- Randomized, double-blind, placebo-controlled study did
not meet the primary endpoint: number of Respiratory Failure-Free
Days (RFDs) from randomization through Day 28 in the
intent-to-treat (ITT) population
- Nezulcitinib demonstrated a favorable trend in improvement
when compared to placebo for 28-day all-cause mortality rate
(p=0.08)
- In a post-hoc analysis, there was an improvement in
mortality (p=0.009) and time to recovery (p=0.02) in patients
treated with nezulcitinib who had baseline C-reactive protein (CRP)
levels <150 mg/L
- Nezulcitinib was well-tolerated when administered
once-daily for up to seven days
DUBLIN and SOUTH SAN FRANCISCO, Calif., June 21, 2021
/PRNewswire/ -- Theravance Biopharma, Inc. ("Theravance Biopharma"
or the "Company") (NASDAQ: TBPH), a diversified biopharmaceutical
company primarily focused on the discovery, development, and
commercialization of organ-selective medicines, today announced
top-line results from its Phase 2 study of 3 mg once-daily
nezulcitinib compared to placebo, each in combination with standard
of care. Nezulcitinib is an investigational, inhaled,
lung-selective, pan-Janus kinase (JAK) inhibitor in development for
hospitalized patients with confirmed COVID-19 associated acute lung
injury and impaired oxygenation.
"Since learning of the extensive respiratory complications in
severe COVID-19, we have worked to advance the science behind
inhaled lung-selective JAK inhibitors in critical diseases like
COVID-19," said Rick E Winningham, Chief Executive Officer,
Theravance Biopharma. "Even though this Phase 2 study,
enrolling more than 200 patients, did not meet the primary
endpoint, we are encouraged by the trend in the pre-specified
analysis of the 28-day mortality rate in the intent-to-treat
population. We are grateful to the patients and their families, our
research partners, the clinical investigators, and our team at
Theravance Biopharma for their important contributions."
"This is the first investigation of an inhaled JAK inhibitor
in COVID-19 patients. The classification of a COVID-ALI endotype
using a blood biomarker, such as C-reactive protein, may advance
the understanding and stratification of a subpopulation of patients
with immune characteristics that best responds to a
targeted-therapeutic such as nezulcitinib," said John Belperio, MD, professor of medicine in the
pulmonary and critical care department at the David Geffen School
of Medicine at UCLA and trial
investigator.
The study was a 1:1 randomized, double-blind,
placebo-controlled, multi-center Phase 2 trial for the treatment of
hospitalized COVID-19 patients (n=210) with impaired oxygenation
(NCT04402866). Key endpoints were measured through Day 28. Standard
of care in the study included approximately 99% receiving steroids
(91% received dexamethasone).
Key Study Findings
- Outcomes:
-
- Primary: No statistically significant difference in RFDs from
randomization through Day 28 between nezulcitinib and placebo in
ITT (median: 21 vs. 21 days; p=0.61).
- Secondary: No difference in change from baseline at Day 7 in
SaO2/FiO2 ratio, proportion of patients in
each category of the 8-point Clinical Status scale, and proportion
of patients alive and respiratory failure-free at Day 28.
- Nezulcitinib demonstrated a favorable trend in improvement when
compared to placebo for 28-day all-cause mortality (total number of
deaths: 6 vs. 13, HR: 0.42, p=0.08) and time to recovery (median:
10 vs. 11 days, HR: 1.27, p=0.12).
- In a post-hoc analysis of patients with baseline CRP
(n=201):
-
- In patients with CRP <150 mg/L (n=171), there was an
improvement in those treated with nezulcitinib when compared to
placebo in:
-
- 28-day all-cause mortality (total number of deaths: 1 vs 9, HR:
0.097, p=0.009).
- time to recovery (median: 10 vs. 11 days, HR: 1.48,
p=0.02).
- In patients with CRP >150 mg/L (n=30), there was no
difference in time to recovery or 28-day all-cause mortality
between those treated with nezulcitinib or placebo.
- Safety:
-
- Nezulcitinib was well-tolerated; adverse events and serious
adverse events occurred in 34.0% and 9.7% of patients treated with
nezulcitinib, and 41.2% and 15.7% of patients treated with placebo,
respectively.
