Vaccination immunized seronegative participants
to levels consistent with or above seropositive titers and boosted
baseline titers in seropositive participants
Vaccine was generally well-tolerated
Phase 2 study to confirm dose to be initiated
in near term, with planned interim analysis through 3 months; Phase
3 study planning is underway
CMV is the most common infectious cause of
birth defects in the U.S.; there is no approved vaccine to prevent
CMV
Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology
company pioneering messenger RNA (mRNA) therapeutics and vaccines
to create a new generation of transformative medicines for
patients, today announced positive data from the three-month
interim analysis of safety and immunogenicity of the Phase 1 study
of its investigational cytomegalovirus (CMV) vaccine (mRNA-1647).
mRNA-1647 is a wholly owned program in Moderna’s prophylactic
vaccine portfolio.
Based on these data, Moderna is advancing mRNA-1647 to a
dose-confirmation Phase 2 study in the near term. Preparation has
also begun for a pivotal Phase 3 study designed to evaluate the
efficacy of mRNA-1647 against primary CMV infection. The Phase 2
study will test the intended Phase 3 formulation, which contains
the same proprietary lipid nanoparticle (LNP) used in this Phase 1
study.
mRNA-1647 is a vaccine combining six mRNAs in a single vial,
which encode for two antigens on the surface of CMV: five mRNAs
encoding the subunits that form the membrane-bound pentamer complex
and one mRNA encoding the full-length membrane-bound glycoprotein B
(gB). Both the pentamer and gB are essential for CMV to infect
barrier epithelial surfaces and gain access to the body. mRNA-1647
is designed to produce an immune response against both the pentamer
and gB for the prevention of CMV infection.
“I am very encouraged by the ability of mRNA-1647 to induce high
levels of durable immune responses that can reach or exceed the
levels generated by natural CMV infection,” said Tal Zaks, M.D.,
Ph.D., chief medical officer at Moderna. “We recognize there is an
urgent need for a preventative vaccine against congenital CMV and
will be advancing mRNA-1647 into a Phase 2 study in the near term
to confirm the appropriate dose, while we plan for a pivotal Phase
3 study.”
“Cytomegalovirus is the leading infectious cause of birth
defects, and there is a great need for a vaccine that blocks
transmission of the virus from the mother to the fetus,” said
Sallie Permar, M.D., Ph.D., associate dean of physician scientist
development and professor of pediatrics, immunology, and molecular
genetics and microbiology at Duke Medical School. “These interim
data are exciting because mRNA-1647 has shown the ability to induce
immune responses in seronegative individuals that are greater than
what is seen in those naturally infected with CMV, which is
important in that natural immunity is not completely protective
against congenital CMV transmission.”
The Phase 1 study, which has completed enrollment, is evaluating
the safety and immunogenicity of mRNA-1647 in 169 healthy adult
volunteers. The study population includes those who were naïve to
CMV infection (CMV-seronegative) and those who had previously been
infected by CMV (CMV-seropositive). Participants were randomized to
receive either placebo, or 30, 90, 180 or 300 µg of mRNA-1647 on a
dosing schedule of 0, 2 and 6 months. This first planned interim
analysis assessed safety and immunogenicity of the first three dose
levels (30, 90, and 180 µg) at three months, one month after the
second vaccination and before the third vaccination. Neutralizing
antibody titers (levels of circulating antibodies that block
infection1) were assessed in two assays utilizing epithelial cells
and fibroblasts, which measure immune response to the pentamer and
gB vaccine antigens, respectively. Seropositive baseline titers are
associated with lower rates of congenital CMV transmission.
In seronegative participants:
- A dose-related increase in neutralizing antibody titers was
observed in both epithelial cell and fibroblast assays.
- In epithelial cells, after the second vaccination, neutralizing
antibody titers were 3 to 5 times higher than CMV-seropositive
baseline titers at the 90 and 180 µg dose levels.
- In fibroblasts, after the second vaccination, neutralizing
antibody titers were equivalent to CMV-seropositive baseline titers
at the 90 and 180 µg dose levels.
- For the 12 sentinel participants who received mRNA-1647 under
an earlier arm of the protocol (Phase A) and who received three
doses (at 0, 2 and 6 months), neutralizing antibody titers were
further boosted at 7 months and were sustained at or above
CMV-seropositive baseline levels for at least 12 months.
