- Statistically Significant Improvement in Percent Predicted
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Versus
Placebo at Week 24 (Primary Endpoint) and Week 48 (Secondary
Endpoint)
- Statistically Significant Improvement in St. George’s
Respiratory Questionnaire (SGRQ) Total Score at Week 24 (Secondary
Endpoint)
- 97% of Patients Completed Double-Blind Treatment Through Week
48 with No Trial Drug Related Adverse Events Leading to
Discontinuation
- 100% of Patients Completing the 48-Week Double-Blind Period
Elected to Participate in the 96-Week Open-Label Period
- Company Plans to Complete BLA Submission in 1H 2025
- Company to Host Webcast Conference Call Today, June 26, 2024 at
8:00am ET
Savara Inc. (Nasdaq: SVRA) (the Company), a clinical stage
biopharmaceutical company focused on rare respiratory diseases,
today announced positive results from the pivotal, Phase 3 IMPALA-2
clinical trial. IMPALA-2 is a 48-week, randomized, double-blind,
placebo-controlled trial assessing the efficacy and safety of
molgramostim 300 mcg administered once daily by inhalation with
matching placebo in adult patients with aPAP (NCT04544293).
Molgramostim is an inhaled form of recombinant human
granulocyte-macrophage colony-stimulating factor (GM-CSF).
The trial met its primary endpoint. The treatment difference
between molgramostim and placebo for mean change from baseline to
Week 24 in hemoglobin-adjusted percent predicted DLCO achieved
statistical significance. This statistically significant treatment
difference was sustained at Week 48, a secondary endpoint, which
demonstrated durability of effect.
The treatment difference between molgramostim and placebo for
mean change from baseline to Week 24 in SGRQ Total Score achieved
statistical significance. Two additional secondary endpoints
reached nominal significance: SGRQ Activity Score at Week 24 and
exercise capacity using a treadmill test at Week 48.
“There is a high unmet need for effective, disease-specific
pharmacotherapy for autoimmune PAP,” said Bruce Trapnell, M.D.,
Professor of Medicine and Pediatrics at the University of
Cincinnati College of Medicine and the Lead Clinical Investigator
of the IMPALA-2 trial. “Patients typically experience
breathlessness, which begins slowly and progresses over time, often
accompanied by cough and fatigue, and in some patients, serious
infections, pulmonary fibrosis, and respiratory failure requiring
lung transplantation. With convincing data from two large clinical
trials, the evidence now clearly demonstrates molgramostim has the
potential to be a safe and efficacious treatment option for these
patients. This is a momentous day for the aPAP community.”
IMPALA-2 Top Line Efficacy Results
(Full Analysis Set, n=164):
Lung Function Efficacy Endpoints Molgramostim 300 mcg
meanchange from baseline compared toplacebo P-value
Primary: DLCO % predicted (Hgb-adjusted) at Week 24
6.00
0.0007
Secondary: DLCO % predicted (Hgb-adjusted) at Week 48
6.90
0.0008
Secondary Efficacy Endpoints Measuring Clinical Benefit
Molgramostim 300 mcg meanchange from baseline to Week 24compared
to placebo P-value Molgramostim 300 mcg meanchange
from baseline to Week48 compared to placebo P-value SGRQ
Total Score (points)
-6.59
0.0072
-4.87
0.1046
SGRQ Activity Score (points)
-7.81
0.0149
-5.99
0.1216
Exercise Capacity (peak METs)
0.41
0.0845
0.55
0.0234
SGRQ is a patient-reported outcomes instrument that measures
overall health, daily life, and a patient’s perceived well-being.
SGRQ Activity assesses the patient’s ability to carry out daily
physical activity. With SGRQ, a negative change from baseline
corresponds to improvement. Exercise capacity as measured by a
treadmill is a cardiorespiratory health (CRH) measurement.
Molgramostim was well tolerated. The frequency of adverse events
was generally similar between treatment groups. Two patients (2.5%)
discontinued molgramostim treatment due to adverse events, both of
which were considered unrelated to trial drug. The most commonly
reported adverse events in the molgramostim group were COVID-19,
cough, and pyrexia, with COVID-19 occurring more frequently with
molgramostim than with placebo.