- Adverse events of liver abnormalities or disease occurred in
9.7% and 7.8% of patients treated with nezulcitinib and placebo,
respectively.
- Serious infections and venous thromboembolism occurred in 1.0%
and none of the patients treated with nezulcitinib, and 2.0% and
4.9% in patients treated with placebo, respectively.
- Plasma exposure of nezulcitinib was low and consistent with
expectations for a lung-selective medicine.
The Company will share these results with FDA and other
regulatory agencies to seek input on protocols to further study
nezulcitinib in acute hyperinflammation in the lung. A more
detailed analysis of the data, including further pharmacokinetic
and biomarker results, will be available in the future.
Conference Call and Live Webcast Today at 8 am ET
Theravance Biopharma will hold a conference call and live
webcast accompanied by slides today at 8 am
ET / 5 am PT / 1 pm IST. To participate, please dial (855)
296-9648 from the U.S. or (920) 663-6266 for international callers,
using the confirmation code 6984147. Those interested in listening
to the conference call live via the internet may do so by visiting
Theravance.com, under the Investors section, Events and
Presentations.
A replay will be available on Theravance.com for 30 days through
July 21, 2021. An audio replay will
also be available through 11:00 am ET
on June 28, 2021, by dialing (855)
859-2056 from the U.S., or (404) 537-3406 for international
callers, and then entering confirmation code 6984147.
About Nezulcitinib
Nezulcitinib, also known as TD-0903, is an investigational,
inhaled, lung-selective, pan-JAK inhibitor that was discovered and
developed at Theravance Biopharma. Nezulcitinib has been shown in
experimental murine models to have potent, broad inhibition of
JAK-STAT signaling in the airways following challenges with
multiple cytokines. The organ selectivity of nezulcitinib is
demonstrated preclinically via a high lung: plasma ratio and rapid
metabolic clearance resulting in low systemic exposure. As an
inhaled JAK inhibitor, nezulcitinib is expected to intervene
broadly to interrupt excessive immune activation in the airways.
Nezulcitinib, delivered via nebulization, may present a novel
therapeutic modality to address the cytokine release syndrome that
has been associated with acute lung injury, ventilator use, and
increased morbidity and mortality in COVID-19 patients.
The Company previously reported results from the initial
dose-finding portion of this Phase 2 study, in which nezulcitinib
was generally well-tolerated and showed numerical improvements in
clinical outcome, duration of hospital stay, and fewer deaths
compared to placebo. Results of this dose-finding portion of the
Phase 2 study informed a decision to progress the 3 mg dose into
the larger Phase 2 study reported herein. Read more about the
dose-finding portion of the Phase 2 study here.
Nezulcitinib may also provide a potential treatment for other
causes of acute hyperinflammation of the lung and the prevention or
delay of lung transplant rejection.
About Theravance Biopharma
Theravance Biopharma, Inc. is a diversified biopharmaceutical
company primarily focused on the discovery, development and
commercialization of organ-selective medicines. Its purpose is to
pioneer a new generation of small molecule drugs designed to better
meet patient needs. Its research is focused in the areas of
inflammation and immunology.
In pursuit of its purpose, Theravance Biopharma applies insights
and innovation at each stage of its business and utilizes its
internal capabilities and those of partners around the world. The
Company applies organ-selective expertise to target disease
biologically, to discover and develop medicines that may expand the
therapeutic index with the goal of maximizing efficacy and limiting
systemic side effects. These efforts leverage years of experience
in developing lung-selective medicines to treat respiratory
disease, including FDA-approved YUPELRI® (revefenacin)
inhalation solution indicated for the maintenance treatment of
patients with chronic obstructive pulmonary disease (COPD). Its
pipeline of internally discovered programs is targeted to address
significant patient needs.
Theravance Biopharma has an economic interest in potential
future payments from Glaxo Group Limited or one of its affiliates
(GSK) pursuant to its agreements with Innoviva, Inc. relating to
certain programs, including TRELEGY.
For more information, please visit www.theravance.com.
