- Topline data from the Resolve(TM)
Phase 3 trial did not meet pre-specified efficacy objectives
- The attack rate for the Phase 3
primary objective was approximately 25% of that observed in Phase 2
trial
- Topline data from our Phase 2
rollover trial suggest improved vaccine efficacy from a second year
of dosing
Management
will host a conference call at 5:00 pm ET time today
GAITHERSBURG, Md., Sept. 15, 2016
(GLOBE NEWSWIRE) -- Novavax, Inc., (Nasdaq:NVAX) today announced
topline data from two clinical trials of its RSV F-protein
recombinant nanoparticle vaccine candidate (RSV F Vaccine) in older
adults. The Resolve(TM) trial, a Phase 3 trial of our RSV F
Vaccine in 11,856 older adults (60 years of age and older), did not
meet the pre-specified primary or the secondary efficacy
objectives, and did not demonstrate vaccine efficacy. Consistent
with our previous clinical experience, the vaccine was well
tolerated.
Phase 3 Resolve(TM)
Trial
The trial was a randomized,
observer-blinded, placebo-controlled trial conducted at 60 sites in
the United States. The primary objective of the Resolve trial was
to demonstrate efficacy in the prevention of moderate-severe
RSV-associated lower respiratory tract disease (RSV msLRTD), as
defined by the presence of multiple lower respiratory tract
symptoms. The secondary objective of the trial was to demonstrate
efficacy of the RSV F Vaccine in reducing the incidence of all
symptomatic respiratory disease due to RSV (RSV ARD). Finally, the
trial also evaluated the safety of the unadjuvanted, 135 microgram
dose of the RSV F Vaccine compared to placebo.
Topline efficacy results of the
trial are shown in the following table:
Summary of Primary and Secondary
Objectives - Vaccine Efficacy |
|
Number of Participants - ITT Population
(11,856) |
Primary and
Secondary
Objectives |
Placebo
(5,935) |
Vaccine
(5,921) |
Vaccine
Efficacy (CI) |
P-Value |
Primary: RSV msLRTD, N(%) |
26 (0.44%) |
28 (0.47%) |
-7.9 % (-84, 37) |
0.78 |
Secondary: RSV ARD, N(%) |
117 (1.97%) |
102 (1.72%) |
12.6 % (-14, 33) |
0.32 |
"We are both surprised and
disappointed by the outcome of the Resolve trial, which we recently
unblinded. Our initial analyses and review of the key aspects of
the trial do not indicate issues with trial execution, data
collection, data integrity, or drug product quality. We expect to
have preliminary immunogenicity data in the coming weeks to further
our understanding of the trial results," said Gregory Glenn M.D.,
President, Research and Development. "Historically, annual seasonal
RSV ARD attack rates between 3% and 7% have been observed in older
adults1. In our Phase 2 trial, we observed an RSV ARD attack rate
of 4.9% and an RSV msLRTD attack rate of 1.8%. In contrast, we
observed an RSV ARD attack rate of 2.0% and an msLRTD attack rate
of 0.4% in our Phase 3 trial. These attack rates indicate a mild
RSV season in older adults this year. We are continuing to
investigate potential root causes that could have impacted the
outcome of this trial. We continue to believe that there is a path
forward for our RSV vaccine and that there is an important unmet
need for an RSV vaccine in older adults."
Phase 2 Rollover
Trial
Novavax also reported topline
results from the Phase 2 rollover clinical trial of its RSV F
Vaccine in older adults.