In seropositive participants:
- A dose-related increase in neutralizing antibody titers was
observed in both epithelial cell and fibroblast assays.
- In epithelial cells, the second vaccination boosted
neutralizing antibody titers to a level of 10-fold to 19-fold
baseline titers in all dose groups.
- In fibroblasts, the second vaccination boosted neutralizing
antibody titers to a level of 2-fold to 4-fold baseline titers in
all dose groups.
A safety analysis indicated that the vaccine was generally
well-tolerated. There were no vaccine-related serious adverse
events (SAEs). The most common solicited local adverse event (AE)
was injection site pain. The most common solicited systemic AEs
were headache, fatigue, myalgia, chills and fever. In general,
solicited systemic AEs occurred more frequently after the second
dose compared to the first, and were more common in the
seropositive cohorts compared to the seronegative cohorts. The most
common Grade 3 solicited AEs in seropositive participants were
myalgia (9-33% of a given dose cohort), chills and fatigue (9-27%
of a given dose cohort) and fever (0-27% of a given dose cohort).
There was a single Grade 4 AE of an isolated lab finding of
elevated partial thromboplastin time (PTT), which was elevated at
baseline (Grade 1) and self-resolved on the next lab test with no
associated clinical findings.
A similar overall safety and tolerability profile was observed
in an earlier arm of the protocol (Phase A), for which data are
available out to 12 months. Additionally, the 300 µg cohort has
completed the second vaccination without study pause; interim
analysis of safety and immunogenicity is pending.
“We are very pleased with these strong interim results and the
immunogenicity demonstrated by our CMV vaccine. The Moderna
research, development and manufacturing teams have been working to
ensure this program can transition in the near term to a
dose-confirmation Phase 2 study, while also preparing for a pivotal
Phase 3 study with the goal of ensuring commercial readiness,” said
Stéphane Bancel, Moderna’s chief executive officer. “Given the
urgent need for CMV prevention around the world, we believe
mRNA-1647 has the potential to be a blockbuster commercial
opportunity for Moderna. This is the sixth positive Phase 1 readout
for a Moderna investigational prophylactic vaccine, and underscores
why I believe our vaccine platform will be an important pillar of
our future growth.”
About mRNA-1647
mRNA-1647 is a two-antigen vaccine designed to protect against
CMV infection. It combines six mRNAs in a proprietary LNP in a
single vial and encodes for two immuno-dominant proteins of CMV.
mRNA-1647 comprises five mRNAs encoding the subunits of the
pentamer complex and one mRNA encoding the glycoprotein B (gB)
target antigen. The pentamer is important for CMV entry into a
variety of cells, including epithelial and endothelial cells, while
gB is important for entry into all susceptible cells including
fibroblasts.2 A vaccine that produces an immune response against
both the pentamer and gB has the potential to prevent CMV entry
into cells and thus prevent congenital infections. Unlike a
protein-based vaccine, mRNA-1647 instructs cells to specifically
make the pentamer and gB antigens with a structure that mimics the
ones presented to the immune system by the virus during a natural
infection.
Preclinical data previously published in Vaccine showed that
vaccination with mRNA-1647 in animal models elicited potent and
durable neutralizing antibody titers.
About the Phase 1 Study
This randomized, observer-blind, placebo-controlled,
dose-ranging study is designed to evaluate the safety and
immunogenicity of mRNA-1647 in healthy adults. The study is
investigating a three-dose vaccination schedule (0, 2 and 6 months)
of mRNA-1647 at four dose levels (30, 90, 180 and 300 μg) in both
CMV-seronegative and CMV-seropositive participants. Primary outcome
measures include solicited AEs. Secondary outcome measures include
anti-CMV neutralizing antibody titers against epithelial cell
infection and fibroblast cell infection.
About mRNA-1647 Development
The first planned interim analysis of the Phase 1 study includes
data from one month after the second vaccination with mRNA-1647 at
30, 90 and 180 µg dose levels. Forthcoming data from the Phase 1
study will include safety and immunogenicity analyses of the 300 µg
dose group as well as data from the third vaccination of all
participants at the 30, 90 and 180 µg dose levels. Full Phase 1
data will be presented at a future medical meeting.
