Specialist
Senior Executive at CCC19 (COVID-19 and Cancer Consortium)
Agenda
- COVID-19 clinical trials data, efficacy and safety comparison – Pfizer (NYSE: PFE) vs Moderna (NASDAQ: MRNA) vs AstraZeneca (LON: AZN)
- Preservation and distribution differentiation across Pfizer, Moderna and AstraZeneca's vaccines
- FDA (Food and Drug Administration) regulatory approval for Pfizer, Moderna and AstraZeneca's COVID-19 vaccines
- Target populations and vaccine timelines
- 2020 pipeline and commercialisation outlook for 2021 and beyond
Questions
1.
Could you give an overview of the vaccine regulatory approval process and how exceptional it has been with the COVID-19 candidates? What concerns or issues might result from the expedited process? How could those issues trickle down to distribution?
2.
What read-throughs can be drawn from the EUA [Emergency Use Authorization] granted to Pfizer’s vaccine, especially for the prospective approval of Moderna’s vaccine? What are your expectations for the US government roll-out and coordination of the Pfizer and Moderna vaccines, including the distribution points?
3.
How would you disaggregate the efficacy information across patient populations for the Pfizer, Moderna and AstraZeneca vaccines? The Moderna vaccine didn’t demonstrate great efficacy in the elderly, so how could that bode for Moderna vs the other candidates?
4.
Could you elaborate on how we should approach the follow-on studies to understand patient stratification, given the significant impact this information would have on how vaccine roll-out is prioritised?
5.
Why do you think there was a discrepancy in the data between the half-dose and full-dose protocols for the Oxford-AstraZeneca vaccine? How could the FDA’s [Food and Drug Administration’s] evaluation of the half dose protocol extend the timeline for approval?
6.
Could you compare the immunological or scientific risks of the Oxford-AstraZeneca candidate to those of the first mRNA candidates?
7.
Could the differences in assay designs across the candidates – such as Moderna’s assay not incorporating the killer T-cell responses – impede our ability to draw direct comparisons? How do you think about the significance being placed on neutralising antibodies vs T-cell responses in the assay designs for these candidates? How has the data fared across the platforms?
8.
What do you think would be the most effective way to compare the vaccine data read-outs, given the difficulties you’ve highlighted around making these comparisons?
9.
What are your thoughts on Pfizer tweaking the lipid nanoparticle formulation to allow its vaccine to be transported and distributed without ultra-cold storage, given the company’s commentary around this? What read-throughs should we draw from Pfizer having already invested heavily into freezer farms? On what timeline do you think the company could execute a switch if it succeeds in creating a reformulation that brings its candidate’s storage temperatures closer to Moderna’s?
10.
The US government has taken a significantly different approach to distribution with Operation Warp Speed in comparison to Pfizer, which has taken a lot of the manufacturing and distribution in-house. How do you assess the government’s rhetoric around distribution, especially as there seems to be only 2-3 points of dispatch for Pfizer? Do you think the government is planning for a more conventional roll-out? Do you expect mass distribution to be based on the pipeline of candidates that have more reasonable storage requirements?
11.
What are your expectations for the coordination of centralised vs dispersed dispatch points in hotspot areas and rural vs urban zones?
12.
You mentioned that the long-term storage and maintenance requirements for Moderna and Pfizer’s candidates are fairly similar. Why do you think such stark comparisons are being drawn between them, if this is so?
13.
When do you think the second-generation vaccines will come online? Do you expect initial uptake for the first-generation platforms to plateau, with further volumes being entirely picked up by Johnson & Johnson or Merck’s offerings? These platforms are perhaps more known than the mRNA vaccines.
14.
You suggested earlier that it might be feasible to treat the COVID-19 vaccines as a class rather than differentiating by platform, given the candidates all focus on the spike protein as their core antigen. Could you comment on any differences in the quantity of antigen being factored into the platforms and how this might shape response rates across them, understanding that the positive responses are giving way around the targeting of the specific spike protein on the cell?
15.
How much of the difference in response rates between the mRNA vaccines and the adenoviral vector used by AstraZeneca-Oxford do you think can be attributed to the variation in the antigen and the antigen construct between the platforms? Are there any read-throughs we can derive from the antigen construct in the Oxford AstraZeneca and Johnson & Johnson vaccines?
16.
How would you rank the mRNA vaccines vs the adenoviral vectors vs the subunit adjuvants, understanding that it’s speculative at this point?
17.
Do you think the protein vaccines are more compelling because they might be more efficacious? Do you think they’re just easier to manufacture, meaning they’re more useful for mass-scale administration?
18.
The Novavax candidate has received mixed feedback. Some specialists have said that there might be a great CD-cell response, while others have been more critical. What are your thoughts on Novavax’s CD8 response, which appears to be smaller or suboptimal?
