YASTEST
Key updates
- QR-010 was observed to be safe and
well-tolerated across all doses in this trial with no serious
adverse events related to treatment.
- A clinically meaningful improvement
of CF respiratory symptoms, as measured by CFQ-R RSS, was observed
in 3 out of 4 multiple dose groups with a mean improvement of 13.0
to 19.2 points compared to placebo. In a pre-defined subgroup of
subjects with a lower lung function at baseline, the mean
improvement was up to 27.5 points compared to placebo.
- Magnitude of the benefit observed in
CFQ-R RSS for these dose groups exceeded the established minimal
clinically important difference of 4.0 points.
- In the same multiple dose groups
a supportive trend of improved lung function was observed up
to 4.0% mean absolute change in ppFEV1compared to placebo. In a
pre-defined subgroup of subjects with a lower lung function at
baseline a mean absolute change in ppFEV1 was observed up to
10.9% compared to placebo.
- After inhaled administration in some
dose groups, QR-010 was detected in the blood.
- ProQR and the Cystic Fibrosis
Foundation Therapeutics intend to expand their partnership to
explore the inhaled oligonucleotide platform to target stop-codon
mutations in CF.
- Management will discuss the top-line
results during a conference call today at 5 pm ET.
LEIDEN, the Netherlands, Sept. 25, 2017 (GLOBE
NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq:PRQR) today announced
positive preliminary top-line results from a Phase 1b safety and
tolerability clinical trial (Study PQ-010-001; NCT02532764) of
QR-010, a novel investigational RNA therapeutic in subjects with
cystic fibrosis (CF). Full data from the trial will be presented at
the North American CF Conference (NACFC) on November 2-4, 2017.
Study PQ-010-001 was a Phase 1b, randomized,
double-blind, placebo-controlled, dose escalation study to evaluate
the safety, tolerability and pharmacokinetics of QR-010 in adult
subjects with CF homozygous for the F508del mutation. This trial
studied 4 dose levels of QR-010 administered via inhalation in 4
single-dose and 4 multiple-dose groups. A number of exploratory
efficacy endpoints were assessed in the multiple dose groups:
respiratory symptoms (as measured by a validated patient-reported
outcome tool, the Cystic Fibrosis Questionnaire-Revised Respiratory
Symptom Score, or CFQ-R RSS), lung function (as measured by
mean absolute change in percent predicted forced expiratory volume
in 1 second, or ppFEV1), sweat chloride test and weight change.
This study included subjects with, on average, a normal lung
function at baseline (mean ppFEV1 86%, range 69-116%). As
therapeutic trials typically study subjects with normal-to-severe
lung function at baseline (ppFEV1 <90%), a subgroup was
pre-defined to analyze the exploratory efficacy endpoints in this
population. The trial recruited 70 participants and was conducted
at 23 sites in 10 countries in Europe and North America.
J. Stuart Elborn, the principal investigator of
the study, Clinical Chair in Respiratory Medicine at Imperial
College, Consultant at Royal Brompton Hospital, and immediate
past-president of the European Cystic Fibrosis Society, added,
"QR-010 exceeded expectations in this study as an innovative
investigational therapy for the treatment of cystic fibrosis for
which the need remains high. The improvements demonstrated in
reduction of respiratory symptoms are very encouraging and
intriguing and of course of enormous importance to people with CF.
The results of this study together with the previous proof of
concept study are strongly supportive of the further development of
QR-010."
Top-Line
Results
In this trial QR-010 was observed to be safe and
well-tolerated across all doses, with an overall safety profile
similar to placebo. There were no serious adverse events related to
treatment. After inhaled administration in some dose groups, QR-010
was detected in the blood. Subjects who received QR-010 in the
6.25, 12.5 and 25 mg multiple dose groups reported fewer
respiratory symptoms after 4 weeks of treatment as measured by the
increased CFQ-R RSS, with mean improvements of 13.0, 19.2 and 14.3
points, respectively, compared to placebo. The effect was more
pronounced in the pre-defined subgroup of subjects with a lower
lung function at the start of the study (baseline
ppFEV1 70-90%) with a mean increase of up to 27.5 points
compared to placebo. These improvements exceeded the minimal
clinically important difference (MCID) of 4.0 points. A supportive
trend of improved lung function was observed in the same multiple
dose groups, as measured by mean absolute change in
ppFEV1 compared to placebo. The trend was stronger in the
subgroup of subjects with a lower lung function at baseline. The
table below summarizes the data per multiple dose group. As
expected, no effect was observed on sweat chloride and weight.
