that the antigen and the adjuvant are both in ten-dose vials. One would need to draw up the
adjuvant from the vial, inject it into the vial of antigen and draw out the formulation for 10
subjects – i.e. 0.5ml per vaccinee/ vaccination.
enquired why Sanofi chose the AS03 adjuvant instead of AS04. Sanofi answered
that they used AS03 in the pandemic influenza vaccine and
AS03 was the most beneficial to protect against infection and against severity of disease based
on their latest assessment.
enquired about the pre-existing prevalence of HLA-DQB haplotypes in the
choice of Sanofi’s trial sites. The narcolepsy post-Pandemrix strongly associated with genetic
predisposition may raise the question of the safety of the product in trial sites with high
prevalence of such genes. Sanofi replied that
have
been addressing the safety of AS03 in response to the narcolepsy observation in the pandemic
influenza vaccine produced by GSK in 2009. Sanofi pointed to the safety of the adjuvant
formulation and that the bulk of the narcolepsy incidence related to genetic predisposition and
the specific sequence of the pandemic influenza vaccine candidate. Safety protocols looking at
sentinel cohorts are one way of investigating the safety profile of the adjuvant.
enquired about the design of the immunogenicity studies and specifically their
duration.
further remarked that convalescents’ sera (studies) are not standardised and within
a few months, subjects previously diagnosed with COVID-19 were re-infected. Sanofi agreed,
convalescent sera studies are not standardised. They used
subjects for the broad panel – some
mild, some moderate and some severe diseased. In terms of the protocol for the trial, the primary
endpoint is modulation of disease severity. Sanofi will be looking at severe disease profiles of
convalescent sera. The second endpoint is protection against disease acquisition. It is therefore
important to look at asymptomatic, infected subjects and whether they would be able to block
acquisition and transmission. The six month durability of the immune response is as important as
efficacy. There is still considerable uncertainty as regards how durable the response is – Sanofi is
still learning what the durable response is and what is the patient durability to natural exposure.
asked about EMA submission timelines. Sanofi replied that meetings in view of
obtaining and following up scientific advice have already taken place. The rolling submission is
and the last package of the rolling submission is planned in
when the last key tables from Phase III studies are expected.
enquired whether adjuvant MF59 was envisaged at all. Sanofi replied that
site selection played a key role. For their Phase I/II studies, Sanofi intends to enrol 18-55 year-
olds and then 55 and older adults.
Furthermore,
unlike MF59, AS03 has already been administered to tens of millions of human subjects already.
.
2
asked about plans to enrol patients with comorbidities (preferably a significant
contingent) for the Phase III trials. Sanofi confirmed that for Phase III, 30.000 patients including
seropositives and seronegatives are included, the primary endpoint being seronegatives. Elderly
and patients with comorbidities are included in Phase III.
enquired about storage conditions. Sanofi answered that short-term storage is
possible at room temperature up to a week. Whilst there is some confirmed stability at 2-8°
Celsius, further stability testing is underway and not confirmed yet.
had a question about the location of the production facilities.
asked how many animals were used per group in NHP studies and whether
challenge studies were performed. Sanofi replied that three different species were used, i.e. six
animals per group in NHP, in cooperation with the VRC (Vaccine Research Centre) and a second
study completed by Sanofi-Pasteur also used six NHP per group.
enquired what age groups would be enrolled in Phase III clinical trials. Sanofi replied
that Phase III CTs are mainly targeted at adults, with the paediatric part having a tailored plan.
The priority is to focus first on high-risk patients and adults with comorbidities, in a balanced
cohort group of adults aged 18 and older, with no age limit. Staging is also key.
remarked that the platform resembles the Flublok® one and enquired whether
any potential interactions between the COVID-19 vaccine and the Flublok® vaccine were
expected. Sanofi replied that in view of immunological interference, the vaccines should be
administered a minimum of two weeks apart.
enquired whether any data was expected on the onset of immunity. Sanofi
replied that GMT titers were demonstrated post-administration after the first dose, with
neutralisation titers picking up after the second dose. The data is strongly supporting a two-dose
regimen administration, although certain levels of antibodies are elicited already after the first
administration.
asked about plans to study the compatibility of this vaccine candidate with
common adult vaccines. Sanofi welcomed the question and replied that more time is needed to
get a proper handle on the pandemic.
3
was interested in exploring what the VE% and the lower end of 95% CI
Sanofi is planning to consider for the primary endpoint in Phase III. Sanofi replied that they are
seeking to harmonise on endpoints and therefore consulting with other manufacturers on their
endpoints.
enquired whether animal challenge studies were done after vaccination
and if so, whether there were any results in protection against infection versus disease. Sanofi
replied that efficacy data on three studies
was expected at
.
The Chair thanked Sanofi for the presentation and the participating experts for the good
discussion and closed the meeting.
Participants
Sanofi-GSK:
Public Affairs for Vaccines Europe, Sanofi Pasteur
External Research And
Development, Sanofi Pasteur
Human Resources, Sanofi Pasteur
Medical Health, Sanofi Pasteur
Regulatory affairs, Sanofi Pasteur
Member States:
(AT)
(AT)
(AT)
(BE)
(BE)
(CZ)
(DE)
(DK)
(DK)
(DK)
(DK)
4
(EE)
(EL)
(ES)
(ES)
(FI)
(FI)
(FR)
(FR)
(HR)
(HU)
(IC)
(IE)
(IE)
(IE)
(IT)
(LT)
(LV)
(LV)
(LU)
(NL)
(NL)
(NL)
(NO)
(NO)
(PL)
(PT)
(RO)
(SI)
(SI)
5
(SK)
(SK)
European Commission:
(EC, Chair)
(EC)
(EC)
(EC)
(EC)
(EC, Minutes)
6