LEXINGTON, Mass., Nov. 21, 2018 /PRNewswire/ -- Pulmatrix,
Inc. (NASDAQ: PULM) announced the results of the completed
first-in-human study of Pulmazole (PUR1900) — an
inhaled iSPERSETM formulation of the anti-fungal drug
itraconazole for the treatment of allergic bronchopulmonary
aspergillosis (ABPA) in patients with asthma.
The company previously reported positive top line data from
Parts 1 and 2 of the study in normal healthy volunteers, and from
Part 3 in asthmatic subjects. With the final results now in
hand, which both extend and confirm the previously reported
positive top line data, Pulmatrix plans to initiate a Phase 2 trial
in asthmatic patients with ABPA patients in Q4 2018.
Pulmazole appeared to be safe and well tolerated in normal
healthy subjects in Parts 1 and 2 at doses up to 35 mg, the
maximal dose tested, over 14 days of administration. Single
doses of Pulmazole 20 mg and oral Sporanox 200 mg
appeared to be safe and well tolerated in asthmatic subjects.
The most common adverse event (AE) reported was mild cough during
dosing, which resolved spontaneously in seconds to minutes.
No subject experienced an AE leading to withdrawal.
Sustained low-level systemic exposure after single and multiple
doses over 24 hours post-dose is indicative of high and sustained
lung exposure and supports once daily dosing. Very low
systemic exposure for itraconazole was observed across all doses,
with 106- to 400-fold lower itraconazole exposure after 14 days of
10 to 35 mg Pulmazole compared to expected values following
administration of oral Sporanox® 200 mg twice
daily. In asthmatics, adjusted geometric mean
AUC0-t was 66-fold lower after a single 20 mg inhaled
Pulmazole dose compared to a single 200 mg oral
Sporanox® dose. Geometric mean sputum itraconazole
Cmax was ~70-fold higher following 20 mg inhaled
Pulmazole versus 200 mg oral Sporanox® (4530 ng/mL
compared to 65.4 ng/mL).
David Denning, MD, Professor of
Infectious Diseases in Global Health and the Director of the
National Aspergillosis Centre, Manchester, UK and co-chair of the Pulmazole
Clinical Advisory Board, commented that "Itraconazole's track
record of greater than twenty-five years of usage and demonstrated
patient benefits for allergic fungal disease tells its own
story. Direct delivery of itraconazole into the lungs to
increase exposure in the lung where the disease is manifest, while
minimizing systemic exposure and associated side effects clearly
offers the potential to improve upon both the efficacy and safety
observed with oral itraconazole."
Jim Roach, MD, Chief Medical
Officer of Pulmatrix remarked, "With the phase 1 study results now
firmly in hand, we remain very enthusiastic about the potential for
Pulmazole to address the significant limitations associated with
oral itraconazole, and more importantly, to address the significant
unmet medical need that patients with asthma and ABPA currently
face. We believe that these results strongly support the
further advancement of Pulmazole into Phase 2 and look forward to
getting our next study underway next month."
The Phase 1/1b study included 58
patients in a 3-part open-label study in healthy adults (Parts 1
and 2) and in adults with mild to moderate, stable asthma (Part 3).
The main objectives of Part 1 single ascending dose and Part 2
multiple ascending dose were to evaluate the safety, tolerability,
and pharmacokinetics (PK) of Pulmazole administered either as a
single-dose or multiple-doses administered daily over 14 days in
normal healthy volunteers. The main objective in Part 3 was to
evaluate the safety, tolerability, and pharmacokinetics (PK) of
Pulmazole administered as a single-dose in mild-to-moderate
asthmatics, and an additional exploratory objective in Part 3 was
to characterize the concentrations of itraconazole in induced
sputum following single doses of inhaled Pulmazole and oral
Sporanox® solution in subjects with mild to moderate stable
asthma.
