Moderna's COVID-19 vaccine aces phase 3, with no severe cases

Moderna’s phase 3 COVID-19 vaccine has hit its primary endpoint with efficacy of 94.5%. Ninety cases of COVID-19, including all 11 severe cases seen so far, happened in the placebo cohort, versus five cases among people who received mRNA-1273.

One week ago, Pfizer and BioNTech showed COVID-19 vaccines could work better than people dared to hope, linking their candidate to a more than 90% reduction in cases. Now, Moderna has confirmed the effectiveness of mRNA COVID-19 vaccines, while still leaving certain questions unanswered, with top-line results that suggest it may meet or exceed the high bar set by Pfizer and BioNTech. 

“These results are very strong and suggest mRNA-based technologies can deliver so far for COVID-19 protection. Indeed, PFE and now MRNA both have very high end efficacy,” analysts at Jefferies wrote in a note to investors.

Moderna’s statement contains details absent from the press release put out by Pfizer and BioNTech, notably the numbers of severe COVID-19 cases in each arm. Five participants who received mRNA-1273 developed COVID-19, but none of those cases were severe. There were 11 cases of severe disease in the placebo cohort, as well as 79 infections that manifested in milder symptoms. 

The secondary endpoint classed patients as having severe COVID-19 if they had clinical signs of severe systemic illness, such as blood oxygen of 93% or less, suffered respiratory failure or distress, or experienced significant acute renal, hepatic or neurologic dysfunction. If mRNA-1273 significantly reduces those outcomes, its vaccine could dramatically lessen the negative impact of COVID-19 even if the coronavirus continues to spread and infect people.

For now, Moderna is the only company to share details of the effect of a vaccine on severe cases. It is possible that the effect will be replicated by other vaccines as Pfizer and the other companies that are yet to share top-line data publish more results. 

Moderna said 17% of COVID-19 cases seen across both arms of the trial involved people aged 65 years or older. The protocol called for people aged 65 years or older and younger people deemed to be at increased risk to make up 25% to 40% of the study population. Moderna is yet to say how the 15 cases seen in older adults were split across the two arms. It is possible COVID-19 vaccines will be less effective in older people, but Moderna said efficacy appears consistent across subgroups. 

On the safety front, Moderna said most of the grade 3 events occurred after the second dose. At that time, 9.7% of subjects experienced fatigue, 8.9% suffered muscle pain and 5.2% reported joint pain. Smaller numbers of participants experienced grade 3 headache, pain or redness at the injection site. The most common grade 3 event after the first dose was injection site pain at 2.7%. The preliminary analysis suggests safety and tolerability are consistent across subgroups. 

Moderna plans to use the data to seek FDA emergency use authorization (EUA) “in the coming weeks.” By the time of the filing, Moderna expects to have the final analysis based on 151 COVID-19 cases and a median follow-up of two months, thereby satisfying the FDA’s EUA requirements. Getting an EUA will tee Moderna up to ship 20 million doses in the U.S. by the end of the year, before going on to sell 500 million to 1 billion shots globally in 2021. 

Minutes before releasing the data, Moderna issued a statement about the storage requirements of mRNA-1273. According to Moderna, the vaccine is stable at 2 degrees Celsius to 8 degrees Celsius, standard refrigeration, for 30 days. That beats Moderna’s earlier estimate of seven days and the five days that the Pfizer vaccine can spend at refrigerator temperatures.

The data shared by Moderna so far leave some questions unanswered. Notably, the durability of the vaccine, and all other COVID-19 prophylactics, will only become clear in the coming months. That will shape the effectiveness of immunization campaigns. Further details of the efficacy of mRNA-1273 in subpopulations are needed, too.

More broadly, while the data drops by Moderna and Pfizer validate mRNA COVID-19 vaccines, it remains unclear whether other platforms will be similarly effective. That question will start to be answered when AstraZeneca shares data on its viral vector vaccine, which could happen by the end of 2020. 

Shares in Moderna rose 16% following the release of the data. BioNTech fell 7%.