The trial was a randomized,
observer-blinded, placebo-controlled rollover trial which enrolled
1,329 older adults from the prior Phase 2 trial, conducted at the
same 10 sites in the United States. The primary objectives of the
trial evaluated safety and serum anti-F IgG antibody concentrations
in response to immunization with the RSV F Vaccine. The exploratory
objectives of the trial evaluated the efficacy of a second annual
dose of the RSV F Vaccine in the prevention of RSV ARD and RSV
msLRTD. Participants previously randomized to receive 135 microgram
RSV F Vaccine or placebo were re-enrolled and re-randomized in the
current trial to receive either 135 microgram RSV F Vaccine or
placebo. This resulted in analysis of four separate trial arms: a)
participants receiving a placebo in both the first trial and second
trial; b) participants receiving RSV F Vaccine in the first trial
and placebo in the second trial (Vaccine-Placebo); c) participants
receiving placebo in the first trial and RSV F Vaccine in the
second trial (Placebo-Vaccine); and d) participants receiving RSV F
Vaccine in both the first trial and second trial
(Vaccine-Vaccine).
Topline results of the trial are
shown in the following tables:
Summary of Geometric Mean Titer for
Anti-F by Visit - ITT Population |
|
Number of Participants
(1,329) |
|
Placebo
(2014/15)
Placebo (2015/16)
(N = 333) |
Vaccine (2014/15)
Placebo (2015/16)
(N = 328) |
Placebo (2014/15)
Vaccine (2015/16)
(N = 337) |
Vaccine (2014/15)
Vaccine (2015/16)
(N = 331) |
Day 0 (baseline)
N |
|
333 |
|
|
327 |
|
|
336 |
|
|
329 |
|
GMEU |
|
1012.8 |
|
|
2293.6 |
|
|
962.9 |
|
|
2267.3 |
|
95% CI |
|
(922.0,1112.5 |
) |
|
(2091.8, 2514.9 |
) |
|
(869.0,1067.0 |
) |
|
(2076.4, 2475.8 |
) |
|
Day 28 N |
|
332 |
|
|
325 |
|
|
333 |
|
|
327 |
|
GMEU |
|
1019.3 |
|
|
2188.7 |
|
|
6071.2 |
|
|
4489.3 |
|
95% CI |
|
(928.6, 1119.0 |
) |
|
(2005.0, 2389.2 |
) |
|
(5526.9, 6669.0 |
) |
|
(4137.7, 4870.7 |
) |
GMEU:
geometric mean ELISA units |
|
Gregory Glenn, M.D., said, "The
rollover trial demonstrated immunogenicity in all active vaccine
recipients. As shown in the table above, there was a 6-fold
increase in anti-F IgG in the Placebo-Vaccine arm, consistent with
the Phase 2 efficacy trial. There was higher anti-F IgG at baseline
in the Vaccine-Vaccine arm compared to the Placebo-Vaccine arm.
Further, the Vaccine-Vaccine arm showed a greater than 2-fold
increase in anti-F IgG from the higher baseline. We observed
similar low attack rates and absence of efficacy of a single
immunization in this trial as was observed in Phase 3 Resolve
trial, although we did observe that a second season immunization
could provide efficacy. The event rate comparisons made to either
placebo groups suggested that the second season immunization was
protective, even in a year with a very low attack rate. Further
understanding of these data may come forth with full evaluation of
the immune responses."
Summary of Exploratory Efficacy
Objective+ |
|
Number of Participants
(1,329) |
|
Placebo
(2014/15)
Placebo (2015/16)
(N = 333) |
Vaccine (2014/15)
Placebo (2015/16)
(N = 328) |
Placebo (2014/15)
Vaccine (2015/16)
(N = 337) |
Vaccine (2014/15)
Vaccine (2015/16)
(N = 331) |
RSV ARD (%) |
8 (2.4%) |
7 (2.1%) |
11 (3.3%) |
2 (0.6%)* |
RSV ARD Vaccine Efficacy |
|
|
11 |
% |
|
-36 |
% |
|
75 |
% |
msLRTD (%) |
1 (0.3%) |
2 (0.6%) |
2 (0.6%) |
|
0 |
|
*p-value
= 0.079; msLRTD was not calculated due to low N value |
+all data
in table is not significant (p-value > 0.05); preliminary N |
|
|
|
|
|
|
|
"While the results from the
Resolve trial are unexpected, we continue to believe in our
technology and product candidates based on the totality of the data
from our RSV F Vaccine franchise," said Stanley C. Erck, President
and CEO. "We expect to gain a better understanding of the data from
both the Phase 2 rollover and Phase 3 trials as we further analyze
and review them internally, as well as with our investigators and
potential partners. We intend to provide a more in-depth update at
our investor and analyst meeting on October 11, 2016."