Based on these Phase 1 interim data, Moderna is advancing
mRNA-1647 into a Phase 2 dose-confirming study in the near term,
where the first interim safety and immunogenicity analysis is
planned at 0, 2 and 6 months. This Phase 2 study will test the
intended Phase 3 formulation, which contains the same proprietary
lipid nanoparticle (LNP) used in this Phase 1 study. In parallel,
preparation is underway for the pivotal Phase 3 study designed to
evaluate mRNA-1647 for the prevention of primary CMV infection in a
population that includes women of childbearing age. The design of
this Phase 3 study is subject to FDA and global regulatory
feedback.
About Cytomegalovirus (CMV)
CMV is a common pathogen and member of the herpesvirus family.
Congenital (present at or before birth) CMV infection results when
infected mothers transmit the virus to their unborn child, and it
is the leading infectious cause of birth defects in the United
States with approximately 25,000 newborns in the U.S. infected
every year.3,4 Birth defects occur in approximately 20 percent of
infected babies and include neurodevelopmental disabilities such as
hearing loss, vision impairment, varying degrees of learning
disability and decreased muscle strength and coordination.5 There
is currently no approved vaccine for the prevention of CMV
infection.
CMV is spread through saliva, mucus and urine and is common in
healthy babies and toddlers; as a result, young children can be a
major source of infection for pregnant women, particularly mothers,
daycare workers, preschool teachers, therapists and nurses. Efforts
to create a vaccine began in the 1970s, and in 1999 the Institute
of Medicine (now National Academy of Medicine) designated CMV as a
“highest priority” category for vaccine development. Prior studies
of investigational vaccines that did not protect against the CMV
pentamer antigen demonstrated limited efficacy against CMV
infection and limited durability of immune response.
About Moderna’s Prophylactic Vaccines Modality
Moderna scientists designed the Company’s prophylactic vaccines
modality to prevent or control infectious diseases. This modality
now includes eight development candidates, all of which are
vaccines against viruses. The potential advantages of an mRNA
approach to prophylactic vaccines include the ability to mimic
natural infection to stimulate a more potent immune response,
combining multiple mRNAs into a single vaccine, rapid discovery to
respond to emerging pandemic threats and manufacturing agility
derived from the platform nature of mRNA vaccine design and
production.
Moderna currently has five development candidates for potential
commercial uses in this modality, including: respiratory syncytial
virus (RSV) vaccine (mRNA-1777 and mRNA-1172 or V172 with Merck),
cytomegalovirus (CMV) vaccine (mRNA-1647), human metapneumovirus
and parainfluenza virus type 3 (hMPV+PIV3) vaccine (mRNA-1653) and
Zika vaccine (mRNA-1893) with the Biomedical Advanced Research and
Development Authority (BARDA). Three development candidates in this
modality are being explored for potential global health uses
including: influenza H10N8 vaccine (mRNA-1440), influenza H7N9
vaccine (mRNA-1851) and chikungunya vaccine (mRNA-1388) with the
Defense Advanced Research Projects Agency (DARPA).
To date, Moderna has demonstrated positive Phase 1 data readouts
for six prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus,
hMPV+PIV3 and CMV). Moderna’s investigational Zika vaccine
(mRNA-1893), currently in a Phase 1 study, was recently granted FDA
Fast Track designation.
R&D Day Webcast Today
The Company also announced positive Phase 1 data for mRNA-1944
(mRNA encoding for antibody against chikungunya virus) today. A
summary of data from both of these Phase 1 trials will be presented
at the Company’s annual R&D Day, being held today in New York
City beginning at 8:30 a.m. ET. A live webcast will be available
under “Events & Presentations” in the Investors section of the
Moderna website at https://investors.modernatx.com. A replay of the
webcast will be archived on Moderna’s website for 30 days following
the presentation.
About Moderna
Moderna is advancing messenger RNA (mRNA) science to create a
new class of transformative medicines for patients. mRNA medicines
are designed to direct the body’s cells to produce intracellular,
membrane or secreted proteins that can have a therapeutic or
preventive benefit and have the potential to address a broad
spectrum of diseases. Moderna’s platform builds on continuous
advances in basic and applied mRNA science, delivery technology and
manufacturing, providing the Company the capability to pursue in
parallel a robust pipeline of new development candidates. Moderna
is developing therapeutics and vaccines for infectious diseases,
immuno-oncology, rare diseases and cardiovascular diseases,
independently and with strategic collaborators.
