New interim analysis after third and final
vaccination shows continued boosting of neutralizing antibody
titers in both seronegative participants (exceeding seropositive
baseline levels 10-fold at 90 and 180 µg) and seropositive
participants (exceeding baseline levels by 20- to 40-fold at 90 and
180 µg)
Phase 2 interim data at three months, expected
in 2H 2020, intended to inform Phase 3 dose selection
Pivotal Phase 3 study manufacturing and
planning already underway; study start expected in 2021
CMV is the most common infectious cause of
birth defects in the U.S.; there is no approved vaccine to prevent
CMV
Conference call to be held at 8:00 a.m. ET on
Friday, January 10, 2020
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 seven-month interim safety and
immunogenicity data after the third and final vaccination in the
Phase 1 study of its investigational cytomegalovirus (CMV) vaccine
(mRNA-1647). The findings build on the previously reported
three-month interim analysis, after two vaccinations, announced at
the Company’s R&D Day in September 2019. Additionally, the
Company announced that the first participant was dosed in the Phase
2 dose-confirmation study. mRNA-1647 is a wholly owned program in
Moderna’s prophylactic vaccines portfolio.
“Prevention of CMV in women of childbearing age is an urgent
unmet need, which we believe positions our wholly owned mRNA-1647
program as a potential blockbuster commercial opportunity.
mRNA-1647 is the first mRNA vaccine for an infectious disease to
enter a Phase 2 clinical trial,” said Stéphane Bancel, Moderna’s
chief executive officer. “These new data, after the third
vaccination, represent another critical clinical milestone in our
CMV vaccine program and we are extremely pleased with this
continued progress as we move into late-stage development, prepare
for a pivotal Phase 3 study as quickly as possible and ensure
commercial readiness.”
mRNA-1647 comprises six mRNAs encoding two antigens in one
vaccine, and is designed to protect against CMV infection. Of the
six mRNAs, five encode the subunits of the CMV pentamer complex and
one mRNA encodes the glycoprotein B (gB) protein, both of which are
highly immunogenic. Both pentamer and gB proteins are essential for
CMV to enter epithelial cells, which is the first step in CMV
infection. mRNA-1647 is designed to produce an immune response to
both pentamer and gB antigens to prevent CMV infection.
The second interim analysis of the Phase 1 trial reports safety
and immunogenicity of the first three dose levels (30, 90 and 180
µg) through seven months (one month after the third vaccination)
and the highest dose level (300 µg) through three months (one month
after the second vaccination). Neutralizing antibody titers were
assessed in two assays utilizing epithelial cells and fibroblasts,
which measure immune response to pentamer and gB antigens,
respectively.
Safety data were consistent with those reported at the
three-month interim analysis. The vaccine was generally
well-tolerated and there were no vaccine-related serious adverse
events (SAEs). The most common solicited local adverse reaction
(AR) across all vaccinations was injection site pain (54-100% of a
given treatment group). The most common solicited systemic ARs
reported overall were headache, fatigue, myalgia and chills. Fever
was reported in 0-55% of CMV-seronegative treatment groups and in
8-67% of CMV-seropositive treatment groups. The most common Grade 3
solicited ARs were in CMV-seropositive participants, and were
fatigue (0-27% of a given treatment group), chills (0-27% of a
given treatment group) and fever (0-33% of a given treatment
group). In general, the highest solicited systemic AR rates were
reported after the second vaccination, were more frequent in the
CMV-seropositive compared to the CMV-seronegative group, and tended
to correlate to dose. As reported in the previous interim analysis,
one related Grade 4 adverse event (AE) has been observed, which was
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.
In the CMV-seronegative group at seven months:
- Neutralizing antibody titers continued to increase after the
third vaccination in both epithelial cell and fibroblast
assays.
- Neutralizing antibody titers against epithelial cell infection
were greater than 10-fold higher than CMV-seropositive baseline
titers at the 90 and 180 µg dose levels after the third
vaccination, compared to 3-fold to 5-fold higher after the second
vaccination.
- Neutralizing antibody titers against fibroblast infection
increased to 1.4-fold higher than CMV-seropositive baseline titers
at the 90 and 180 µg dose levels after the third vaccination,
compared to titers that were comparable to CMV-seropositive
baseline titers after the second vaccination.
In the CMV-seropositive group at seven months:
- Neutralizing antibody titers continued to increase after the
third vaccination in both epithelial cell and fibroblast
assays.
- Third vaccination boosted neutralizing antibody titers against
epithelial cell infection to levels of 22-fold to 40-fold over
baseline across treatment groups, compared to 10-fold to 19-fold
over baseline after the second vaccination.
- Third vaccination boosted neutralizing antibody titers against
fibroblast infection to levels of 4-fold to 6-fold over baseline
across treatment groups, compared to 2-fold to 4-fold over baseline
after the second vaccination.
Samples from a subset of CMV-seronegative participants from the
30, 90 and 180 µg dose levels demonstrated T-cell reactivity
against the gB antigen at all doses. Pentamer-based T-cell assays
remain in development.