Conference call
Novavax management will host a
conference call at 5:00 p.m. ET. The dial-in number for the
conference call is 877-212-6076 (U.S. or Canada) or 707-287-9331
(International), passcode 80163880. A webcast of the conference
call can also be accessed via a link on the home page of the
Novavax website (novavax.com) or through the "Investor
Info"/"Events" tab on the Novavax website. Presentation
slides will be available via the webcast link.
A replay of the conference call
will be available starting at 7:30 p.m. on September 15, 2016 until
midnight September 20, 2016. To access the replay by telephone,
dial 855-859-2056 (Domestic) or 404-537-3406 (International) and
use passcode 80163880. The replay will also be available as a
webcast and can be found on the "Investor Info"/"Events" on the
Novavax website.
About RSV
Respiratory syncytial virus,
commonly referred to as RSV, is a respiratory infectious disease
that causes serious infection of the respiratory tract, similar to
influenza. For some, RSV may progress in severity, and lead to
hospitalization or even death. The spread of RSV occurs annually,
with an incidence rate of 2.5 million infections per year
in the United States, RSV is increasingly being recognized as
a significant cause of morbidity and mortality in the population of
64 million older adults.1,2 Each year, RSV is responsible for
approximately 207,000 hospitalizations and 16,000 deaths among
adults older than 65.3 Annually, there are approximately
900,000 medical interventions directly caused by RSV
disease.4,5 Currently, there is no approved RSV vaccine
available.
About
Novavax
Novavax, Inc. (Nasdaq:NVAX) is a
clinical-stage vaccine company committed to delivering novel
products to prevent a broad range of infectious diseases. Its
recombinant nanoparticles and Matrix-M(TM) adjuvant technology are
the foundation for ground-breaking innovation that improves global
health through safe and effective vaccines. Additional information
about Novavax is available on the company's
website, novavax.com.
References
1. A.R. Falsey et al. Respiratory syncytial virus
infection in elderly and high-risk adults. N
Engl J Med. 2005; 352:1749-59.
2. A.R. Falsey et al. Respiratory
syncytial virus and influenza A infections in the hospitalized
elderly. J. Infect
Dis. 1995; 172:389-94.
3. K. Widmer et al. Rates of hospitalizations
for respiratory syncytial virus, human metapneumovirus, and
influenza virus in older adults. J Infect
Dis. 2012; 206: 56-62.
4. K. Widmer et al. Respiratory syncytial virus
& human metapneumovirus-associated emergency department and
hospital burden in adults. Influenza and
Other Respiratory Viruses. 2014; 8(3): 347-352.
Forward-Looking Statements
Statements herein relating to the
future of Novavax and the ongoing development of its vaccine and
adjuvant products are forward-looking statements. Novavax cautions
that these forward looking statements are subject to numerous risks
and uncertainties, which could cause actual results to differ
materially from those expressed or implied by such statements.
These risks and uncertainties include those identified under the
heading "Risk Factors" in the Novavax Annual Report on Form 10-K
for the year ended December 31, 2015 as filed with the Securities
and Exchange Commission (SEC). We caution investors not to place
considerable reliance on the forward-looking statements contained
in this press release. You are encouraged to read our filings with
the SEC, available at sec.gov, for a discussion of these and other
risks and uncertainties. The forward-looking statements in this
press release speak only as of the date of this document, and we
undertake no obligation to update or revise any of the statements.
Our business is subject to substantial risks and uncertainties,
including those referenced above. Investors, potential investors,
and others should give careful consideration to these risks and
uncertainties.