SAN DIEGO, Nov. 3, 2016 /PRNewswire/ -- Mast Therapeutics,
Inc. (NYSE MKT: MSTX), today announced that the Journal of Clinical
Investigation (JCI) published positive interim results from an
ongoing 50-patient Phase 2 study of AIR001 in patients with
pulmonary hypertension (PH), including a cohort with PH associated
with heart failure with preserved ejection fraction
(PH-HFpEF). In the Phase 2 study, AIR001 significantly
lowered pulmonary, right atrial, and pulmonary capillary wedge
pressures, with a substantial increase in pulmonary artery
compliance, which was most pronounced in patients with
PH-HFpEF.
In the 36 patients studied to date, administration of nebulized
inhaled nitrite (AIR001) significantly decreased pulmonary, right
atrial, and pulmonary capillary wedge pressures, and was most
pronounced in patients with PH-HFpEF. AIR001 administration also
led to a substantial increase in pulmonary artery compliance, which
was most pronounced in patients with PH-HFpEF. AIR001 was generally
well-tolerated and no significant safety concerns were identified,
satisfying the primary safety outcome of the study. In addition,
there were no significant decreases in peripheral oxygen saturation
nor increases in methemoglobin levels above the stopping criteria
of 5%.
"The results observed to date are important as they demonstrate
that AIR001 can significantly lower right atrial pressures,
pulmonary artery pressures, and pulmonary artery occlusion
pressures, as well as improve pulmonary artery compliance," stated
Edwin L. Parsley, D.O, Chief Medical
Officer of Mast Therapeutics, Inc. "In the study, AIR001
administration appears to be safe in Groups 1-3 PH and may be
efficacious in Groups 2 and 3 PH with further study in non-Group 1
PH warranted."
"These data are consistent with results we saw in a separate
investigator-sponsored Phase 2 study of AIR001 in HFpEF earlier
this year and serve as a further step in validating AIR001 and
establishing its potential clinical utility in HFpEF," stated
Brian M. Culley, Chief Executive
Officer of Mast Therapeutics. "We look forward to advancing AIR001
in this area of high unmet medical need for which there is no
FDA-approved therapy available. In addition to full results from
this 50-patient study, the 100-patient 'INDIE-HFpEF' study of
AIR001 also is expected to complete enrollment and announce
top-line results next year. We believe these are important
value-creating studies which convincingly demonstrate the potential
for clinical utility of AIR001 in HFpEF and potentially other
settings."
Of the 36 patients enrolled, 10 were diagnosed with PH-HFpEF, 20
were diagnosed with World Health Organization (WHO) Group 1
pulmonary arterial hypertension (PAH) on background PAH specific
therapy, and 6 were diagnosed with WHO Group 3 PH. In the 10
patients enrolled with PH-HFpEF, AIR001 administration resulted in
significant overall decreases in right atrial pressure, pulmonary
capillary wedge pressure, right ventricular systolic and diastolic,
and pulmonary artery systolic, diastolic and mean pressures. Of
note, pulmonary capillary wedge pressure and mean pulmonary artery
pressure markedly decreased by 7.5 mm Hg (95%CI: -9.0, -6.0) and
7.9 mm Hg (95%CI: -9.4, -6.3), respectively (baseline median values
18 and 34 mm Hg, respectively). With significant lowering of all
pressures, there was no significant change in transpulmonary
gradient and a modest but significant increase in PVR. Pulmonary
artery compliance increased by 35% (+0.97 mL/mm Hg, 95%CI: +0.25,
+1.68; P = 0.008).
Further analysis of the dose effect of AIR001 found that most
hemodynamics were affected in a dose dependent manner with the
exception of pulmonary artery compliance. There was a significant
dose effect on right atrial pressure, mean pulmonary artery
pressure, and pulmonary capillary wedge pressure. Cardiac index
decreased in a dose-dependent manner. The increase in pulmonary
artery compliance was not dose related.
About the Phase 2 Study
This is an institution-sponsored, single-center, open label
Phase 2 study to evaluate the effect of AIR001 delivered in a dose
escalation manner on the change in cardiovascular hemodynamics in
subjects with PH who undergo standard right heart catheterization.
The study will enroll a total of approximately 50 subjects with PH.
Approximately 20 of the subjects will have a diagnosis of PH
associated with HFpEF (WHO Group 2 PH). Subjects receive a
first dose of 45 mg of AIR001 via nebulizer, with one subsequent
escalation dosage to 90 mg approximately 60 minutes after the first
dose, based on safety and tolerability. During the study,
right heart/pulmonary artery hemodynamics are measured
continuously, and cardiac output is measured at 15 minute
intervals, as well as noninvasive systemic blood pressure and pulse
oximetry monitoring. Changes in hemodynamics and calculated
pulmonary systemic vascular resistances, as well as pulmonary
artery compliance will be performed utilizing standard
formulas.