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Per protocol
population
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Pre-defined subgroup of subjects
with
baseline
ppFEV1 70-90%
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CFQ-R RSS
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ppFEV1
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CFQ-R RSS
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ppFEV1
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Groups
(12 doses
over 4
weeks) |
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n |
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|
mean change vs
placebo
(p-value) |
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|
95% CI |
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mean absolute
%
change vs
placebo
(p-value) |
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|
95% CI |
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n |
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|
mean
change vs
placebo
(p-value) |
|
|
95% CI |
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mean absolute %
change vs
placebo
(p-value) |
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95% CI |
6.25 mg |
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6 |
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+13.0 (0.0585) |
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-0.5 ; 26.4 |
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+1.2 (0.7266) |
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-6.0 ; 8.4 |
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3 |
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+23.2 (0.0315) |
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2.4 ; 44.1 |
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+8.0 (0.1613) |
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-3.6 ; 19.5 |
12.5 mg |
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6 |
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+19.2 (0.0072) |
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5.7 ; 32.7 |
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+4.0 (0.2626) |
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-3.2 ; 11.2 |
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4 |
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+27.5 (0.0095) |
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7.9 ; 47.1 |
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+10.9 (0.0461) |
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0.2 ; 21.6 |
25 mg |
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6 |
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+14.3 (0.0399) |
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0.7 ; 27.9 |
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-0.2 (0.9664) |
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-7.3 ; 7.1 |
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5 |
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+20.3 (0.0334) |
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1.9 ; 38.7 |
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+4.7 (0.3410) |
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-5.5 ; 14.8 |
50 mg |
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5 |
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+3.5 (0.6182) |
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-10.7 ; 17.6 |
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-0.6 (0.8749) |
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-8.2 ; 7.0 |
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4 |
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+10.9 (0.2463) |
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-8.4 ; 30.2 |
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+3.7 (0.4745) |
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-7.0 ; 14.3 |
Placebo |
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8 |
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-6.5 |
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-15.3 ; 2.4 |
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-0.8 |
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-5.5 ; 3.9 |
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4 |
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-11.8 |
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-25.5 ; 2.0 |
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-3.8 |
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-11.3; 3.8 |
The Phase 1b study achieved its goals for
evaluation of QR-010 including demonstrating safety and
tolerability across a range of doses, identified a dosing window,
exhibited uptake of the RNA oligonucleotide into circulation
following inhalation, and demonstrated early signals of clinical
efficacy.
"The positive results in the first two clinical
trials of QR-010 significantly increase the confidence that QR-010
has the potential to become an effective treatment of CF. The
improvement in CFQ-R RSS with the supportive FEV1 data as
shown in this Phase 1b trial is very exciting," said Noreen R.
Henig, M.D, Chief Medical Officer at ProQR. "I want to thank the
entire CF community including those living with CF, clinical
investigators, scientists, the CF Foundation, the European CF
Society and the US and European therapeutic development networks
for their unwavering commitment."
Partnership with Cystic
Fibrosis Foundation Therapeutics (CFFT)
ProQR and CFFT entered into a partnership in 2014
to develop QR-010 for people with CF due to the F508del mutation.
The initial partnership included support for the Phase 1b trial as
well as the NPD proof of concept study that reported positive
results in 2016. Based on the results of the clinical trials of
QR-010, ProQR and CFFT intend to expand the partnership to explore
the inhaled oligonucleotide platform for stop-codon mutations (also
called "Class I" mutations) in CFTR. Stop-codon mutations cannot be
targeted with small molecule potentiator or corrector molecules,
and therefore have a high unmet medical need. ProQR intends to
target these mutations using its proprietary
Axiomer® technology, which has shown compelling data in
non-clinical studies, to repair the stop-codon mutations in the
RNA, leading to removal of the premature stop-codon. Approximately
12,000 patients, accounting for 15% of CF patients in the western
world, have a stop-codon mutation leading to a severe form of
CF.
