Valneva Reports Excellent Final
Phase 1 Results for its Chikungunya Vaccine Candidate, Confirms
Plans
Final Phase 1 results up to
Month 13 confirm the excellent immunogenicity and
safety profile for VLA1553, its single-shot
vaccine candidate.
- Company plans to accelerate program to pivotal
Phase 3 trial in 2020 (subject to FDA
agreement) Supportive studies on track to support
End of Phase 2
- Excellent and sustained immunogenicity profile
in all dose groups 100% seroconversion
achieved at Day 14 after a single vaccination
Sustained at 100 % after 12 months with no decline in
neutralizing antibody titers in the groups after a single
vaccination
- Generally safe in all dose groups
Well-tolerated with superior safety profile in low and
medium dose groups compared to high dose group with excellent local
tolerability
Saint Herblain (France),
November 18, 2019 – Valneva SE (“Valneva” or “the
Company”), a biotech company developing and commercializing
vaccines for infectious diseases with major unmet medical needs,
today announced excellent final Phase 1 results for its single-shot
chikungunya vaccine candidate, VLA1553.
The objectives of the Phase 1 study
(VLA1553-101) were to assess the safety and immunogenicity profile
of VLA1553 after a single vaccination across three dose levels.
Today´s final analysis of the study includes the safety and
immunogenicity results up to Month 13 and full results from the
“intrinsic human viral challenge.”
The safety profile observed in the prior
analysis, announced in May 20191, was confirmed. VLA1553 was
generally safe in all dose groups. The low and medium dose groups
were well tolerated and showed a superior safety profile, including
viremia, compared to the high dose group. No adverse events of
special interest (e.g. chikungunya infection related) and no
vaccine related Serious Adverse Events (SAEs) were reported up to
Month 13. The product candidate´s local tolerability profile was
excellent.
The final results showed an excellent
immunogenicity profile in all vaccinated dose groups after a single
vaccination, with a 100% seroconversion2 achieved at Day 14 after a
single vaccination in all dose groups and titers were sustained at
100% at Month 12.
The study was designed so that all study
participants would be re-vaccinated either after 6 months (n=26) or
after 12 months (n=68). There was no anamnestic response observed
after re-vaccination (either after 6 or 12 months) demonstrating
that a single vaccination of VLA1553 is sufficient to induce a
sustained high titer of neutralizing antibodies. All subjects
receiving a second shot (at Month 6 or Month 12) of the vaccine
were protected from vaccine-induced viremia and associated clinical
symptoms, serving as “intrinsic human viral challenge” providing
first indications of efficacy.
While the study finalization was
ongoing, Valneva successfully progressed a number of supportive
studies including mosquito transmission, biodistribution and
persistence in non-human primates (NHPs) as well as a passive
transfer study in NHPs to develop a Correlate Of Protection (COP)
using human sera from VLA1553-101. Valneva expects that the data
provided from these studies will support the Company’s submission
for an end-of-Phase 2 meeting.
Wolfgang Bender, M.D., Ph.D.,
Chief Medical Officer of Valneva commented, “These
fantastic results confirm that VLA1553 is a highly differentiated
and promising vaccine candidate that has the potential to address a
serious threat to public health. On the basis of all our data, we
aim to work with the regulators towards an accelerated approval
pathway potentially allowing us to enter directly into pivotal
Phase 3 next year.”
About The Phase 1 Clinical Study
VLA1553-101This study was a randomized,
observer-blinded, multicenter, dose-escalation Phase 1 clinical
study investigating three dose levels of VLA1553 after a single
immunization. It enrolled 120 healthy volunteers, 18 to 45 years of
age, in the United States. Subjects were randomized into three
different study groups to receive one of three dose levels (30
subjects in the low and medium and 60 subjects in the high dose
group). The protocol includes a re-vaccination with the
live-attenuated vaccine candidate VLA1553 at Month 6 (for 30
subjects in the high dose group) or Month 12 (for all others) to
confirm that a single vaccination will be sufficient to induce high
titer neutralizing antibodies and protect subjects from
vaccine-induced viremia (intrinsic viral challenge). Study
participants were followed up until 13 months after initial
vaccination. An independent Drug Safety Monitoring Board (DSMB)
continuously oversaw the study and reviewed safety data. Additional
information, including a detailed description of the study design,
eligibility criteria and investigator sites, is available at
ClinicalTrials.gov (NCT03382964).
About
Chikungunya Chikungunya is a
mosquito-borne viral disease caused by the chikungunya virus
(CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes.
Clinical symptoms include acute onset of fever, debilitating joint
and muscle pain, headache, nausea and rash, potentially developing
into long-term, serious health impairments. Chikungunya virus
causes clinical illness in 72-92% of infected humans around 4 to 7
days after an infected mosquito bite. Complications resulting from
the disease include visual, neurological, heart and
gastrointestinal manifestations; fatalities have been reported
(case fatality rates of 0.1% to 4.9% from epidemics)3 in elderly
patients at higher risk. Chikungunya outbreaks have been reported
in Asia, Africa, the Americas and recently (2017) in Europe. As of
2017, there have been more than one million reported cases in the
Americas4 and the economic impact is considered to be
significant (e.g. Colombia outbreak 2014: $73.6m5). The medical and
economic burden is expected to grow as the CHIKV primary mosquito
vectors continue to further spread geographically. There are no
preventive vaccines or effective treatments available and, as such,
chikungunya is considered to be a major public health
threat.