About AIR001
AIR001 is a sodium nitrite solution for intermittent inhalation
via nebulization. Nitrite is a direct vasodilator and can be
recycled in vivo to form nitric oxide (NO) independent of
the classical NO synthase (NOS) pathway. Nitrite mediated NO
formation has several beneficial effects, including dilation of
blood vessels and reduction of inflammation and undesirable cell
growth. Generation of NO from sodium nitrite is not dependent upon
endothelial function and is enhanced in the setting of tissue
hypoxia and acidosis, conditions in which NOS activity typically is
depressed. In early clinical studies, AIR001 demonstrated positive
hemodynamic effects with reductions observed in right atrial
pressure and pulmonary capillary wedge pressure, as well as
improvements in mean pulmonary artery pressures, cardiac output,
and exercise tolerance as measured by six-minute walk distance. In
a randomized, double-blind, placebo-controlled Phase 2a study of
AIR001 in patients with HFpEF (n=26), the AIR001 treatment group
showed a statistically significant decrease in pulmonary capillary
wedge pressure during exercise compared to the control group and
AIR001 was generally well-tolerated.
About Mast Therapeutics
Mast Therapeutics, Inc. is a publicly traded biopharmaceutical
company headquartered in San Diego,
California. The Company has two clinical-stage
investigational new drugs, AIR001 and vepoloxamer. AIR001, a
sodium nitrite solution for intermittent inhalation via
nebulization, is in Phase 2 clinical development for the treatment
of heart failure with preserved ejection fraction (HFpEF).
More information can be found on the Company's web site at
www.masttherapeutics.com. Mast Therapeutics™ and the
corporate logo are trademarks of Mast Therapeutics, Inc.
Forward Looking Statements
Mast Therapeutics 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. Examples
of forward-looking statements in this press release include
statements relating to AIR001's potential utility to treat HFpEF,
the timing of completion and results of ongoing clincial studies of
AIR001, and the Company's development plans for AIR001.
Forward-looking statements should not be read as guarantees of
future performance or results because they involve the Company's
beliefs and assumptions based on currently available information
and are subject to significant known and unknown risks and
uncertainties that may cause actual performance and results to
differ materially from expectations indicated by the
forward-looking statements. Some of the factors that could cause
actual performance or results to differ include, without
limitation: the Company's need for additional funding and the risk
that it may not be able to obtain sufficient additional funding as
needed; risks associated with the Company's ability to manage
operating expenses; uncertainty related to the Company's ability to
continue to operate as a going concern; risk that the Company may
not be able to continue to comply with the terms and conditions
under its debt facility, which could result in the Company being
required to repay its remaining outstanding debt obligation on an
accelerated basis and/or at a time that could be detrimental to the
Company's financial condition, operations and/or business strategy;
the impact of significant reductions in the Company's operations on
its ability to develop its product candidates or maintain
compliance with laws and regulations relating to public companies;
the Company's ability to maintain compliance with NYSE MKT
continued listing standards and policies and to maintain the
listing and trading of its common stock on a national securities
exchange; uncertainties inherent in the conduct of clinical studies
and the risk that the Company's product candidates may not
demonstrate adequate safety, efficacy or tolerability in one or
more clinical studies for approval by regulatory authorities; the
Company's lack of control over the ongoing, investigator-sponsored
Phase 2 clinical studies of AIR001, including whether any of the
studies will be completed on anticipated timelines, or at all; the
potential for the Company to sell or license part or all of its
assets; the potential for significant delays, reductions, or
discontinuation of current and/or planned development activities if
the Company is unable to raise sufficient additional capital as
needed; the Company's dependence on third parties to assist with
important aspects of development of the Company's product
candidates, including the conduct of its clinical studies, the
manufacture and supply of its clinical trial material, including
drug delivery devices, and the conduct of regulatory activities,
and the risk that such third parties may fail to perform as
expected leading to delays in product candidate development and
additional costs; the risk that the Company is not able to obtain
or maintain effective patent coverage or other market exclusivity
protections for its products, if approved, or that the use or
manufacture of the Company's products may infringe the proprietary
rights of others; and other risks and uncertainties more fully
described in the Company's press releases and its reports filed
with the Securities and Exchange Commission. The Company's public
filings with the Securities and Exchange Commission are available
at www.sec.gov.
You are cautioned not to place undue reliance on forward-looking
statements, which speak only as of the date when made. Mast
Therapeutics does not intend to revise or update any
forward-looking statement set forth in this press release to
reflect events or circumstances arising after the date hereof,
except as may be required by law.
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