This interim analysis also reports the first data from the 300
µg dose level through three months (one month after the second
vaccination), which continued to show consistent dose-dependent
increases in neutralizing antibodies against epithelial cell
infection and against fibroblast infection in both CMV-seronegative
and CMV-seropositive participants. Safety and tolerability at the
300 µg dose level was comparable to that observed at the 180 µg
dose level.
“These data are significant because they show that after a third
dose, mRNA-1647 continues to increase durable immune responses that
exceed the levels of those with natural CMV infection,” said Tal
Zaks, M.D., Ph.D., chief medical officer at Moderna. “There is no
approved vaccine to prevent CMV infection despite repeated attempts
over the last 50 years. With mRNA-1647, which encodes for both the
pentamer and gB antigens, we believe we can significantly reduce
the burden of CMV infection, including in women of childbearing
age.”
The findings from this interim analysis build on the previously
reported interim analysis of safety and immunogenicity through one
month after the second vaccination in the three lower dose levels
announced at the Company’s R&D Day in September 2019. A
12-month interim analysis is planned, which will report safety and
immunogenicity through six months after the third vaccination.
First Participant Dosed in Phase 2 Study
The first participant has been dosed in the randomized,
observer-blind, placebo-controlled, dose-confirmation Phase 2
study, which will investigate the safety and immunogenicity of
mRNA-1647 in approximately 252 healthy adults in the U.S. at three
dose levels (50, 100 and 150 μg) in both CMV-seronegative and
CMV-seropositive participants administered in a three-dose
vaccination schedule (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 the Phase 1 study. The
first interim analysis will evaluate safety and immunogenicity at
three months (one month after the second vaccination) and is
intended to inform Phase 3 dose selection. mRNA-1647 is the first
mRNA vaccine for an infectious disease to enter a Phase 2 clinical
trial.
About the Planned Phase 3 Study
With the seven-month Phase 1 data and the launch of the Phase 2
study, the Company is actively preparing for a global randomized,
observer-blind, placebo-controlled Phase 3 pivotal study to
evaluate the efficacy of mRNA-1647 against primary CMV infection.
Moderna has solicited and received Type C meeting feedback from the
FDA on the preliminary design of the pivotal trial, which will
evaluate prevention of primary CMV infection in a population that
includes women of childbearing age. The Company believes this can
be achieved with a trial with no more than 8,000 participants and
feasibility assessments of study sites has already begun across
North America and Europe. After the Phase 2 three-month data are
analyzed, which is expected in the second half of 2020, these data
will inform the dose selection for the Phase 3 pivotal study. The
pivotal trial design will be finalized after discussion with the
FDA and other global health authorities. Manufacturing and planning
are already underway for the pivotal Phase 3 study, which is
expected to start in 2021.
Conference Call
Moderna will host a conference call and webcast on Friday,
January 10, 2020 at 8:00 a.m. ET to discuss these new data. To
access the call, please dial 866-922-5184 (domestic) or
409-937-8950 (international) and refer to conference ID 2684775. A
live webcast of the call will also be available under “Events and
Presentations” in the Investors section of the Moderna website at
https://investors.modernatx.com. The archived webcast will be
available on Moderna’s website approximately two hours after the
conference call and will be available for 30 days following the
call.
About mRNA-1647
mRNA-1647 comprises six mRNAs encoding two antigens in one
vaccine, and is designed to protect against CMV infection. Of the
six mRNAs, five encode the subunits of the CMV pentamer complex and
one mRNA encodes the glycoprotein B (gB) protein, both of which are
highly immunogenic. The pentamer complex is important for CMV entry
into a variety of cells, including epithelial cells, while gB is
important for entry into all susceptible cells including
fibroblasts. A vaccine that produces an immune response against
both pentamer and gB has the potential to prevent CMV entry into a
range of target cell types and thus prevent primary and congenital
infections. Unlike a protein-based vaccine, mRNA-1647 instructs the
body’s own cells to manufacture the antigens, resulting in
functional antigens that mimic those presented to the immune system
by CMV 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 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.1,2 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.3 There
is currently no approved vaccine for the prevention of CMV
infection.
CMV is spread through saliva, breastmilk, 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 seven programs, 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 available 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. More than 1,000 participants have been
enrolled in Moderna’s infectious disease clinical studies.
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 named a top biopharmaceutical
employer by Science for the past five 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, initiating clinical trial sites outside
of the U.S. for mRNA-1647; planning for a pivotal Phase 3 study for
mRNA-1647; exploration of three development candidates for
potential global health; and the Company’s belief that it can
reduce the burden of CMV infection, including in women of
childbearing age. 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: the results and timing of the Phase 2 study; the
results of testing the Phase 3 formulation; the timing of the
proposed Phase 3 study 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 at www.sec.gov.
Except as required by law, Moderna disclaims any intention or
responsibility for updating or revising any forward-looking
statements contained 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 Congenital CMV and Hearing Loss. Centers for Disease Control
and Prevention. Available at:
https://www.cdc.gov/cmv/hearing-loss.html. 2 Schleiss et al.
Progress toward development of a vaccine against congenital
cytomegalovirus infection. Clinical and Vaccine Immunology. 2017;
24(12): e00268-17. 3 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/20200109005801/en/
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
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