The maximum dose of Pulmazole administered in this study was 35
mg itraconazole. A total of 23 subjects were dosed across 4 cohorts
(5 mg, 10 mg, 25 mg, and 35 mg itraconazole) in Part 1, and a total
of 18 subjects were dosed across 3 cohorts (10 mg, 20 mg, and 35 mg
itraconazole) in Part 2. In Part 3, subjects were
administered as either a single dose of oral itraconazole
(Sporanox; 200 mg itraconazole) or Pulmazole (20 mg itraconazole)
in a crossover study design, to compare relative levels of
itraconazole in both the blood and sputum after being administered
by either route. Part 3 of the study was planned to include
16 asthmatic subjects. A total of 17 asthmatic subjects were
dosed.
A copy of the poster presented at the American College of
Allergy, Asthma, and Immunology in Seattle, Washington on November 17, 2018 is available on the Pulmatrix
website.
About ABPA
ABPA is a disease that occurs most often
in patients with underlying asthma or cystic fibrosis, and it is
characterized by an exaggerated allergic hypersensitivity response
of the immune system to the fungus Aspergillus colonizing and
growing in the airways. Oral itraconazole (Sporanox®) is currently
used as an adjunctive treatment to corticosteroids in ABPA
patients. However, its use is limited by poor bioavailability,
variable pharmacokinetics, and toxicity concerns related primarily
to the risk of gastrointestinal and cardiac side effects, as well
as extensive drug-drug interactions. The Pulmatrix Pulmazole
program is the first inhaled dry powder version of itraconazole
known to the company to be advanced into clinical development, with
the goal of improving upon the known safety and efficacy profile
associated with oral Sporanox by delivering the drug directly to
the lung.
About
Pulmatrix
Pulmatrix is a clinical stage biopharmaceutical company developing
innovative inhaled therapies to address serious pulmonary disease
using its patented iSPERSE™ technology. The Company's proprietary
product pipeline is focused on advancing treatments for serious
lung diseases, including Pulmazole, an inhaled anti-fungal for
patients with allergic bronchopulmonary aspergillosis ("ABPA"), and
PUR1800, a narrow spectrum kinase inhibitor for patients with
obstructive lung diseases including asthma and chronic obstructive
pulmonary disease ("COPD"). Pulmatrix's product candidates are
based on iSPERSE™, its proprietary engineered dry powder delivery
platform, which seeks to improve therapeutic delivery to the lungs
by maximizing local concentrations and reducing systemic side
effects to improve patient outcomes.
FORWARD-LOOKING STATEMENTS
Certain statements in this
press release that are forward-looking and not statements of
historical fact are forward-looking statements within the meaning
of the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995. The Company cautions that such statements
involve risks and uncertainties that may materially affect the
Company's results of operations. Such forward-looking statements
are based on the beliefs of management as well as assumptions made
by and information currently available to management. Actual
results could differ materially from those contemplated by the
forward-looking statements as a result of certain factors,
including but not limited to the ability to establish that
potential products are efficacious or safe in preclinical or
clinical trials; the ability to establish or maintain
collaborations on the development of therapeutic candidates; the
ability to obtain appropriate or necessary governmental approvals
to market potential products; the ability to obtain future funding
for developmental products and working capital and to obtain such
funding on commercially reasonable terms; the Company's ability to
manufacture product candidates on a commercial scale or in
collaborations with third parties; changes in the size and nature
of competitors; the ability to retain key executives and
scientists; and the ability to secure and enforce legal rights
related to the Company's products, including patent protection. A
discussion of these and other factors, including risks and
uncertainties with respect to the Company, is set forth in the
Company's filings with the Securities and Exchange Commission,
including its annual report on Form 10-K filed by the Company with
the Securities and Exchange Commission on March 13, 2018, as may be supplemented or amended
by the Company's Quarterly Reports on Form 10-Q. The Company
disclaims any intention or obligation to revise any forward-looking
statements, whether as a result of new information, future events
or otherwise, except as required by
law.
Investor
Contact
|
|
Robert Clarke,
CEO
|
William Duke,
CFO
|
(781)
357-2333
|
(781)
357-2333
|
rclarke@pulmatrix.com
|
wduke@pulmatrix.com
|
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SOURCE Pulmatrix, Inc.