Can Novavax convince the FDA that its vaccine deserves a chance? – The crazy fool

The last flop of clinical trial of Novavax (NASDAQ: NVAX) was not as serious as the failure announced in 2016, but it was still far from what most vaccine developers would consider a success. There is still a glimmer of hope, because Respiratory Syncytial Virus (RSV) does not look like most viruses.

Despite decades of effort, we still have no effective vaccine that prevents the virus from spreading. Was Novavax's results good enough to convince the FDA that its vaccine deserved to be approved? Here is what you need to know.

How was it?

In 2016, elderly adult patients receiving ResVax were slightly more often affected by RSV-related lower respiratory tract infections (RSR) than those receiving placebo. This is about as bad as it may be for a vaccine efficacy trial, but the company has continued with a phase 3 study for pregnant women. Investors will be happy to know that babies belonging to vaccinated mothers were less sensitive to LRTI than those who were not.

Unfortunately, the observed protection benefit was not powerful enough to convince regulators of anything good, and a larger test will almost certainly be needed to advance ResVax. Novavax has reported a 39% efficiency rate for ResVax, which may seem pretty good for the uninitiated. Unfortunately, 4,636 subjects are not numerous enough to be sure that a vaccine effectiveness rate as low as 39% will bring a benefit in the real world.

What the FDA wants to see

The primary endpoint of the Prepare study was the prevention of RSV infections severe enough to cause abnormal breathing or low circulating oxygen levels. The investigators are 97.5% sure that the ResVax efficiency rate is between -1% and 64%, which represents an extremely wide confidence interval that regulators will probably not accept.

Potential new vaccines for which no available standard can be compared need the lower end of their confidence interval to reach a level that is likely to provide a clinically significant benefit. Novavax has not specified the minimum that the FDA could look for, but we can be certain that this figure is positive.

Novavax also reported results including additional data verified from hospitalization records, suggesting that a large number of hospitalized patients with severe RSV infection were not included in the study. have not been included. By including additional data, ResVax had an efficiency rate of 41% and the investigators are 95% confident that the effectiveness of the vaccine in the real world would be between 16% and 58%. This is not a large confidence interval, but you could probably say that a 16% effective prevention vaccine has a clinically significant benefit.

How much will it cost?

Unfortunately, the FDA is rarely willing to change the rules so that millions of expectant mothers receive unnecessary vaccines. This means that Novavax will need to conduct a new study with ResVax, which includes a definition of "clinically significant" RSV infections, which will give statisticians more knowledge.

If regulators do not dwell on the definitions of clinically significant RSV infections, Novavax will need to conduct a clinical trial on more patients than it can afford to enroll. It is difficult to calculate the number of patients required to obtain acceptable confidence intervals, but a 50% effective vaccine to control an infection that 3% of the placebo group intake must recruit at least 10,450 subjects. Severe RSV infections were reported in less than 2.4% of unvaccinated infants during the Prepare study, meaning that a study involving 10,450 subjects would probably not be large enough.

Where does this leave Novavax?

ResVax is likely to provide preventative benefits, but Novavax will never be able to conduct a study of sufficient importance to prove it. After spending $ 135.4 million in the first nine months of 2018, Novavax ended September with only $ 145.6 million in cash and investments.

Investors who hope to have a large pharmaceutical company looking at the results of Prepare and decide to take a high risk by joining Novavax will probably be disappointed. In the Prepare study, approximately 998 tested subjects were enrolled in the United States and were not successful. In fact, severe RSV infections were 32.7% more common among vaccinated Infants in the United States Without a 57% higher efficacy rate among the 2,179 patients enrolled in South Africa, the overall results of the Prepare study would have been unequivocal failure.

Novavax's chances of recovering from this failure are worse than before, but that will probably not prevent the company from trying to collect more money by touting impressive numbers that do not mean much to regulators . While there is nothing wrong with highlighting the interesting side objectives that have been achieved, they are not going to convince the FDA to approve ResVax.

Cory Renauer does not own any of the shares mentioned. The Motley Fool has no position in any of the actions mentioned. Motley Fool has a disclosure policy.