The Co-Chair of the Steering Board (European Commission) welcomed participants and
introduced the independent experts.
By way of introduction
Regarding the adenoviral vaccines,
informed that there are
teams
world-wide working on these vaccines.
1 Platforms are technologies used to express the viral antigens.
2
With respect to AZ, and the recent publication of their latest clinical trial results in
The
Lancet medical journal,
acknowledged that the vaccine can induce protection
in rhesus macaques, however the animals continue to secrete the virus via the nasal tract and
hence the vaccine would not effectively block transmission of the disease. The data in
humans show neutralising antibodies of moderate titers, good T-cell immunity as AZ is
relatively advanced
in their Phase III clinical
trial. Whilst the advantage of this platform is the ease with which the vaccine could be
produced, the immunogenicity in older adults is yet to be demonstrated/ observed.
issued the recommendation to continue monitoring this candidate’s evolution
.
With regards to Johnson & Johnson (J&J), a vaccine based on human Adenovirus 26 was
expected to enter Phase I clinical trials on
July in Belgium and in US in people older than
55 years of age. The booster would follow the first administration at day 56.
Immunogenicity evidence was scarce to
date
complemented the analysis of
highlighting that the AZ approach is
relatively good. Since the Phase II clinical trial participants were 18-50 years of age, further
trials should include the 65+ contingent as the latter is more susceptible to contracting the
disease. The recent publication includes some data on prophylactic use of paracetamol. The
most effective schedule appears to be based on two doses, a first administration followed by a
booster.
Emerging data on duration of protection or sterilising immunity is an outstanding
issue.
On the J&J candidate,
stated that the Phase II CT is starting this July, hence no
solid opinion of this vaccine as yet. However, it may well be as promising as the AZ
candidate. In conclusion, both the AZ and the J&J candidates may prove to be good options,
based on currently available information.
3
started by introducing
agreed
AZ product is
more advanced in development but the J&J product is from a company that is well aware of
the adenoviral platform and has a lot of expertise. Whilst both parties draw on their solid
background, 1:1 comparability of their products may well be hindered by the fact that assays
are likely different
. For the AZ candidate, immunogenicity
looked good, although painkillers may be needed for mitigating side-effects.
She mentioned
NOVAVAX having a potentially serious candidate as well in the long run.
thanked for the contributions and moved on to the mRNA platform category
.
explained that the assessments
pertained to
the candidates put forward by Moderna, BioNTech and CureVac,
.
With regards to Moderna’s and BioNTech’s candidates, the mRNA used has a modification
which enhances the odds of inducing an immune response.
. Moderna is starting their Phase III clinical trials. In animal studies, Moderna’s
candidate has shown partial protection against the disease, yet not against infection; in human
studies, it has triggered a relatively high reactogenic reaction
.
A dose of 100 microgram is the highest tolerated by vaccinnees
. The
recruitment is completed for Phase II CT
, with Phase III planned covering
30 000 vaccinees in the US. Moderna decided to cancel their European CT planned
.
highlighted that
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agreed that rather big differences in the data currently available exist with
hardly any results for CureVac, rendering ranking difficult. Moderna recently published a
study in the
New England Journal of Medicine for their mRNA-1273 candidate with similar
results in the older group as in other studied groups. Moderna also shared some confidential
data for which a publication is forthcoming.
Regarding the BioNTech product,
did not completely agree with
counterpart.
On CureVac’s product, the
may well have more information and
theoretically, it could be a good candidate but lagging behind currently. The only official data
seen by
was limited
.
In conclusion, Moderna and BioNTech are promising candidates for
, with good
immunogenicity profile and good tolerability also in the older age group.
.
then proceeded to the Sanofi-Pasteur and NOVAVAX category (the subunit
vaccines).
explained that Sanofi-Pasteur are a large producer and have
vaccines in
their portfolio as well as the expertise of producing vaccines as their core business. In terms
of timing,
acknowledged that they
planning to start their Phase I
CT in
.
The technology is adapted from that developed for one of their seasonal
influenza vaccines (technology acquired from Protein Sciences). The antigen is administered
with a squalene-containing adjuvant
.
In terms of production capacity, purification of antigens from insect cells
infected with a recombinant baculovirus encoding the SARS-CoV-2 S protein (a well-
controlled procedure adapted from that developed for seasonal influenza vaccine). Sanofi-
Pasteur has the necessary infrastructure to ensure very large-scale production.
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With respect to the candidate put forward by NOVAVAX,
informed that
certainly one to be followed very
closely. The antigen is a complete recombinant Spike protein of SARS-CoV-2, stabilised in a
pre-fusion conformation. The antigen is presented as trimers on lipid nanoparticles, normally
more immunogenic than those on lipid form. The candidate is capable of producing high
titers
even at the
lowest dosage tested. Matrix-M™ adjuvant (saponin, cholesterol and phospholipid-based).
Preclinical studies in mice and challenge experiments in non-human primates. Results of an
infectious challenge study in macaque monkeys show a reduction in viral load in the upper
respiratory track and lungs of vaccinated animals, suggesting a protective effect of the
vaccine candidate. It is of note that the dose of virus used for the infectious challenge
corresponds to the dose used by Moderna, but is lower than the dose used by AstraZeneca.
Phase I CT commenced in May in Australia, Phase II ongoing currently in US and Australia.
Production capacity is very high, with recently acquired capacity in CZ. NOVAVAX clearly
capable of producing large amounts of vaccine. Plan to produce
doses in
.