IMPALA-2 Top Line Safety Results
(Safety Analysis Set, n=164):
Treatment Related Adverse Events Molgramostim(N=81)n
(%) Placebo(N=83)n (%) Any
69 (85)
71 (86)
Most common
COVID-19
18 (22)
8 (10)
Cough
17 (21)
18 (22)
Pyrexia
11 (14)
9 (11)
Nasopharyngitis
11 (14)
7 (8)
Arthralgia
9 (11)
7 (8)
Headache
9 (11)
7 (8)
Diarrhea
9 (11)
2 (2)
Alveolar proteinosis
4 (5)
12 (14)
Serious
14 (17)
20 (24)
Treatment related
20 (25)
16 (19)
“The IMPALA-2 results not only met, but exceeded, our
expectations, validating our hypothesis that molgramostim provides
clear, durable improvement in gas exchange, and beyond that,
clinical benefits that positively impact quality of life for aPAP
patients," said Matt Pauls, Chair and CEO, Savara. "The strong
efficacy data and favorable benefit-risk profile potentially
position molgramostim to be the first and only approved therapeutic
for aPAP in the U.S. and Europe. We extend our gratitude to the
patients and their families, clinicians, and site personnel for
their contributions and ongoing participation in the largest
clinical trial in aPAP. We look forward to analyzing the full data
from IMPALA-2 and anticipate submitting it for presentation at a
scientific conference later this year.”
Molgramostim has been granted Orphan Drug, Fast Track, and
Breakthrough Therapy designation from the U.S. Food and Drug
Administration, Orphan Drug designation from the European Medicines
Agency and Innovative Passport and Promising Innovative Medicine
designation from the UK's Medicines and Healthcare Products
Regulatory Agency for the treatment of aPAP.
Conference Call
Savara management will host a conference call and live
audiovisual webcast to discuss the IMPALA-2 results at 8:00am ET
today. To access the live webcast of the call with slides please
click here or visit the "Events & Presentations" section of
Savara’s website. To access the call by phone, please use this
registration link, and you will be provided with dial in details. A
replay of the webcast will be available approximately 24 hours
after the conclusion of the call and archived for 90 days under the
"Events & Presentations" section of the Company's website at
www.savarapharma.com.
About the IMPALA-2 Trial
IMPALA-2 is a global, pivotal, Phase 3, 48-week, randomized,
double-blind, placebo-controlled clinical trial designed to compare
the efficacy and safety of molgramostim 300 mcg administered once
daily by inhalation with matching placebo in patients with aPAP.
The trial is being conducted at 43 clinical trial sites across 16
countries in the U.S., Canada, Japan, South Korea, Australia and
countries in Europe, including Turkey. The primary efficacy
assessment is diffusing capacity of the lungs for carbon monoxide
(DLCO), a gas exchange measure, and the primary endpoint is change
from baseline to Week 24 in percent predicted DLCO, with a
secondary endpoint of change from baseline to Week 48 in percent
predicted DLCO. Three additional secondary efficacy variables
evaluate clinical measures of direct patient benefit: St. George’s
Respiratory Questionnaire (SGRQ) Total Score, SGRQ Activity Score,
and exercise capacity using a treadmill test, with each endpoint
measured at Weeks 24 and 48. The primary time point for efficacy
assessments is at Week 24; however, efficacy was assessed through
Week 48 to evaluate durability of effect. Safety was assessed
through Week 48. Pending applicable regulatory and ethics committee
approvals, following the 48-week double-blind treatment period
patients may continue in a 96-week open-label period and receive
molgramostim 300 mcg administered once daily.
About aPAP
Autoimmune PAP is a rare lung disease characterized by the
abnormal build-up of surfactant in the alveoli (or air sacs) of the
lungs. Surfactant consists of proteins and lipids and is an
important physiological substance that lines the alveoli to prevent
them from collapsing. In a healthy lung, excess surfactant is
cleared and digested by immune cells called alveolar macrophages.
