LEXINGTON, Mass., July 17, 2018 /PRNewswire/ -- Pulmatrix, Inc.
(NASDAQ: PULM) announced today that all dosing and follow up visits
have been completed for Part 3 of the ongoing 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. Pulmazole was safe and well tolerated administered as a
single-dose of 20 mg inhaled itraconazole in asthmatic subjects.
Based on review of the top-line preliminary data, the study
successfully achieved all objectives. The company previously
reported positive top line data from Part 1 and 2 of the study in
normal healthy volunteers. With these encouraging Phase
1/1b results from Part 3 now also in
hand, Pulmatrix plans to initiate a Phase 2 trial in ABPA patients
in Q4 2018.
In the pharmacokinetic analysis of the data available, maximum
sputum itraconazole concentrations were approximately 50-fold
higher following inhalation dosing of 20 mg of Pulmazole compared
to oral Sporanox dosing of 200 mg. Additionally, high lung exposure
following inhalation of a single dose of 20 mg Pulmazole was
maintained over a 24-hour period, whereas sputum concentrations of
itraconazole decreased between 2 hours and 6 hours after a single
200 mg oral Sporanox dose. Following inhalation of 20 mg of
Pulmazole, total systemic exposure over 24 hours
(AUC0-24h) and maximum plasma concentration
(Cmax) were approximately 85-fold and 250-fold lower
compared to AUC0-24h and Cmax following 200
mg of oral Sporanox, respectively.
Dave Singh, MD, Professor of
Clinical Pharmacology and Respiratory Medicine at the University of
Manchester and principal
investigator on Part 3 of the study commented, "These data in
asthmatics are very promising regarding the future potential of
Pulmazole as a therapy for patients with ABPA, a disease with
significant unmet medical need. Demonstration of significantly
higher levels in the lung as well as significantly lower systemic
exposure following inhalation of Pulmazole suggests that Pulmazole
has the potential to dramatically improve upon the known safety and
efficacy of Sporanox."
The main objectives of the study in Part 3 were to evaluate the
safety, tolerability, and pharmacokinetics of Pulmazole
administered as a single-dose in mild-to-moderate asthmatics.
Subjects were administered 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 (including one
replacement subject) were dosed. The preliminary data reviewed
suggests that Pulmazole was safe and well tolerated. All study
drug-related adverse events (AEs) were characterized as mild, and
no moderate, severe or serious study drug-related AEs were
reported. The most common AEs in Part 3 following administration of
Pulmazole were mild and transient headache, and the infrequent
occurrence of a mild cough.
"These preliminary safety, tolerability and pharmacokinetic
results from Part 3 in subjects with asthma strongly corroborate
and further extend the positive findings we observed in normal
healthy volunteers," commented Jim
Roach, MD, Chief Medical Officer of Pulmatrix. "Notably,
itraconazole levels in the sputum of asthmatic subjects were much
higher following inhaled versus oral administration, despite
administering much lower doses of itraconazole via the inhaled
route. This further supports the potential of Pulmazole to improve
upon the efficacy observed with oral Sporanox in patients with
ABPA. We believe we have now generated the requisite data to
advance to initiation of a Phase 2 study in patients with asthma
and ABPA and are planning for study initiation in the fourth
quarter of this year. We look forward to submitting the Phase
1/1b study results in the next
several weeks for presentation at a major scientific conference
later this year."
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, inhaled anti-fungal
itraconazole for patients with ABPA, and PUR1800, a narrow spectrum
kinase inhibitor for patients with obstructive lung diseases
including asthma and chronic obstructive pulmonary disease
("COPD"). In addition, Pulmatrix has partnered with Vectura Group
plc to develop Pulmatrix's long-acting muscarinic antagonist drug
candidate, PUR0200, for COPD for the U.S. market. 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.