Headquartered in Cambridge, Mass.,
Moderna currently has strategic alliances for development programs
with AstraZeneca, Plc. and Merck, Inc., as well as the Defense
Advanced Research Projects Agency (DARPA), an agency of the U.S.
Department of Defense; the Biomedical Advanced Research and
Development Authority (BARDA), a division of the Office of the
Assistant Secretary for Preparedness and Response (ASPR) within the
U.S. Department of Health and Human Services (HHS). Moderna has
been ranked in the top ten of Science’s list of top biopharma
industry employers for the past four years. To learn more, visit
www.modernatx.com.
Special Note Regarding
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended including, but not limited to, statements
concerning: advancing mRNA-1647 into a dose-confirmation Phase 2
study; preparation for a pivotal Phase 3 study of mRNA-1647 against
primary CMV infection; the potential blockbuster commercial
opportunity for mRNA-1647; the potential for Moderna's vaccine
platform to support its future growth; and mRNA-1647’s potential to
protect against CMV infection and prevent congenital CMV infection.
In some cases, forward-looking statements can be identified by
terminology such as “will,” “may,” “should,” “expects,” “intends,”
“plans,” “aims,” “anticipates,” “believes,” “estimates,”
“predicts,” “potential,” “continue,” or the negative of these terms
or other comparable terminology, although not all forward-looking
statements contain these words. The forward-looking statements in
this press release are neither promises nor guarantees, and you
should not place undue reliance on these forward-looking statements
because they involve known and unknown risks, uncertainties and
other factors, many of which are beyond Moderna’s control and which
could cause actual results to differ materially from those
expressed or implied by these forward-looking statements. These
risks, uncertainties and other factors include, among others:
whether the interim results for mRNA-1647 will be predictive of the
final results for the ongoing study or any future clinical studies;
whether mRNA-1647 will be unsafe or intolerable during further
clinical studies; the fact that clinical development is lengthy and
uncertain, especially for a new class of medicines such as mRNA,
and therefore our clinical programs or development candidates may
be delayed, terminated, or may never advance; no mRNA drug has been
approved in this new potential class of medicines, and may never be
approved; mRNA drug development has substantial clinical
development and regulatory risks due to the novel and unprecedented
nature of this new class of medicines; and those risks and
uncertainties described under the heading “Risk Factors” in
Moderna’s most recent Annual Report on Form 10-K filed with the
U.S. Securities and Exchange Commission (SEC) and in subsequent
filings made by Moderna with the SEC, which are available on the
SEC’s website www.sec.gov. Except as required by law, Moderna
disclaims any intention or responsibility for updating or revising
any forward-looking statements in this press release in the event
of new information, future developments or otherwise. These
forward-looking statements are based on Moderna’s current
expectations and speak only as of the date hereof.
1 Centers for Disease Control and Prevention. 2 McVoy, Michael
A. Cytomegalovirus vaccines. Clinical Infectious Diseases. 2013;
57(Suppl 4): S196-S199. 3 Congenital CMV and Hearing Loss. Centers
for Disease Control and Prevention. Available at:
https://www.cdc.gov/cmv/hearing-loss.html. 4 Schleiss et al.
Progress toward development of a vaccine against congenital
cytomegalovirus infection. Clinical and Vaccine Immunology. 2017;
24(12): e00268-17. 5 Congenital CMV and Birth Defects. American
Pregnancy Association. Available at:
https://americanpregnancy.org/birth-defects/congenital-cmv-birth-defects/.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190912005220/en/
Moderna Contacts:
Media: Colleen Hussey Senior Manager, Corporate
Communications 203-470-5620 Colleen.Hussey@modernatx.com Dan
Budwick 1AB 973-271-6085 dan@1abmedia.com Investors: Lavina
Talukdar Head of Investor Relations 617-209-5834
Lavina.Talukdar@modernatx.com
Moderna (NASDAQ:MRNA)
Historical Stock Chart
From Aug 2024 to Sep 2024
Moderna (NASDAQ:MRNA)
Historical Stock Chart
From Sep 2023 to Sep 2024