine, or any medication, is meticulous and extensive. It begins with research and development as well as capital procurement. These steps, often done in tandem, can take years, depending on the technology behind drug innovation and investor interest. When a drug is believed to treat its intended affliction, preclinical trials begin on animals. This is primarily to assess safety but also to see what response the medication induces. If all goes well, human clinical trials commence and occur in three phases. The first phase is on a small subject group, typically fewer than 50 people, and focuses on safety. This typically takes several months. The second phase tests the medication on hundreds of people and focuses on a physiologic response, side effects, and, again, safety. It also gauges correct dosing. Phase two can last a few months to a year. The third and last phase is a wide-spread trial across thousands of subjects that compares the vaccine or treatment in question to a placebo. Typically, the length of time for a Phase III trial ranges between one to three years. Finally, the results are sent to the FDA for review and, hopefully, approval with licensing. This process may seem tedious, but is imperative. It’s important to note that most medications do not pass all the phases of clinical trials to become FDA-approved. In fact, likelihood of drug approval has been estimated at less than 20%.
So, how is this process different? Operation Warp Speed (OWS) is an initiative by the U.S. government to vaccinate 300 million Americans against Covid-19 by next January. It is attempting to accomplish this by pumping money into the race – over $12 billion – to develop, procure, manufacture and distribute vaccines. In addition, OWS has standardized protocols for biotech companies to follow, rather than the norm of companies creating their own. Clinical trials can be accelerated, and protocols have been adjusted. In this instance, many preclinical and Phase I clinical trials are being done simultaneously, and some Phase II and III clinical trials have been combined. In addition, manufacturing of vaccines has already begun, so if one of the candidates ultimately proves to be effective, distribution can begin without delay. U.S. funding has gone to 12 pharmaceutical companies, including two American companies – Moderna and Pfizer.
Currently, there are forty vaccines being tested in multiple human trials worldwide. Nine vaccines are in Phase III. Two of these vaccine candidates are by the two American biotech firms. Moderna was the first pharmaceutical company to initiate clinical trials in March, doing so, ironically, in the same week Covid was labeled a pandemic. China and Russia have already begun allowing some vaccine use, although the respective pharma companies in developing vaccines in those countries are only initiating the third phase of clinical trials. China has permitted that its military be vaccinated with the experimental preparation by CanSino Biologics, partnered with Beijing Institute of Biotechnology. Russia approved its vaccine, developed by Gamaleya Institute, for the general population, leading to many questions regarding safety. The U.S. maintains higher standards than most countries for drug safety and efficacy through FDA regulations. However, this race to find a Covid vaccine is unprecedented and the fast-tracking of testing is worrisome. Even if these vaccines do prove to induce an immune response that develops antibodies to SARS-CoV2, it is unknown how long it will be effective for and what all the side effects may be.
Moderna has received $1 billion from the U.S. government and currently has 30,000 people enrolled in a Phase III clinical trial across the country. If vaccine efficacy is proven, the firm will receive another $1.5 billion from the government in exchange for 100 million doses. Pfizer has partnered with two foreign firms, BioNTech in Germany and Fosun Pharma in China, and was originally testing two different vaccines. Both vaccines showed to be effective in early trials, but one had fewer side effects. That vaccine was selected to continue to a combined Phase II and III with over 30,000 subjects enrolled in different countries. Pfizer will receive $1.9 billion if its vaccine is approved, in exchange for 100 million doses. Both Moderna and Pfizer are using re-engineered messenger RNA (mRNA). mRNA are molecules that relay genetic instructions from DNA to the cell’s protein-making machinery. The technology sends synthetic mRNA into cells in order to cause some type of response – in the case of Moderna’s SARS-COV2 vaccine, mRNA-1273 – an immune response that causes the body to develop antibodies against the virus.
The next month may be telling if there will be a vaccine this winter. In the meantime, wash your hands, wear your mask, and stay six feet apart.