January 12, 2021
Steve Seedhouse, Raymond James biotechnology analyst, discusses the Moderna and Pfizer vaccines’ trial results, manufacturing plans and rollout strategies.
To read the full article, see the Investment Strategy Quarterly publication linked below.
In December, the FDA granted emergency use authorizations (EUAs) in the United States for two COVID-19 vaccines in people over 16 years old (Pfizer vaccine) and people over 18 years old (Moderna vaccine). Both vaccines are currently being distributed and administered by priority, starting with healthcare personnel and long-term care facility residents.
Moderna’s vaccine was 94.1% efficacious in a 30,000-patient Phase 3 study; Pfizer’s was 95% efficacious in a ~44,000-patient study. Importantly, severe COVID-19 cases were also reduced (0 in vaccine vs. 30 in placebo group for Moderna, 1 vs. 9 for Pfizer). Generally speaking, this level of efficacy exceeded most experts’ expectations. For context, vaccines for polio (99%), measles (97%), and rubella (>95%) are slightly more effective, but chickenpox (92%) and mumps (88%) are actually less effective. In any given year, seasonal flu vaccines are 40% to 60% effective.
There are no concerning acute safety signals in the completed studies, although detailed safety data from the large Phase 3 studies have not been published. However, the speed of development and high attack rate (the rate at which people got COVID-19 in the Phase 3 study, leading to quick completion of primary efficacy analysis) mean long-term safety data are simply not available. No patient that enrolled in any study phase is more than one year out from their first vaccination. Based on the good acute safety profile, the large nature of the Phase 3 studies, and historical knowledge of safety for other vaccines (very rarely, if ever, do safety issues emerge beyond about two months post vaccination), we do not expect any safety issues. It should be noted that there are tolerability side effects of these vaccines such as fatigue, chills, muscle pain, fever and more.
Although no vaccine has previously been developed in less than a year, ~95% efficacy and clean safety profiles were demonstrated in gold standard, placebo-controlled, large Phase 3 trials. We expect public health officials, the FDA, CDC, and community physicians will be major advocates for widespread vaccination in virtually everyone except children (until more data are available).
Manufacturing and distribution
It will be very important to closely monitor manufacturing and distribution to track whether Moderna and Pfizer are hitting their targets in 2020 and 2021. Moderna expects 20 million doses ready to ship in the U.S. in 2020 and 500 million to 1 billion doses (250-500 million people) in 2021. Operation Warp Speed in the U.S. has already secured the first 100 million doses for $1.5 billion, expected to be delivered before the end of the first quarter. Separately, Pfizer expects current production capacity of about 20 million doses per month to provide about 50 million total doses for worldwide distribution in 2020 and 1.3 billion doses (650 million people) in 2021, comprising:
- 200 million doses for the European Union in 2020-2021 + 100 million option
- 120 million doses for Japan, first half of 2021
- 100 million doses for the U.S. 2020-2021 (by March) + 500 million option
- 30 million doses for the U.K. in 2020-2021
- Undisclosed number for Canada, plus 22 preliminary contracts (term sheets) and another 30 countries and supranational organizations in discussion.
Long-term storage of Pfizer’s vaccine requires -80°C freezers (commercially available freezers commonly used in research labs and hospitals). Vaccine vials can be stored in this way for about six months. However, Pfizer’s vaccine can be stored or shipped on dry ice for up to 15 days and then refrigerated up to five days at the points of use. The compressed gas industry indicates it expects sufficient dry ice supply to meet the demand, and FedEx and UPS should be able to handle vaccine delivery with no problem. Moderna’s vaccine is even easier to store, requiring -20°C long-term storage (standard kitchen freezer) and refrigeration up to 30 days, or room temperature up to 12 hours.
On December 1, the CDC’s Advisory Committee on Immunization Practices (ACIP) met to discuss priority for vaccine allocation upon EUA. The committee members were asked to vote on a motion for the following proposed interim recommendation:
“When a COVID-19 vaccine is authorized by FDA and recommended by ACIP, vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a) should be offered to both 1) health care personnel and 2) residents of long-term care facilities.”
The motion passed 13 to 1 in favor of the interim recommendation. The one dissenting vote seemed to be based on not having access to Phase 3 data and lack of data specifically pertaining to use in long-term care facility residents – a reasonable dissent, in our view, but overwhelmingly outnumbered.
There are about 21 million healthcare personnel and 3 million residents of long-term care facilities in the U.S., so we expect advancement to Phase 1b, essential workers, in the first quarter of 2021. The ACIP identified about 87 million essential workers in the U.S. including teachers, firefighters, police, food service and agriculture workers, transportation, and more. Phase 1c would comprise people with risk factors and people over 65 years old, followed in Phase 2 by healthy adults.
“Herd immunity” and a full return to normal within the U.S. are expected by the second half of 2021, so long as vaccine manufacturers hit their target dose goals and the public sufficiently uses the vaccine.
All expressions of opinion reflect the judgment of the author and are subject to change.