. In relation to the second question, CureVac explained that they have just started
a pilot study to test the model itself and also looking into a mouse model that they could use with
a view to obtaining more confidence/ support on efficacy data for Phase III CT data.
commended CureVac on the considerable improvement for the higher dose
regimen and all the immune assays and reactogenicity profiles. Questions were asked on new
data: for reactogenicity, Spike-specific multifunctional CD4+ T-cells were measured, but is
CureVac also measuring the type 2 cytokines for a balanced response and whether they would
expand those data for the 12μg group. A second question on the upfront prescription of
paracetamol was asked in view of addressing more prolonged severe effects after the second
dose in the 12μg reactogenicity group. CureVac concurred with the suggestions of the speaker
for both questions and confirmed that T-cell analysis is underway in the cytokine panel;
expansion to 12μg is ongoing. Based on previous rabies data, no signs of biased Th2 responses
were observed. On the prophylactic use of paracetamol, CureVac explained that whilst
recommended (posology 500 mg), the company do not wish to impose it.
A question was asked on the chosen locations for the roll-out of the Phase III study. CureVac
replied that the latter would take place in
.
Another question was asked about the reactogenicity profile in seropositives as the latter appears
to be lower with a response even after the first dose. CureVac explained that the recent data gives
a lot of hope with respect to the induction of memory cells in patients.
.
A further question was asked regarding the increase in IgG titers. CureVac replied that
for
the
dose, an increase
for all subjects
was observed.
provides further data on NAbs, also for IgG (binding antibodies), for
which a similar increase is observed. The increase is more pronounced for subjects that have low
antibody titers. The reactogenicity also seems to be lower compared to the naïve persons. In the
Phase III trial, proportion of seropositive subjects may well be higher. For IgG, the picture is
very similar.
asked whether testing of 16μg and 20μg in humans was planned. CureVac
explained that these assays are ongoing. Safety of those higher dosages is being monitored.
Whilst there are not many vaccinees in the 16μg and 20μg group (under 20 vaccinees) amounting
to a relatively small sample, the observation that reactogenicity increases with the dose is of
note. Consensus around the 12μg dose exists in view of a balanced human response
reactogenicity.
enquired about regulatory approvals for a Phase III start in
.
CureVac was asked whether they have considered how their plans can be modified just in case
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other vaccines obtain regulatory approval before them and how their Phase III trials could be
adjusted in this light. A question was also asked about the use of more than two doses. CureVac
replied that Phase IIb/ III trials are indeed planned in
CureVac further explained
that it is predictable that other vaccines would be on the market. Some vaccines might obtain
approval whilst CureVac Phase III study is ongoing – in this case CureVac has an obligation to
inform the vaccinees, as these developments might impact their willingness to continue the
study. Subjects eligible to participate might indeed leave the study as information from
competitors comes in, hence adjustments in the study planning may well be needed. With respect
to the prospect of having three doses, CureVac informed that
The company further explained that the
A question on publication timelines was raised. CureVac informed that in the coming week the
work would be presented at an mRNA Conference and a publication would be prepared in
parallel. Regarding the NHP data, the partnership with PHE for the manuscript is expected to
result in a publication in
.
requested the final version of the presented slides and referred to the
reactogenicity in the older group and whether expectations for immunogenicity and
reactogenicity in this group would not be for lower read-outs. CureVac replied that the point was
well taken and in view of the few subjects
, more data would be needed for an
assessment. CureVac also clarified that these were a subset of adults and not 60+ adults. As the
studies are in Europe and Latin America, the perception of side effects can be different from
country to country. Whilst fever is objectively measured, all other symptoms (myalgia, fatigue,
etc) are subjective and can change with age and country.
The Chair thanked once again the representatives of CureVac and the company signed off,
allowing for more discussion amongst the experts.
3
expressed a minor reservation regarding reactogenicity which
might jeopardise the acceptance of the second dose. He added that the role of prophylactic
paracetamol was also not very clear. The key aspect compared to other mRNA vaccines is the
storage conservation, i.e. the stability of the CureVac candidate vaccine.
remarked that the company was making good progress on many aspects that
were previously not clear
. Overall, the
development is positive for CureVac and data on paracetamol can still be used in relation to
reactogenicity. The profile chosen by their Data monitoring board is appropriate.
explained that reactogenicity in the case of mRNA vaccines is to be
expected. Low fever is a characteristic of these types of vaccines, with a recent paper by
BioNTech/ Pfizer pointing to high to moderate fever and chills. This is a question of risk/
benefit. AstraZeneca also used Paracetamol, hence not uncommon.
In reply to a question from the Chair,
explained
.
The Chair remarked that the situation may improve with the second wave of vaccines.
agreed that % efficacy is needed for vaccines to render them appropriate for
deployment.
enquired about views on a possible third dose and reactogenicity. As data on 16
and 20μg is still being collected (for the elderly the 12μg dosage may not be enough), a third
dose may be of interest.
confirmed that logistics can be very complicated with three doses.
.
4
expanded that in nursing homes this can be done. In Latin America, a dose
reduction is being tested for improved immunity. If there is a marked improvement, this is
doable – however, if the improvement is marginal, then such a reduction and dosage may not be
worth the effort.
The Chair thanked all experts for their independent views and expertise and concluded that
logistics will likely be key in the choice of vaccines by Member States. The Chair thanked all for
their active engagement and closed the meeting.
Participants
CureVac:
Managing
Technology Officer
Infectious Diseases
COVID-19 Programme Lead
Area Head Infectious Diseases
Supervisory Board
Member States:
(AT)
(DE)
(DE)
(ES)
(ES)
(FR)
(FR)
(FR)
(IT)
(IT)
(NL)
(NL)
5
(PL)
(SE)
European Commission:
Sandra Gallina (EC, Chair)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC)
(EC, Minutes)
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