WARRINGTON, Pa., Nov. 12, 2015 /PRNewswire/ -- Discovery
Laboratories, Inc. (NASDAQ: DSCO), a specialty biotechnology
company focused on developing aerosolized KL4 surfactant therapies
for respiratory diseases, today reported top line data from its
recently completed AEROSURF® phase 2a clinical program in premature
infants 29 to 34 week gestational age (GA) receiving nasal
continuous positive airway pressure (nCPAP) for respiratory
distress syndrome (RDS). The two-part program enrolled a
total of 80 premature infants including 40 infants in five AEROSURF
dose groups and 40 control infants on nCPAP alone. The
Company previously announced top line data from the initial trial
in May 2015. The Company is now
reporting data on the overall phase 2a program in premature infants
29 to 34 week GA including the recently completed phase 2a
expansion study. The data are encouraging and
suggest that aerosolized KL4 surfactant delivered to
premature infants with RDS is generally safe and well tolerated and
may decrease nCPAP failure and the need for intubation. The
Company is now advancing AEROSURF to a phase 2b clinical trial
beginning with enrollment of premature infants 29 to 32 week
GA.
Discovery Labs' management will host a conference call and
live webcast, with a slide presentation including data from the
clinical trial, today at 8:00 a.m. Eastern time to review and
discuss the results of the trial. See below for details of
the call.
Key objectives of the program were achieved, including
(1) the primary objective of evaluating the safety and
tolerability of aerosolized KL4 surfactant, compared to nCPAP
alone; (2) proof of concept for the Company's proprietary
technology platform based on physiological data suggesting that
aerosolized KL4 surfactant is being delivered into the lungs of
premature infants; and, (3) acceptable performance of the novel
aerosol delivery technology in the neonatal intensive care unit
(NICU). Key observations from the data include:
- Overall, the safety and tolerability profile of the AEROSURF
group in this phase 2a program was generally comparable to the
control group. All reported adverse events and serious adverse
events were those that are common and expected among premature
infants with RDS. Based on the safety and tolerability profile
observed in the program, the Company is progressing to the AEROSURF
phase 2b clinical trial.
- Data suggest that AEROSURF may be reducing the incidence of
nCPAP failure (the need for intubation and delayed surfactant
therapy). Through 72 hours after the start of treatment, AEROSURF
treated patients, predominantly receiving a single dose, had lower
rates of nCPAP failure compared to control in each of the last
three dose groups studied. nCPAP failure rates were 53% in the
control group compared to 38%, 29% (excluding one patient who was
inappropriately enrolled) and 38% in the 45, 60 and 90 minute
AEROSURF dose groups, respectively.
The Company has focused its
planning for the phase 2b clinical trial on the 45 and 60 minute
dose groups. The combined data for these groups indicate
that, through 72 hours after the start of treatment, AEROSURF
treated patients had a 33% nCPAP failure rate compared to 53% in
the control group. This represents a 20% absolute reduction
or a 38% relative reduction in nCPAP failure compared to
control.
- The phase 2a program in premature infants 29 to 34 week GA has
provided a foundation and direction for the AEROSURF phase 2b trial
in premature infants 26 to 32 week GA. The Company expects to
initiate the phase 2b trial in the fourth quarter of 2015. The
phase 2b trial will include the ability to administer repeat doses,
if necessary. Enrollment will begin with premature infants 29 to 32
week GA, followed by enrollment of premature infants 26 to 28 week
GA.
"Premature infants with RDS are born with immature lungs and are
frequently unable to produce their own endogenous surfactant for up
to 48 to 72 hours of life. With AEROSURF, we potentially have
an opportunity to administer aerosolized KL4 surfactant
non-invasively to support premature infants until they are able to
produce their own surfactant." commented Steve Simonson, M.D., Discovery Labs' Chief
Development Officer. "The data from the phase 2a program to
date are very encouraging. We are seeing signals that suggest
our goal of reducing nCPAP failures and intubations with AEROSURF
appears achievable. If we are successful, we believe AEROSURF
will represent a transformational change in the management of
RDS."
Phase 2a Clinical Program in Premature Infants 29 to 34 Weeks
GA
Study Design
The phase 2a clinical studies were multicenter, randomized,
open-label, controlled studies in 80 premature infants 29 to 34
weeks GA receiving nCPAP for RDS, and designed to evaluate the
safety and tolerability of aerosolized KL4 surfactant administered
in five dose groups (15, 30, 45, 60 and 90 minute), compared to
infants receiving nCPAP alone. In addition to safety and
tolerability, another objective of the study was to establish proof
of concept for the Company's proprietary technology platform based
on physiological data suggesting that aerosolized KL4 surfactant is
being delivered into the lung of premature infants, and acceptable
performance of the aerosol delivery technology in the NICU.
