NVAX
Bioinvest, están como nosotros, que no saben qué ha podido fallar...
MTSL:
Breaking News (Issued shortly after the 5:00 PM Thursday NVAX call)
BIOINVEST BREAKING NEWS – Special Update – NVAX – Despite Nine Positive Trials With The RSV Vaccine, RESOLVE Is a Failure – In a major, unexpected failure, the highly-anticipated Phase III trial, RESOLVE study, testing NVAX’ heralded RSV F-protein vaccine was unsuccessful. The Phase III trial in 11,856 older adults (60 years of age and older), did not meet the pre-specified primary or the secondary efficacy objectives, and did not demonstrate vaccine efficacy.
Phase 3 Resolve Trial – The trial was a randomized, observer-blinded, placebo-controlled trial conducted at 60 sites in the United States. The primary objective of the Resolve trial was to demonstrate efficacy in the prevention of moderate-severe RSV-associated lower respiratory tract disease (RSV msLRTD), as defined by the presence of multiple lower respiratory tract symptoms. The secondary objective of the trial was to demonstrate efficacy of the RSV F Vaccine in reducing the incidence of all symptomatic respiratory disease due to RSV (RSV ARD). Finally, the trial also evaluated the safety of the unadjuvanted, 135 microgram dose of the RSV F Vaccine compared to placebo.
Summary of Primary and Secondary Objectives – Vaccine Efficacy
Number of Participants - ITT Population (11,856)
Primary and Secondary
Objectives Placebo
(5,935) Vaccine
(5,921) Vaccine
Efficacy (CI) P-Value
Primary: RSV msLRTD, N(%) 26 (0.44%) 28 (0.47%) -7.9 % (-84, 37) 0.78
Secondary: RSV ARD, N(%) 117 (1.97%) 102 (1.72%) 12.6 % (-14, 33) 0.32
What The Blank (F) Happened? With the RSV vaccine and placebo efficacy appearing similar (see table above), after nine successful Phase I and II studies showing strong and consistent immunogenicity (especially compared with MedImmune’s Synagis) one has to scratch their head as to why the study was such a disaster.
Management did their best to suggest some reasons for the outcome (weak season, changes in vaccine itself), but unfortunately both arms performed equally and therefore, the results may not be able to be explained by some unexpected event. Maybe F-protein immunogenicity alone does not necessarily correlate to clinical outcome – despite the favorable comparison to Synagis (and that is what got Synagis approved).
a) Weak RSV Season – The attack rate for the Phase III primary objective was ~25% of that observed in Phase II trial. Historically, annual seasonal RSV ARD attack rates between 3% and 7% have been observed in older adults. In the Phase II trial, the RSV ARD attack rate was 4.9% and an RSV msLRTD attack rate was 1.8%.
In contrast, NVAX observed an RSV ARD attack rate of 2.0% and an msLRTD attack rate of 0.4% in the RESOLVE trial.
These attack rates indicate a mild RSV season in older adults this year, and one of the lowest ever recorded.
That by itself does not change the equivalent results. With the input on trial design from the FDA (as well as Fast Track designation), management believed the bar for RESOLVE was actually lower than that of the Phase II study.
It's so hard to see why or how this trial failed.
b) Phase 2 Rollover Trial – Novavax also reported topline results from the Phase II rollover clinical trial of its RSV F Vaccine in older adults. The trial was a randomized, observer-blinded, placebo-controlled rollover trial that enrolled 1,329 older adults from the prior Phase II trial, conducted at the same 10 sites in the United States.
The rollover trial demonstrated immunogenicity in all active vaccine recipients. The event rate comparisons made to either placebo groups suggested that the second season immunization was protective, even in a year with a very low attack rate.
This is a little more promising and also conflicts somewhat with the Phase III study results. Further understanding of these data may come with full evaluation of the immune responses.
c) Next Steps Hard To Predict – With the preponderance of 9 positive studies and consistently robust immune responses, management believes there is still hope for the RSV vaccine.
They do not believe that their technology does not work.
The did not see any difference with this season’s vaccine than last year (e.g., micronutrients, antibodies, etc.)
There are other vaccines in the pipeline (e.g. flu and pandemic flu, Zika, MERS), and the new nanotechnology of the flu vaccine will start next year. Preclinical data is impressive but its still an early stage program. They will have to consider the combination “respiratory” vaccine studies also based on the RESOLVE study results.
However, the value of this Company was rightfully based on the RSV vaccine. They will update investors at the upcoming October 11 analyst meeting in NYC.
d) $300+ Million In Cash But Debt Too – There are 7 years left on the debt (~$330 million due 2023) and most likely the burn rate will drop.
Conclusion – Tough To Do This, But Must Move To Hold – This negative data is a huge shock to us (and we’re certain to the Company as well). We have followed the journey of this program for more than 3 ½ years. The last few months have included execution and preparation on a Big Pharma/Bio level. The Company has hired leaders in various fields (mfg, regulatory, medical affairs, etc., and the majority of the successful Synagis team).
More info on the potential paths forward for the RSV vaccine and the remainder of the pipeline will be available at the upcoming analyst meeting October 11th.
With little information regarding the potential paths forward for the vaccine candidate it is hard to assign significant value to the program at this point. After the market, the stock is trading at ~$1.40 which is just above the cash levels – suggesting little hope going forward.
However, based on the RESOLVE data (not even a trend), we are moving NVAX to a HOLD until we can decipher the next steps and maybe understand what exactly went wrong. NVAX is now a HOLD."
