Therapies and Vaccines
The Milken Institute has been tracking the number of institutions working on therapies and vaccines in different stages of development all over the world: the current estimate is 58 treatment therapies and 43 vaccines.1
Regeneron shared their two-pronged approach to dealing with Covid-19. The first approach is to leverage what is already “on the shelf.” For example, Kevzara is an already approved drug that is used to treat rheumatoid arthritis by creating a fully human antibody that blocks a receptor called cytokine interleukin-6 that causes inflammation. Regeneron shared that this drug has been used in China in an “uncontrolled” approach, but has had some encouraging results. Regeneron has initiated a phase 2/3 trial to properly test the efficacy of this drug. If successful, it would be used to reduce lung inflammation arising from Covid-19 for the critically ill.
The second approach is to recreate antibodies that one would ordinarily get from a vaccine. Regeneron has isolated virus-neutralizing, fully human antibodies that have been developed in their Velocimmune mice; these antibodies are then manufactured through recombinant DNA. This approach was used to fight Ebola successfully in the Congo. Regeneron expects to begin testing in June and producing the antibodies on a larger scale in late summer.
There is also considerable work being done on vaccines using more innovative biotechnology. The National Institute of Health dosed its first participant in a Phase 1 study with Moderna’s messengerRNA-1273 vaccine (mRNA) on March 16. In this new class of medicine, the mRNA is injected in the muscle to instruct human cells to produce the virus protein which will, in turn, teach the body to make a productive antibody, thereby mimicking a natural infection. Phase 1 is expected to enroll 45 healthy adult volunteers between the ages of 18 to 55 over approximately six weeks. The goal of the Phase 1 study is to gather data on the safety and immunogenicity (ability of the vaccine to induce an immune response in participants). If Phase 1 and the subsequent Phase 2 demonstrate safety and good immunogenicity, Moderna is optimistic that they may be able to provide vaccinations by the fall of 2020 for emergency personnel, doctors, nurses, and others on the front line of defense against the pandemic. Broader-based availability would be in the fall of 2021.
Interestingly, if the virus mutates, Moderna believes that they can easily adapt their vaccine to the new genetic sequence of the virus.
Inovio is working on a similar concept, but based on a DNA vaccine rather than an mRNA-based one. They expect to start clinical trials in a few weeks. However, as pointed out by Dr. Tebas, Phase 1 trials look at safety and immunogenicity, but Phase 3 trials measure efficacy of the vaccine over a larger group of people to see if the vaccine actually prevents people from getting Covid-19. He reiterated the time table suggested by other speakers: Phase 1 in multiple organizations has already started or is starting soon, Phase 2 with larger trials possibly including high-risk populations and first responders, and Phase 3 expected in the fall of 2020.
One of the very interesting points raised by Leonard Schleifer of Regeneron was one of serological testing, which is used to determine who has already had an infection. On March 17, a team of scientists, led by Dr. Florian Krammer of the Icahn School of Medicine at Mount Sinai in New York, published a paper showing how their test can measure the level of antibodies in a patient.2 This test can be used to identify recovered patients who could then donate their SARS-CoV-2 antibody-rich serum to help treat critically ill patients. According to Dr. Krammer, another key application of these tests would be to identify people who have likely developed immunity to the virus, especially among hospital staff. These virus-resistant staff could then take on front-line jobs during the pandemic by delivering care to patients with minimal risk to themselves or others.
One of the most frequently asked questions is the efficacy of chloroquine or hydro chloroquine combined with the antibiotic azithromycin in treating the virus. The inquiry is the result of a mid-January report from China translated into English with no data, and a subsequent report by a group of French doctors with 36 patients. According to Dr. Barry Bloom, these drugs are currently being investigated in a more systematic scientific manner, but the current data is more anecdotal. Dr. Leonard Schleifer, M.D., also cautioned our clients “not to jump on late night infomercial equivalents,” referring to therapies that have not yet been rigorously tested.
While the light at the end of the therapies and vaccines tunnel is not shining brightly, it is still visible. The amount of talent and resources devoted to addressing both the virus and the disease is immense, and it is hard to imagine that these efforts, as discussed by our panel of experts, will not yield any successful results in the near future. We believe there is room for a modicum of optimism.