Alveolar macrophages need to be stimulated by
granulocyte-macrophage colony-stimulating factor (GM-CSF) to
function properly in clearing surfactant, but in autoimmune PAP,
GM-CSF is neutralized by antibodies against GM-CSF, rendering the
macrophages unable to adequately clear surfactant. As a result, an
excess of surfactant accumulates in the alveoli, causing impaired
gas exchange, resulting in clinical symptoms of shortness of
breath, often with cough and frequent fatigue. Patients may also
experience episodes of fever, chest pain, or coughing up blood,
especially if secondary lung infection develops. In the long-term,
the disease can lead to serious complications, including lung
fibrosis and the need for a lung transplant.
About Savara
Savara is a clinical stage biopharmaceutical company focused on
rare respiratory diseases. Our lead program, molgramostim nebulizer
solution, is an inhaled granulocyte-macrophage colony-stimulating
factor (GM-CSF) in Phase 3 development for autoimmune pulmonary
alveolar proteinosis (aPAP). Molgramostim is delivered via an
investigational eFlow® Nebulizer System (PARI Pharma GmbH)
specifically developed for inhalation of a large molecule. Our
management team has significant experience in rare respiratory
diseases and pulmonary medicine, identifying unmet needs, and
effectively advancing product candidates to approval and
commercialization. More information can be found at
www.savarapharma.com. (X, formerly known as Twitter: @SavaraPharma,
LinkedIn: www.linkedin.com/company/savara-pharmaceuticals/).
Forward-Looking Statements
Savara cautions you that statements in this press release that
are not a description of historical fact are forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements may be identified by
the use of words referencing future events or circumstances such as
“expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,”
among others. Such statements include, but are not limited to,
statements related to the anticipated timing of the submission of a
Biologics License Application; that there is a high unmet need in
aPAP for a pharmacotherapy; that the evidence now clearly
demonstrates molgramostim has the potential to be a safe and
efficacious treatment option for aPAP patients; statements
regarding the therapeutic benefits of molgramostim in aPAP and the
impact of molgramostim on quality of life for aPAP patients; that
the strong efficacy data and favorable benefit-risk profile
potentially position molgramostim to be the first and only approved
therapeutic for aPAP in the U.S. and Europe; and that Savara
anticipates submitting the full data from IMPALA-2 for presentation
at a scientific conference later this year. Savara may not actually
achieve any of the matters referred to in such forward-looking
statements, and you should not place undue reliance on these
forward-looking statements. These forward-looking statements are
based upon Savara’s current expectations and involve assumptions
that may never materialize or may prove to be incorrect. Actual
results and the timing of events could differ materially from those
anticipated in such forward-looking statements as a result of
various risks and uncertainties, which include, without limitation,
the risks that analysis of the full data set from the IMPALA-2
clinical trial could result in observations not seen in the top
line results; the risks associated with our ability to successfully
develop, obtain regulatory approval for and commercialize
molgramostim for aPAP; the risks and uncertainties relating to the
impact of widespread health concerns impacting healthcare providers
or patients and geopolitical conditions on our business and
operations, the ability to project future cash utilization and
reserves needed for contingent future liabilities and business
operations, the availability of sufficient resources for Savara’s
operations and to conduct or continue planned clinical development
programs, and the timing and ability of Savara to raise additional
capital as needed to fund continued operations. All forward-looking
statements are expressly qualified in their entirety by these
cautionary statements. For a detailed description of our risks and
uncertainties, you are encouraged to review our documents filed
with the SEC including our recent filings on Form 8-K, Form 10-K
and Form 10-Q. You are cautioned not to place undue reliance on
forward-looking statements, which speak only as of the date on
which they were made. Savara undertakes no obligation to update
such statements to reflect events that occur or circumstances that
exist after the date on which they were made, except as may be
required by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240626719994/en/
Savara Inc. IR & PR Anne Erickson
(anne.erickson@savarapharma.com) (512) 851-1366
Savara (NASDAQ:SVRA)
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