One week ago I discussed the announcement of preliminary results for a COVID-19 vaccine announced by Pfizer and BioNTech. Since then Moderna, a biotechnology company based in Cambridge, MA, also announced preliminary results from their phase 3 vaccine trial – showing almost 95% effectiveness in preventing the disease. This is great news. Let’s go over the company, the vaccine, and the data.
Moderna was founded in 2010 as a biotechnology company dedicated to mRNA (messenger RNA) technology. So far they have not marketed a single therapeutic or vaccine, so if they get approval for their mRNA COVID vaccine that will be their first. They developed the vaccine with a grant from the US government’s Warp Speed initiative (unlike Pfizer who had the resources to fund their own research). The development of each of these vaccines cost over two billion dollars.
Like the Pfizer vaccine, the Moderna vaccine (called mRNA-1273) is also based on mRNA technology. The mRNA is a single strand of genetic material that is copied from the DNA of a gene in the nucleus. It then travels outside the nucleus to the cytoplasm where it connects to the ribosome, which reads the genetic instructions from the mRNA in order to assemble the protein for which it codes. The concept behind an mRNA vaccine is that mRNA that codes for a viral protein is injected with carriers to get it into cells. The cells then make viral proteins from the mRNA, and those proteins provoke an immune response that will target the virus.
There are currently 17 mRNA SARS-CoV-2 vaccines in development, included the two discussed here. The advantages of mRNA vaccines are that they are considered safer than DNA vaccines, they can be targeted more specifically than whole virus vaccines, and they are safer than attenuated virus vaccines because there is no risk of infection. They can also be manufactured more quickly than other vaccine types because we have the technology to rapidly replicate mRNA. If approved, these will be the first mRNA vaccines approved by the FDA.
The company previously reported results of their Phase 1 trial, showing that the vaccine produced antibodies in healthy controls, and these antibodies are capable of neutralizing the virus. The Phase 2 trial confirmed dosing and safety. The Phase 3 trial, which is the one that tests efficacy, enrolled over 30,000 healthy volunteers, half receiving two doses of the vaccine and half getting placebo. They then followed the groups until 95 total subjects contracted COVID-19. The trial reached this endpoint more quickly than projected, simply because of the Fall surge in COVID-19 cases. They now report their preliminary results.
The vaccine group had 94.5% fewer cases of COVID-19 than the placebo group. This is slightly better than the Pfizer vaccine which reported 90% efficacy. Both results are fantastic – Fauci and other experts wanted at least 50% efficacy and were hoping for something in the range of 75%, so this exceeds even optimistic expectations. Further, the placebo group on the Moderna trial had 11 cases of severe COVID, while the vaccine group had zero. This could just be a manifestation of the fact that there were fewer cases overall in the vaccine group, but the hope is it means that even if those who are vaccinated still get the disease, it will not be severe. This, of course, will further save lives and reduce strain on hospital resources.
Both vaccines require two doses 28 days apart. This is not optimal for two reasons – it means you have to produce, distribute, and administer two doses for each person protected. This will slow down the rate of vaccinating the public. Further, generally there is lower full compliance with multi-dose vaccines. Some people will simply not show up for their second dose. A single dose, based on the Phase 1 data, still produces some antibody protection, but not the level of protection seen in the Phase 3 trial.
There is also one significant advantage to the Moderna vaccine over the Pfizer vaccine. The Pfizer vaccine needs to be stored at -70° Celsius. This is extremely cold – colder than standard and even most specialized freezers. But this is not a dealbreaker and not as bad as it may sound. The same was true of the Ebola vaccine which had to be distributed in Africa. Fortunately, dry ice will do the trick. Pfizer will be able, they say, to distribute the vaccine in dry ice containers that are good for three weeks. Longer than that will require special freezers. This is a challenge for the supply chain, but doable. Once unfrozen the vaccine will last for several days in a refrigerator, while it is being distributed. This means that a facility will have to distribute all the vaccine it is sent within a few days, and if they don’t use it in that time frame the vaccine doses are wasted.
The Moderna vaccine can be stored at -20° Celsius, which is standard freezer temperature. This will make distribution and on-site storage much easier. Also, the vaccine is good for six months at -20°C, and is good for 30 days at refrigerator temperature. This will make things much easier for the clinics and hospital distributing the vaccine. Of course, these figures are extrapolated from the data we have. In order to know for sure that the vaccine is good after 6 months frozen, you would have to freeze it for six months then test it. There obviously has not been enough time for this to happen.
None of this means that the Moderna vaccine will be used instead of the Pfizer vaccine – the two are likely to be used in a complementary fashion. First, we need to manufacture as much vaccine as quickly as possible. Now we have double (roughly) the manufacturing capability. Pfizer predicts 1.2 billion doses by the end of 2021, and Modern predicts they can make an additional 1 billion doses of their vaccine. This will get vaccine to more people quicker.
The different temperature requirements also can be used in a complementary fashion. The Pfizer vaccine can preferentially go to large population centers where the doses are likely to be used up quickly. The Moderna vaccine is better suited to rural or low population density areas where it may need to be stored for longer before use.
Both vaccines also have a good safety profile so far. They have the usual vaccine side effects such as irritation at the vaccine site, fatigue, fever, and aches. So far no serious adverse events that would doom the vaccine. The FDA wants at least two months of safety follow up for at least half of the subjects enrolled in each trial, and this will happen by the end of November. Then the FDA will review the data and consider granting an emergency use authorization (EUA). Final approval will come later after the trials are complete. This means the companies will be able to start manufacturing and distributing millions of doses by the end of the year. Significant vaccination of the general population will likely not happen until the Spring of 2021, with life returning to normal by the Winter of 2021 if all goes well.