About
VLA1553VLA1553 is a monovalent, single
dose, live-attenuated vaccine candidate for protection against
chikungunya and was granted Fast Track designation by the U.S. Food
and Drug Administration (FDA) in December 20186.
In July 2019, CEPI awarded up to US$23.4 million to Valneva
for the programs late-stage development7. The investment comes from
the EU’s Horizon 2020 research and innovation programme under grant
agreement No. 857934.The vaccine candidate is
designed for prophylactic, active, single-dose immunization against
chikungunya in humans over one year old. The vaccine targets
long-lasting protection and an anticipated safety profile similar
to licensed vaccines for active immunization in adults and
children. The target population segments are travelers, military
personnel and individuals at risk living in endemic regions. The
global market for vaccines against chikungunya is estimated at up
to €500 million annually8.VLA1553 is based on an
infectious clone (CHIKV LR2006-OPY1) attenuated by deleting a major
part of the gene encoding the non-structural replicase complex
protein nsP3, aiming for protection against various chikungunya
virus outbreak phylogroups and strains9. In
pre-clinical development, a single-vaccine shot was shown to be
highly immunogenic in vaccinated Non-Human Primates (NHP)
(cynomolgus macaques) and showed no signs of viremia after
challenge10. In NHPs, VLA1553 induced a strong, long lasting (more
than 300 days) neutralizing antibody response comparable to
wild-type CHIKV infections, combined with a good safety
profile.
About Valneva
SEValneva is a biotech company developing
and commercializing vaccines for infectious diseases with major
unmet needs. Valneva’s portfolio includes two commercial vaccines
for travelers: IXIARO®/JESPECT® indicated for the prevention of
Japanese encephalitis and DUKORAL® indicated for the prevention of
cholera and, in some countries, prevention of diarrhea caused by
ETEC. The Company has various vaccines in development including a
unique vaccine against Lyme disease. Valneva has operations in
Austria, Sweden, the United Kingdom, France, Canada and the US with
approximately 490 employees. More information is available at
www.valneva.com.
Valneva
Investor and Media ContactsLaetitia
Bachelot-FontaineGlobal Head of Investor Relations & Corporate
CommunicationsM +33 (0)6 4516 7099investors@valneva.com |
Teresa
PinzolitsCorporate Communications SpecialistT +43 (0)1 20620
1116communications@valneva.com |
Forward-Looking Statements
This press release contains certain
forward-looking statements relating to the business of Valneva,
including with respect to the progress, timing and completion of
research, development and clinical trials for product candidates,
the ability to manufacture, market, commercialize and achieve
market acceptance for product candidates, the ability to protect
intellectual property and operate the business without infringing
on the intellectual property rights of others, estimates for future
performance and estimates regarding anticipated operating losses,
future revenues, capital requirements and needs for additional
financing. In addition, even if the actual results or development
of Valneva are consistent with the forward-looking statements
contained in this press release, those results or developments of
Valneva may not be indicative of their in the future. In some
cases, you can identify forward-looking statements by words such as
"could," "should," "may," "expects," "anticipates," "believes,"
"intends," "estimates," "aims," "targets," or similar words. These
forward-looking statements are based largely on the current
expectations of Valneva as of the date of this press release and
are subject to a number of known and unknown risks and
uncertainties and other factors that may cause actual results,
performance or achievements to be materially different from any
future results, performance or achievement expressed or implied by
these forward-looking statements. In particular, the expectations
of Valneva could be affected by, among other things, uncertainties
involved in the development and manufacture of vaccines, unexpected
clinical trial results, unexpected regulatory actions or delays,
competition in general, currency fluctuations, the impact of the
global and European credit crisis, and the ability to obtain or
maintain patent or other proprietary intellectual property
protection. In light of these risks and uncertainties, there can be
no assurance that the forward-looking statements made during this
presentation will in fact be realized. Valneva is providing the
information in these materials as of this press release, and
disclaim any intention or obligation to publicly update or revise
any forward-looking statements, whether as a result of new
information, future events, or otherwise.
1Valneva PR: Valneva Reports Further Positive Results
for Its Chikungunya Vaccine
Candidate 2Seroconversion is defined as the
proportion of subjects achieving a CHIKV-specific neutralizing
antibody titer of NT50 ≥20.
3 WHO, PAHO4 PAHO/WHO data: Number of
reported cases of Chikungunya Fever in the Americas – EW 51
(December 22, 2017)5 Cardona-Ospina et al. 2015,
Trans R Soc Trip Med Hyg 109:793-802.6
Valneva PR: Valneva Awarded FDA Fast Track Designation for
Chikungunya vaccine candidate7 Valneva PR: CEPI
awards up to US$23.4 million to Valneva for late-stage development
of a single-dose chikungunya vaccin8 Company
estimate supported by an independent market study9
Hallengärd et al. 2013, J. Virology
88:2858-2866.10 Roques et al. 2017, JCI Insight 2
(6): e83527.
- 2019_11_18_VLA_Chikungunya_Final_Phase1_Results_PR_EN