Safety and Tolerability
Overall, the safety and tolerability profile of the AEROSURF
group in the studies was generally comparable to the control
group. All reported adverse events and serious adverse events
were those that are common and expected among this fragile patient
population. The most common adverse events observed included
neonatal jaundice, constipation, apnea and anemia. The most
common serious adverse events were
air leaks (pneumothorax and pneumomediastinum). The incidence
of adverse events and serious adverse events in the AEROSURF and
control groups were generally comparable and there was no pattern
observed of increasing adverse events or serious adverse events
with increasing doses of AEROSURF.
Air leaks (including pneumothorax, pneumomediastinum and
pulmonary interstitial emphysema) were the most common complication
of prematurity in both the AEROSURF and control groups. There
were a total of nine patients with air leaks in the AEROSURF group
and seven patients with air leaks in the control group. One
AEROSURF treated infant was found to have an air leak prior to
study drug administration. One other infant in the AEROSURF
group was inappropriately enrolled in the study, received only a
brief exposure to study drug and has been excluded from the
analysis of all of the physiological evaluations below. The
incidence of air leaks was not unexpected and comparable to what
has been reported in the literature (23-47%) for infants in this
age group (Dargaville et al., 2013). All air leaks
were resolved without complication and there was no pattern of
increased incidence of air leaks with increasing AEROSURF dose.
Regarding tolerability of AEROSURF administration, the patient
interface was well tolerated. Peri-dosing events, which are
common in the endotracheal administration of surfactants currently,
were infrequent in the AEROSURF group.
Physiological Evaluation
In exploratory analyses of certain safety and tolerability
measures to assess whether aerosolized KL4 surfactant was being
delivered to the lungs of premature infants and potentially having
a physiological effect, measurements of gas exchange in the lungs
and the timing of or need for endotracheal intubation and delayed
(rescue) surfactant therapy due to nCPAP failure were evaluated in
both the AEROSURF and control groups.
Requirement for Invasive Rescue Therapy due to nCPAP
failure
Parameters associated with delayed surfactant therapy and nCPAP
failure were assessed as part of the safety and tolerability
profile of AEROSURF. These data were also used to evaluate
whether AEROSURF had an impact on the need for intubation and
delayed surfactant therapy due to nCPAP failure.
Overall, the nCPAP failure rates through 72 hours after the
start of treatment or randomization to the control group were 63%
(15 min), 75% (30 min), 38% (45 min), 29% (60 min) and 38% (90 min)
for the five AEROSURF groups compared to 53% in the control
group. AEROSURF treatment of 45 minutes and greater
(primarily single doses) appears to be associated with lower rates
of nCPAP failure representing a 28% (45 and 90 min) and 45% (60
min) relative reduction in nCPAP failure compared to control.
These data, combined with the favorable safety profile, have
formed the basis for dose selection in the phase 2b program.
The Company has focused on two dose groups (45 and 60 minutes) to
define the appropriate upper dose to take into the phase 2b
study. In doing so, the Company combined the data in the 45
min and 60 min AEROSURF dose groups (n=15) and assessed nCPAP
failure compared to the control group (n=40). The results
suggest that: (i) at six hours after the start of treatment or
randomization to the control group, 18% of control patients
required intubation and delayed surfactant therapy compared to no
AEROSURF patients; and, (ii) at 72 hours after the start of
treatment or randomization to the control group, 53% in the control
group required intubation and delayed surfactant therapy compared
to 33% of patients in the AEROSURF group. This represents a
20% absolute reduction or a 38% relative reduction in nCPAP failure
compared to control.
Gas Exchange
Gas exchange parameters were assessed as part of the safety and
tolerability profile of AEROSURF. No safety signals were
observed with respect to gas exchange. The fraction of
inspired oxygen (FiO2) required by an infant is considered a key
measurement of how well the lung is functioning to oxygenate the
blood. Healthy lungs can achieve appropriate blood oxygen
saturation breathing room air; however, premature infants with RDS
frequently require supplemental oxygen. Carbon dioxide levels
in the blood (PCO2) are considered a measure of respiratory
function and how efficiently the lungs eliminate carbon dioxide
(CO2) from the bloodstream.
The data for all five dose groups suggest that AEROSURF is
associated with a decrease in FiO2 shortly after initiation of
treatment and numerically greater change in PCO2 levels compared to
control. The changes in these parameters are consistent with
the effects that one would expect to see with a surfactant
delivered to the lung.
Performance of the Novel Aerosol Delivery
Technology
The aerosol delivery technology performed as designed by
delivering a high-output, dense aerosol stream that met all output
specifications. During the course of the phase 2a trial,
there were no device-related adverse events. Overall, the
device was well accepted by NICU personnel at all study sites.
The clinical trials in 29 to 34 week GA premature infants was
supported, in part, by a $1.9 million
Phase II award of a $2.4 million Fast
Track Small Business Innovation Research (SBIR) grant from the
National Heart, Lung, and Blood Institute (NHLBI) of the National
Institutes of Health (NIH) under award number
4R44HL107000-02. The content of this press release is solely
the responsibility of the Company and does not necessarily
represent the official views of the National Institutes of
Health.
