MannKind Corporation
(Nasdaq: MNKD) announced results from a Phase 1a clinical evaluation
of MKC253, a formulation of GLP-1 (glucagon-like peptide) on Technosphere
particles that is delivered using the Company's proprietary inhaler. The
study was designed as an open-label, dose escalation, controlled safety and
tolerability trial, involving 26 healthy, adult, male subjects. Each
subject was assigned to one of five dose levels of MKC253 inhalation
powder: 0.05 mg, 0.45 mg, 0.75 mg, 1.05 mg or 1.5 mg.
The primary objective of the trial was to evaluate the tolerability of
ascending doses of the investigational product as determined by the
incidence and severity of reported adverse events. Secondary endpoints
included pharmacokinetic parameters of plasma GLP-1 and pharmacodynamic
parameters of plasma insulin and glucose.
GLP-1 plasma concentrations peaked very quickly, with a mean Tmax
occurring less than 3 minutes after inhalation. In the group that received
1.5 mg of MKC253, the mean Cmax of total GLP-1 was 507 pmol/L, with active
GLP-1 reaching a Cmax of 310 pmol/L. At all dose levels, MKC253 was well
tolerated. Even in subjects that achieved plasma GLP-1 concentrations in
excess of 100 pmol/L, the nausea and vomiting characteristically associated
with such levels was not observed.
In these healthy subjects, GLP-1-induced insulin release occurred
within 6 minutes of inhalation of MKC253. The insulin response was
dose-dependent. The release of insulin from the pancreas was confirmed by
corresponding significant increases in the levels of C-peptide. In subjects
that received 1.5 mg of MKC253, blood glucose concentrations were observed
to decrease for a period of approximately 20 minutes after inhalation. All
subjects were fasted prior to the administration of MKC253.
A greater proportion of the GLP-1 inhaled as MKC253 remained intact
during the period following administration than has been described in the
literature following subcutaneous or intravenous injection of GLP-1. In
this study, doses of 1.05 mg and 1.5 mg of MKC253 produced a ratio of
active-to-total GLP- 1 of approximately 67% whereas ratios of 20 - 33% have
been reported following intravenous administration of GLP-1.
"Our hypothesis at present is that delivery of active GLP-1 to the
arterial circulation via the lung avoids much of the degradation by
dipeptidyl peptidase-4 that occurs prior to the compound reaching the
primary site of endocrine action. Thus, we may be able to achieve a
different response profile with pulmonary MCK253 than that seen with
subcutaneous or intravenous administration of GLP-1. Moreover, the
pulsatile administration of MKC253 achieved with our proprietary
Technosphere delivery technology appears to avoid the dose-limiting
vomiting characteristically associated with GLP-1 and replaces a
physiological response lost in patients with diabetes that cannot be
replicated by other forms of GLP-1," said Dr. Peter Richardson, Corporate
Vice President and Chief Scientific Officer. "As well, with pulsatile
delivery, we may potentially avoid unusual adverse effects such as the
acute pancreatitis that has been described with presently marketed GLP
analogues."
"We believe that MKC253 represents a novel approach to the use of GLP-1
as a prandial therapy for diabetes either alone, or in combination with
prandial insulin. In addition, if we are able to demonstrate the same
weight reduction or satiety effects seen with long-acting analogues of
native GLP, MKC253 may have therapeutic potential in obesity. At present,
this indication for GLP-1 is currently limited by the need to administer
peptide hormones by injection. The results of this trial, although
preliminary, indicate once again that utilizing the Technosphere platform
to deliver a metabolically important peptide in a manner that produces a
unique time-action profile can potentially transform the therapeutic
paradigm for a significant disease."
About MannKind Corporation
MannKind Corporation (Nasdaq: MNKD) focuses on the discovery,
development and commercialization of therapeutic products for patients with
diseases such as diabetes and cancer. Its lead product, the Technosphere(R)
Insulin System, is currently in phase 3 clinical trials in the United
States, Europe and Latin America to study its safety and efficacy in the
treatment of diabetes. For more information on MannKind Corporation and its
technology, visit mannkindcorp.
Forward-Looking Statements
This press release contains forward-looking statements, including
statements related to MKC253 and MannKind's Technosphere platform. Words
such as "believes", "anticipates", "plans", "expects", "intend", "will",
"goal", "potential" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based upon
MannKind's current expectations and involve risks and uncertainties. Actual
results and the timing of events could differ materially from those
anticipated in such forward-looking statements as a result of these risks
and uncertainties, which include, without limitation, risks related to the
progress, timing and results of clinical trials, difficulties or delays in
seeking or obtaining regulatory approval, MannKind's ability to enter into
any collaborations or strategic partnerships, MannKind's ability to raise
additional financing and other risks detailed in MannKind's filings with
the Securities and Exchange Commission, including the Annual Report on Form
10-K for the year ended December 31, 2006 and periodic reports on Form 10-Q
and Form 8-K. You are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date of this press
release. All forward-looking statements are qualified in their entirety by
this cautionary statement, and MannKind undertakes no obligation to revise
or update any forward-looking statements to reflect events or circumstances
after the date of this news release.
MannKind Corporation
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