Replies to post #245600 on Biotech Values

[dewophile]

I have to think the panel will endorse approval of both vaccines. There may be some debate about the 60-65 year olds. The Pfizer data was also “only” 62 percent effective in those with co morbidity.
I expect the more consequential meeting will be ACIP (there will also be more updated data for that meeting)

[dewophile]

Briefing docs are out:
https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-february-28-march-1-2023-meeting#event-materials

Most of the data has already been disseminated, but some info that is new:

1 PFE docs showed efficacy vs LRTI in RSV A of 88.9% (1 vs 9 in vax and pbo ), whereas efficacy vs LRTI in RSV B cases was 56% (10 vs 23 cases in each arm). This did not hold for severe disease or ARI and I don't think it matters for regulatory purposes but just an interesting tidbit, especially since PFE was touting that their vaccine was the only bivalent vaccine derived from both RSV A and B strains yet they are the ones w the numeric disparity
2. PFE efficacy in patients with 1 or more cardiopulmonary comorbidity (i.e. the comorbidity predisposing to the most severe disease) was only 33% (4 vs 6 cases). This one really may matter, especially at ACIP. GSK had 92% efficacy in this subgroup.
3. The 2 cases of GBS in the PFE study prompted this from the FDA:

The applicant did not include any important identified or important potential risks in its
pharmacovigilance plan (PVP). The applicant reported cases of GBS (n=1) and a GBS variant,
Miller Fisher syndrome (MFS) (n=1), in RSVpreF-exposed participants in its pivotal Phase 3
study (Study 1013). Given the uncertain relationship between RSVpreF and GBS (including
MFS) and other immune-mediated demyelinating conditions, FDA is recommending that the
Applicant:
1. Add GBS and other immune-mediated demyelinating conditions to its PVP as an important
potential risk;
2. Submit a proposal for a postmarketing safety study to assess the risk of GBS and other
immune-mediated demyelinating conditions among individuals vaccinated with RSVpreF;

GSK had one case and of couse this will be part of their drug safety monitoring plan if approved as well, but there was no "slap on the wrist" for GBS in their briefing docs
4. GSK's vaccine had an imbalance in cases of Afib. I don't think anyone has any mechanistic explanation, and well there is a lot of afib in old folks, and GSK will argue it is a fluke (I doubt the FDA argues otherwise frankly but it is still something to keep an eye on):

There were no meaningful imbalances in the overall rates of SAEs within 1 month following vaccination between vaccine and placebo recipients in the Safety Population, however a numerical imbalance was noted in events of atrial fibrillation with seven events (0.1%) in the
RSVpreF3-AS01E group and one event (<0.1%) in the placebo group.

5. Both studies were underpowered for severe cases requiring supportive therapy - oxygen, ventilation, etc. along w hospital admission. It's still nice to at least see that numerically the numbers favored the vaccine arms, with 2 cases in each of the studies and all 4 in the placebo arms
6. Deaths were balanced between arms in both studies, but GSK had numerically fewer deaths in the vaccine arm (43 vs 56 at 6 months), while PFE had 3 more deaths in the vaccine arm (52 vs 49). This is statistically meaningless of course, but I thought worth noting
7. GSK had to pause their maternal (unadjuvenated) vaccine due to an imbalance in preterm births. 6.8% vs 4.95% vaccine to placebo (RR 1.38 CI 1.08-1.75). This was primarily in low and middle income countries. No implications for the adult vaccine, but it could add some scrutiny to PFE's maternal vaccine, although it seems to have not suffered from this imbalance
8. GSK has data that the severity of ARI was worse among those that got sick in the placebo arm which has real world implications QOL etc. FDA didn't bother w any of that in their docs. For PFE duration of symptoms was the same for LRTI in each arm, but a bit shorter for severe LRTI in the vaccine arm

In the end I think both vaccines get thumbs up, but the GBS may be a source for some unpleasant headlines.