Conference Call and Webcast Details
Discovery
Labs' management will host a conference call and live webcast, with
a slide presentation including data from the clinical trial, today
at 8:00 a.m. Eastern time to review and discuss the results of
the trial. The live webcast and archive of the conference
call can be accessed at
http://discoverylabs.investorroom.com/events.
For "listen-only" participants and those who wish to take part
in the question and answer portion of the call, dial (888) 346-0767
(domestic) or (412) 902-4251 (international). After placing
the call, request to be joined into the Discovery Labs conference
call. A replay of the conference call will be accessible
through November 20, 2015 by dialing
(877) 344-7529 (domestic) or (412) 317-0088 (international) and
referencing conference ID number 10076116.
About AEROSURF®
Premature infants
with severe RDS currently are treated with surfactants that can
only be administered by endotracheal intubation supported with
mechanical ventilation, invasive procedures that may each result in
serious respiratory conditions and other complications. To
avoid such complications, many neonatologists treat infants with
less severe RDS by less invasive means, typically nCPAP.
Unfortunately, a significant number of premature infants on nCPAP
will respond poorly (an outcome referred to as nCPAP failure) and
may require delayed surfactant therapy. Since neonatologists
currently cannot predict which infants will experience nCPAP
failure, neonatologists are faced with difficult choices in
treating infants with less severe RDS. This is because the
medical outcomes for those infants who experience nCPAP failure and
receive delayed surfactant therapy may be less favorable than the
outcomes for infants who received surfactant therapy in the first
hours of life.
AEROSURF is a novel, investigational drug/device product that
combines the Company's proprietary KL4 surfactant and its
aerosolization technologies. AEROSURF is being developed to
potentially reduce or eliminate the need for endotracheal
intubation and mechanical ventilation in the treatment of premature
infants with respiratory distress syndrome (RDS). With
AEROSURF, neonatologists may potentially administer aerosolized KL4
surfactant to premature infants supported by nCPAP, without
subjecting them to invasive endotracheal intubation and mechanical
ventilation (each of which can result in serious respiratory
conditions and other complications), which are currently required
to administer surfactant therapy to premature infants. By
enabling delivery of aerosolized KL4 surfactant using less invasive
procedures, AEROSURF, if approved, has the potential to
address a serious unmet medical need, provide transformative
clinical and pharmacoeconomic benefits, and enable the treatment of
a significantly greater number of premature infants with RDS who
could benefit from surfactant therapy but are currently not
treated.
Currently in the U.S., the Company estimates that approximately
120,000 to 150,000 premature infants could benefit from surfactant
therapy. However, due to the risks associated with
endotracheal intubation and mechanical ventilation, only
approximately 50,000 to 60,000 of these infants currently are
treated with surfactants as the initial therapy for severe
RDS. The remaining infants with less severe RDS are usually
supported with nCPAP alone. However, a large percentage of
these infants are not adequately supported with nCPAP alone (an
outcome referred to as nCPAP failure) and thereafter may require
delayed surfactant therapy administered by endotracheal intubation
and mechanical ventilation
About Discovery Labs
Discovery Laboratories,
Inc. is a specialty biotechnology company focused on developing
aerosolized KL4 surfactant therapies for respiratory
diseases. Surfactants are produced naturally in the lung and
are essential for normal respiratory function and survival.
If surfactant deficiency or degradation occurs, the air sacs in the
lungs can collapse, resulting in severe respiratory diseases and
disorders. Discovery Labs' technology platform includes a
novel synthetic peptide-containing (KL4) surfactant, that is
structurally similar to pulmonary surfactant, and proprietary drug
delivery technologies being developed to enable efficient delivery
of aerosolized KL4 surfactant. Discovery Labs believes that
its proprietary technology platform makes it possible, for the
first time, to develop a significant pipeline of aerosolized
surfactant products to address a variety of respiratory diseases
for which there frequently are few or no approved therapies.
For more information, please visit the Company's website at
www.Discoverylabs.com.
Forward-Looking Statements
Securities Litigation Reform Act of 1995. These
forward-looking statements are subject to risks and uncertainties
that could cause actual results to differ materially from the
statements made. Examples of such risks and uncertainties,
including those affecting Discovery Labs' ability successfully to
complete its development programs and realize the potential
benefits of its RDS product portfolio, are described in Discovery
Labs' filings with the Securities and Exchange Commission,
including the most recent reports on Forms 10-K, 10-Q and 8-K, and
any amendments thereto. Any forward-looking statement in this
release speaks only as of the date on which it is made.
Discovery Labs assumes no obligation to update or revise any
forward-looking statements.
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SOURCE Discovery Laboratories, Inc.