THERAVANCE BIOPHARMA®, THERAVANCE®, and the Cross/Star logo are
registered trademarks of the Theravance Biopharma group of
companies (in the U.S. and certain other countries).
YUPELRI® is a registered trademark of Mylan Specialty
L.P., a Viatris Company. Trademarks, trade names or service marks
of other companies appearing on this press release are the property
of their respective owners.
Forward-Looking Statements
This press release contains and the conference call will contain
certain "forward-looking" statements as that term is defined in the
Private Securities Litigation Reform Act of 1995 regarding, among
other things, statements relating to goals, plans, objectives,
expectations and future events. Theravance Biopharma intends such
forward-looking statements to be covered by the safe harbor
provisions for forward-looking statements contained in Section 21E
of the Securities Exchange Act of 1934 and the Private Securities
Litigation Reform Act of 1995. Examples of such statements include
statements relating to: the Company's goals, designs, strategies,
plans and objectives, the Company's regulatory strategies and
timing of clinical studies (including the data therefrom), the
potential characteristics, benefits and mechanisms of action of the
Company's product and product candidates, the potential that the
Company's research programs will progress product candidates into
the clinic, the Company's expectations for product candidates
through development, the Company's expectations regarding its
allocation of resources, potential regulatory approval and
commercialization (including their differentiation from other
products or potential products), product sales or profit share
revenue and the Company's expectations for its expenses, excluding
share-based compensation and other financial results. These
statements are based on the current estimates and assumptions of
the management of Theravance Biopharma as of the date of the press
release and the conference call and are subject to risks,
uncertainties, changes in circumstances, assumptions and other
factors that may cause the actual results of Theravance Biopharma
to be materially different from those reflected in the
forward-looking statements. Important factors that could cause
actual results to differ materially from those indicated by such
forward-looking statements include, among others, risks related to:
disagreements with Innoviva, Inc. and TRC LLC, the uncertainty of
arbitration and litigation and the possibility that the results of
these proceedings could be adverse to the Company, additional
future analysis of the data resulting from our clinical trial(s),
delays or difficulties in commencing, enrolling or completing
clinical studies, the potential that results from clinical or
non-clinical studies indicate the Company's compounds or product
candidates are unsafe or ineffective, risks that product candidates
do not obtain approval from regulatory authorities, the feasibility
of undertaking future clinical trials for our product candidates
based on policies and feedback from regulatory authorities,
dependence on third parties to conduct clinical studies, delays or
failure to achieve and maintain regulatory approvals for product
candidates, risks of collaborating with or relying on third parties
to discover, develop, manufacture and commercialize products, and
risks associated with establishing and maintaining sales, marketing
and distribution capabilities with appropriate technical expertise
and supporting infrastructure. In addition, while we expect the
effects of COVID-19 to continue to adversely impact our business
operations and financial results, the extent of the impact on our
ability to generate revenue from YUPELRI® (revefenacin), our
clinical development programs (including but not limited to our
later stage clinical programs for izencitinib and ampreloxetine),
and the value of and market for our ordinary shares, will depend on
future developments that are highly uncertain and cannot be
predicted with confidence at this time. These potential future
developments include, but are not limited to, the ultimate duration
of the COVID-19 pandemic, travel restrictions, quarantines, social
distancing and business closure requirements in the United States and in other countries,
other measures taken by us and those we work with to help protect
individuals from contracting COVID-19, and the effectiveness of
actions taken globally to contain and treat the disease, including
vaccine availability, distribution, acceptance and effectiveness.
Other risks affecting Theravance Biopharma are in the Company's
Form 10-Q filed with the SEC on May 6,
2021 and other periodic reports filed with the SEC. In
addition to the risks described above and in Theravance Biopharma's
filings with the SEC, other unknown or unpredictable factors also
could affect Theravance Biopharma's results. No forward-looking
statements can be guaranteed, and actual results may differ
materially from such statements. Given these uncertainties, you
should not place undue reliance on these forward-looking
statements. Theravance Biopharma assumes no obligation to update
its forward-looking statements on account of new information,
future events or otherwise, except as required by law.
Contact: Gail B. Cohen
Corporate Communications
917-214-6603
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