"The results of this Phase 1b trial support
QR-010's potential to be a meaningful therapy for people with
cystic fibrosis," said Daniel A. de Boer, Chief Executive Officer
at ProQR. "With these results in hand we are designing a path
forward for the development of QR-010, either independently or with
a potential partner. Furthermore we are looking forward to
expanding our partnership with the CFFT to explore the inhaled
oligonucleotide platform also for people that have CF due to
stop-codon mutations."
About the PQ-010-001
Trial
The Phase 1b study was a trial designed to assess
safety, tolerability and pharmacokinetics of QR-010. A number of
exploratory efficacy endpoints were assessed in the multiple dose
groups. A total of 4 dose levels were studied: 6.25, 12.5, 25 and
50 mg of QR-010 in solution per dose administered via inhalation
using the PARI eFlow® nebulizer. Subjects eligible to
participate were males and females of 18 years and over with a
ppFEV1 of greater than or equal to 70% at time of
inclusion, homozygous for the F508del mutation, and not taking CFTR
modulator drugs. The study design planned to enroll 8 cohorts of 8
subjects (6 receiving QR-010, 2 receiving placebo). In cohorts 1-4,
a single dose of QR-010 was administered, and in cohorts 5-8 twelve
doses of QR-010 were administered over a 4-week period.
QR-010
Milestones
- Technology for QR-010 in-licensed
from Massachusetts General Hospital in 2012.
- Partnership with the CFF established
to develop QR-010 for patients with the F508del mutation.
- In
vitro proof of concept in three F508del CF assays.
- In
vivo proof of concept in two assays, including nasal
potential difference (NPD).
- Pre-clinical in vitro and in
vivo proof of concept established for efficient inhaled
delivery to the CF diseased lung in collaboration with the
University of North Carolina at Chapel Hill.
- QR-010 granted fast-track status by
the FDA and orphan drug designation from FDA and the European
Commission.
- Program received funding from the
European Union's Horizon 2020 research and innovation
programme.
- Clinical trial PQ-010-002 top-line
data shows significant improvement of CFTR function as measured by
NPD in subjects homozygous for the F508del mutation following
topical administration of QR-010.
- Grant of two key patents, protecting
QR-010 in the US and Europe.
- Preliminary top-line data from
clinical trial PQ-010-001 shows QR-010 is detected in the blood
after inhaled administration, was observed to be safe and
well-tolerated and shows signals of efficacy.
- Full data for PQ-010-001 will be
presented at the NACFC (November 2-4, 2017).
Conference Call and Webcast
Information
ProQR will host a conference call and webcast
today at 5:00 PM Eastern Time (ET) or 11:00 PM Central European
Time (CET). The conference call will be webcast live and a link to
the webcast can be accessed through ProQR's website (www.proqr.com)
and in the "Investors" section under "Events and Presentations". To
ensure a timely connection, it is recommended that users register
at least 15 minutes prior to the scheduled webcast. An archived
webcast will be available on the company's website. To participate
in the conference call, please dial in 5-10 minutes prior to start
time and reference Conference ID
8468989:
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Country |
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Toll Free |
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Direct |
US |
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1 877 280 2296 |
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+1 646 254 3365 |
Netherlands |
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0800 020 2576 |
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+31 (0) 20 713 2789 |
United Kingdom |
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0800 279 4977 |
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+44 (0) 20 3427 1919 |
Germany |
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0800 589 2674 |
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+49 (0) 69 2222 10620 |
Belgium |
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0800 58032 |
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+32 (0) 2 400 3463 |
Switzerland |
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0800 345 603 |
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+41 (0) 44 580 7214 |
France |
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0805 631 580 |
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+33 (0) 1 7677 2222 |
About QR-010
QR-010 is a first-in-class RNA-based
oligonucleotide designed to address the underlying cause of the
disease by targeting the mRNA in CF patients that have the F508del
mutation. The technology was exclusively licensed from
Massachusetts General Hospital. The F508del mutation results in the
production of a misfolded CFTR protein that does not function
normally. QR-010 is a single agent designed to bind to the
defective CFTR mRNA and to restore CFTR function. QR-010 is
designed to be self-administered via an optimized eFlow® Nebulizer
(PARI Pharma GmbH). eFlow® is a small, handheld aerosol
delivery device which nebulizes QR-010 into a mist inhaled directly
into the lungs. QR-010 has been granted orphan drug designation in
the United States and the European Union and fast-track status by
the FDA. The QR-010 project received funding from the European
Union's Horizon 2020 research and innovation programme under grant
agreement No 633545.