On Sanofi,
issued a note of caution regarding its AS03 adjuvant. GSK used this
adjuvant in their pandemic vaccine and it induced narcolepsy in adolescents in 2009-2010.
Many studies published since then and it seems that narcolepsy was not caused by the
adjuvant itself, but by an antigen (one produced in BE, one in Canada) and only one of these
seems to have caused narcolepsy.
quoted a study published in 2018 in the journal “Vaccine” which did not find
an association between Sanofi’s pandemic flu vaccine and narcolepsy in children and adults.
No data in humans yet from Sanofi’s candidate. As regards NOVAVAX, it seems that the
vaccine can induce an immune response in vaccinees.
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found NOVAVAX’s Matrix-M™ formulation of interest. Perhaps a plus for the
NOVAVAX product is the T-cell response
In
concluding remarks,
highlighted the importance of spreading the vaccine portfolio
over different platforms. The mRNA candidates are
for authorisations,
. Manufacturers in this category draw on
their experience with this platform, known for its effectiveness in respiratory infectious
diseases.
thanked all speakers and opened the Q&A session.
Expert pointed out that direct comparisons of vaccine candidates should be
avoided. Having read all published papers,
wondered whether the limited number of
participants in the BioNTech study data would be an issue and if the multivalent display in
their mRNA design engendered any reactions.
also invited comments on their lipid
envelope.
acknowledged the intrinsic difficulty in drawing comparisons, generally speaking
but a platform by platform comparison is feasible. There were a lot of data in animal studies.
Difficult to have a definitive
conclusion but it seems reasonable to take different elements into account.
Expert enquired about storage temperatures.
explained that Moderna’s candidate consists in a powder to be reconstituted. It
should be stored at -20 to -40° C
. The BioNTech candidate indicated -80°C for long-term storage.
Whilst CureVac’s candidate has two-dose vials stored frozen at -80°C for long-term storage,
stability at 4°C can be preserved for several months. NOVAVAX has ten-dose vials
(reconstituted for use), storage at -80° for several years but also at higher temperatures for
administration. AZ has ten-dose vials, stable at 4°C for 6 months. J&J has ten-dose vials,
stable for several months at 4°C to 10°C.
enquired how these temperatures might impact a vaccine’s workability in
primary care centres in LMI countries.
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responded that for Ebola vaccines in Africa, storage was in liquid nitrogen (in a
cold chain container), keeping the temperature quite well.
(SE) suggested that
a more traditional adjuvanted
protein vaccine would be needed for the elderly.
enquired whether adjuvants could be
avoided at all.
replied that the jury is still out on that aspect.
Similar uncertainties remain for
the other categories.
shared that current plans involve seeking to organise small immunogenic studies for
the very old – over 75 years of age. Some manufacturers want to work with
on this.
wondered whether informing manufacturers of this forum’s endorsement may bring value
added.
suggested that an independent organisation might compare samples from
different CTs.
The Chair (EC) highlighted that
Nobody
knows what the future will hold. The Steering Board, along with the EC, can make informed,
educated guesses and this is what we are seeking to do via the portfolio. A demand we are
making recurrently is Phase III CT data.
We note the suggestion to contact NOVAVAX but
doubts remain over their ability to deliver to the EU
. A
more traditional candidate such as the one put forward by Sanofi (or NOVAVAX), AZ or
J&J is of interest. In the mRNA category, we will need to rely on other elements, not just
scientific ones. Moderna is having a very commercial proposition, BioNTech/ Pfizer
guarantees scalability whilst on CureVac, seemingly a good product but having difficulties to
understand if they can produce at scale. The panel could have been clearer on the mRNA
category.
clarified that
was referring to getting biological samples in this
unprecedented vaccine development race with everyone wanting to be able to make a good
judgment on products.
deemed it fair to ask the companies to collaborate in a
standardised assay to measure the data,
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Expert shared
concerns that the companies may well be apprehensive in this
regard.
.
Expert expressed concerns over the respect of purely scientific criteria in the
ongoing negotiations.
The Chair (EC) explained that the matter is rather more complex in that the Steering Board
decides which companies to open negotiations with. For NOVAVAX, for example, no
contact has been established
continued that the panel is not fully clear in their comparative assessment also
because the information is not equally available.
The Chair (EC) concluded discussions thanking all for their participation
.
also pointed out no objections from the
Steering Board to the AZ candidate; good comments for J&J but a duplication of the AZ
platform. For the innovative mRNA group, any of them would do for different reasons:
scientific reasons for some or other reasons for others. The EC heard the panel’s views on the
scientific data for CureVac’s candidate.
The JNT has not
declined any of the candidates discussed today so this discussion will feed productively into
future ones.
The co-Chair (AT) thanked
(NL) and the Commission for putting this session
together.
closed off the debate
. Much too early to make a decision on turning down a
candidate, although we are closing in on a portfolio.
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Participants
(AT, Co-Chair)
(NL)
(BE)
(BE)
(BG)
(CZ)
(CZ)
(DE)
(DK)
(EE)
(EL)
(ES)
(FI)
(FR)
(FR)
(HU)
(IE)
(IE)
(IT)
(LT)
(LV)
(PL)
(PL)
(PL)
(PT)
(PT)
(PT)
(PT)
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(SE)
(SI)
(SI)
(SK)
Sandra Gallina (EC, Chair)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC, Minutes)
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