For the increasingly bloated RSV vaccine market, analysts generally conclude that the two RSV vaccines from Pfizer and GSK will dominate the market, while Moderna's newly launched mRNA vaccine mRNA-1345 (i.e. mResvia) will not occupy much market share this winter due to a variety of reasons such as insufficient commercial preparation.
However, now it seems that Moderna may face a worse situation in the future.

In the briefing document released by the FDA on December 10, a more unfavorable information for Moderna was revealed: mRNA-1345 and mRNA-1365 may even aggravate RSV virus infection, repeating the mistake of more than 60 years ago that "Pfizer vaccine not only did not alleviate the symptoms of infection, but aggravated the condition of infants and caused death." Affected by this news, Moderna's stock price also fell 9% at the close of the market on the 10th.

▍Safety issues that were foreshadowed
In July of this year, Moderna reported to the FDA the safety issues in the serum-negative clinical trial of mRNA-1345 for infants under 2 years old. (However, the company did not announce the news at the time, and the suspension of clinical news was announced in September.)

Specifically, there are serious differences between RSV infection in the vaccine group and the control group, which reminds people of the Pfizer vaccine that caused children who received the vaccine to have a symptom called vaccine-associated enhanced respiratory disease (VAERD). In VAERD, vaccinated infants will develop significantly more severe respiratory diseases in subsequent natural infections than unvaccinated infants. About 80% of such children (compared to 5% of the virus-exposed control group) were hospitalized, resulting in the death of two children at the time.

However, the company's reasons for cutting the pipeline in September did not mention safety issues. At that time, the public was very euphemistic and used reasons such as strategic and portfolio optimization.

What's more interesting is that Moderna proposed to develop the adult patient market over 18 years old in a counterintuitive way. Now it seems that it is not aimless, but it may be because it realizes that the infant market is not feasible, so it can only seek unconventional markets to try its luck.

In fact, the briefing document reveals not only the mRNA-1345 pipeline, but also another pipeline of the company, mRNA-1365.

▍ Worse mRNA-1365
Compared with mRNA-1345, which only targets RSV, mRNA-1365 is a combination therapy that can simultaneously encode RSV prefusion F glycoprotein and human metapneumovirus (hMPV) F protein. In theory, it is expected to prevent RSV and MPV infections at the same time.

However, the data given by mRNA-1365 is even more pessimistic:
Ten of the 20 infants who received the mRNA-1365 vaccine later developed symptomatic respiratory syncytial virus (RSV) infection, of which three were severe or very severe cases.

However, among the 20 infants in the control group, although 12 of them later became infected with RSV, only one had a severe or very severe case.

Then the consequences of this problem are very serious. When the problem was first reported in July, it might be explained by coincidence. After all, no similar situation appeared in the preclinical data of rats and mice. But now, the problem has come to light, and the FDA will suspend all RSV vaccines for infants and young children. Two clinical trials that Moderna had not previously disclosed information will also be suspended, which is obviously a major blow to Moderna's business.

Science expert Derek Lowe commented sharply: In his opinion, no early childhood RSV vaccine will enter clinical trials soon, let alone be approved, but they will still see what the committee's final recommendation is.

Judging from the information disclosed this time, for Moderna, the future losses may be greater. In July this year, Moderna asked David Rubinstein, founder of the Carlyle Group, a political and business tycoon, to join the board of directors to help open up sales. Now that negative information has been exposed, this effort may be in vain.

In addition, investors may worry that the company's leadership did not disclose information in a timely manner, made false statements about the reasons for the suspension of the pipeline, and deceived their superiors and subordinates. Earlier, some investors who were trapped said that it would be best to resell the rights of the mRNA vaccine + drug K. Now that Moderna's stock price has fallen so badly, some investors may even launch a proxy battle.

For the FDA, in the future, the application of RSV vaccine in infants and young children may add additional clinical requirements, or simply not allow vaccine clinical trials in infants and young children. To put it another way, this is also in line with the vane in case Robert Kennedy Jr. really takes office as HHS Secretary.

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