About Cystic
Fibrosis
Cystic fibrosis (CF) is the most common fatal
inherited disease in the Western world and affects over 75,000
patients worldwide. In people with CF, a defective CFTR gene causes
a thick buildup of mucus in the lungs, pancreas and other organs.
In the lungs, the mucus clogs the airways and traps bacteria
leading to infections, extensive lung damage and eventually,
respiratory failure. There is no cure for CF. Disease
manifestations lead to a shortened life expectancy with a median
age of death of 30 years. Although over 1,900 CF-causing gene
mutations have been identified, approximately 85% of all CF
patients are affected by the F508del mutation. Among all CF
patients, approximately 50% are homozygous for the F508del
mutation.
About ProQR
ProQR Therapeutics is dedicated to changing lives
through the creation of transformative RNA medicines for the
treatment of severe genetic rare diseases such as cystic fibrosis,
Leber's congenital amaurosis 10 and dystrophic epidermolysis
bullosa. Based on our unique proprietary RNA repair platform
technologies we are growing our pipeline with patients and loved
ones in mind.
*Since 2012*
FORWARD-LOOKING
STATEMENTS
This press release contains forward-looking
statements. All statements other than statements of historical fact
are forward-looking statements, which are often indicated by terms
such as "anticipate," "believe," "could," "estimate," "expect,"
"goal," "intend," "look forward to", "may," "plan," "potential,"
"predict," "project," "should," "will," "would" and similar
expressions. Forward-looking statements are based on management's
beliefs and assumptions and on information available to management
only as of the date of this press release. These forward-looking
statements include, but are not limited to, statements regarding
QR-010, including its clinical development and therapeutic
potential, including future development plans, and statements
regarding the partnership with CFFT. Our actual results could
differ materially from those anticipated in these forward-looking
statements for many reasons, including, without limitation, risks
associated with our clinical development activities, including that
positive results observed in our prior and ongoing studies may not
be replicated in later trials or guarantee approval of any product
candidate by regulatory authorities, that a Fast Track designation
by the FDA may not actually lead to a faster development,
regulatory review or approval process, and that we may not be able
to realize the potential benefits of orphan drug exclusivity,
manufacturing processes and facilities, regulatory oversight,
product commercialization, intellectual property claims, and the
risks, uncertainties and other factors in our filings made with the
Securities and Exchange Commission, including certain sections of
our annual report filed on Form 20-F. Given these risks,
uncertainties and other factors, you should not place undue
reliance on these forward-looking statements, and we assume no
obligation to update these forward-looking statements, even if new
information becomes available in the future.
ProQR Therapeutics
N.V.:
Media Contact:
Sariette Witte
T: +31 6 2970 4513 (NL)
T: + 1 213 261 8891 (US)
pr@proqr.com
Investor
Contact:
Bonnie Ortega
T: +1 858 245 3983
ir@proqr.com
This
announcement is distributed by Nasdaq Corporate Solutions on behalf
of Nasdaq Corporate Solutions clients.
The issuer of this announcement warrants that they are solely
responsible for the content, accuracy and originality of the
information contained therein.
Source: ProQR Therapeutics N.V. via Globenewswire
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