Gates Package — page 1174

reen to see which should go into human trials first. PANDEMIC I - THE FIRST MODERN PANDEMIC There is a class of drugs called antivirals, which keep the virus from functioning or reproducing. The drug industry has created amazing antivirals to help people with HIV, although it took decades to build up the large library of very effective triple drug therapies. For the novel coronavirus, the leading drug candidate in this category is Remdesivir from Gilead, which is in trials now. It was created for Ebola. If it proves to have benefits, then the manufacturing will have to be scaled up dramatically. The foundation recently asked drug companies to provide access to their pipeline of developed antiviral drugs so researchers funded by the Therapeutics Accelerator can run a screen to see which should go into human trials first. The drug companies all responded very quickly, so there is a long list of antivirals being screened. Another class of drugs works by changing how the human body reacts to the virus. Hydroxychloroquine is in this group. The foundation is funding a trial that will give an indication of whether it works on COVID by the end of May. It appears the benefits will be modest at best. Another type of drug that changes the way a human reacts to a virus is called an immune system modulator. These drugs would be most helpful for late-stage serious disease. All of the companies that work in this area are doing everything they can to help with trials. VACCINES Vaccines have saved more lives than any other tool in history. Smallpox, which used to kill millions of people every year, was eradicated with a vaccine. New vaccines have played a key role in reducing childhood deaths from 10 million per year in 2000 to fewer than 5 million per year today. Short of a miracle treatment, which we can't count on, the only way to return the world to where it was before COVID showed up is a highly effective vaccine that prevents the disease. Unfortunately, the typical development time for a vaccine against a new disease is over five years. This is broken down into: a) making the candidate vaccine; b) testing it in animals; c) safety testing in small numbers of people (this is known as phase 1); d) safety and efficacy testing in medium numbers (phase 2); e) safety and efficacy testing in large numbers (phase 3); and f) final regulatory approval and building manufacturing while registering the vaccine in every country. Researchers can save time by compressing the clinical safety/efficacy phases while conducting animal tests and building manufacturing capacity in parallel. Even so, no one knows in advance which vaccine approach will work, so a number of them need to be funded so they can advance at full speed. Many of the vaccine approaches will fail because they won't generate a strong enough immune response to provide protection. Scientists will get a sense of this within three months of testing in humans by looking at the antibody generation. Of particular interest is whether the vaccine will protect older people, whose immune systems don't respond as well to vaccines. The issue of safety is obviously very important. Regulators are very stringent about safety, to avoid side effects and also to protect the reputation of vaccines broadly, since if one has significant problems, people will become more hesitant to take any vaccines. Regulators worldwide will have to work together to decide how large the safety database needs to be to approve a COVID vaccine.