MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA in Patients with Type 2 Diabetes

  MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA in
  Patients with Type 2 Diabetes

Business Wire

VALENCIA, Calif. -- August 14, 2013

MannKind Corporation (Nasdaq: MNKD) today announced positive preliminary
results from Study 175, a Phase 3 clinical study of AFREZZA^® (insulin human
[rDNA origin]) Inhalation Powder, an investigational, ultra rapid-acting
mealtime insulin therapy administered using MannKind’s next-generation (Gen2)
inhaler (also known as the Dreamboat™ inhaler), in patients with type 2
diabetes.

Highlights

AFREZZA combined with oral therapy, compared to oral therapy alone, showed:

  *Superior reductions in A1c levels;
  *Significantly more patients reached A1c target levels;
  *Reduced postprandial glucose excursions; and
  *No significant difference in the incidence of severe hypoglycemia.

“We are pleased that Study 175 met its primary endpoint of demonstrating that
AFREZZA, when added to a regimen of metformin with or without a second or
third oral medication, produced superior A1c reductions compared to oral
therapy alone,” stated Alfred Mann, Chairman and Chief Executive Officer of
MannKind Corporation. “In this study, significantly greater numbers of
patients in the AFREZZA group reached the American Diabetes Association goal
of A1c levels less than or equal to 7.0% and the American Association of
Clinical Endocrinologists goal of less than or equal to 6.5%. As well, the
AFREZZA group exhibited noticeably reduced postprandial glucose excursions. As
would be expected in a study that added insulin to an oral treatment regimen,
hypoglycemic events were more frequent in the AFREZZA group, but no AFREZZA
patient discontinued because of hypoglycemic adverse events. Based on the
results of this study, we believe that AFREZZA can be used to improve glycemic
control in insulin-naive type 2 diabetes patients that are not adequately
controlled on conventional oral medications – a potentially large and
underserved patient population.”

Study 175

Study 175 was a double-blind, placebo-controlled study involving 353 patients
with type 2 diabetes whose disease was inadequately controlled on metformin
with or without a second or third oral medication. Patients were studied at
sites in the United States, Russia, Ukraine and Brazil. After a six-week
run-in period during which all patients received dietary counseling and
initiated blood glucose monitoring while continuing their oral medications,
patients entered a 24-week treatment period in which they were randomized to
one of two groups where, in addition to their oral medication, they received
either:

  *AFREZZA Inhalation Powder, administered using the Gen2 inhaler (177
    patients); or
  *Technosphere Inhalation Powder (placebo), administered using the Gen2
    inhaler (176 patients).

The treatment period consisted of 12 weeks of prandial insulin titration
followed by 12 weeks of relatively stable dosing. Subjects could not adjust or
alter the doses of their oral medications during the study without discussion
between the principal investigator and the medical monitor. There was also a
safety follow-up visit four weeks after completion of the treatment period,
during which all subjects returned to oral therapy only.

The primary endpoint of the study was the mean change in A1c levels from
baseline to week 24 between the two groups. Over the 24-week treatment period,
mean A1c levels decreased by 0.82% in the AFREZZA group compared to a decrease
of 0.42% in the comparator oral-therapy group. The between-group difference in
change in mean A1c levels was statistically significant (p<0.0001), thereby
establishing the superiority of AFREZZA over the comparator oral-therapy
treatment.

Other Results

A significantly greater percentage of patients in the AFREZZA group reached
specified A1c target levels than in the comparator oral-therapy group. After
24 weeks of treatment, 37.7% of patients in the AFREZZA group achieved A1c
levels below 7.0% compared to only 19.0% of patients in the comparator
oral-therapy group (p=0.0005), and 15.9% of patients in the AFREZZA group
achieved A1c levels below 6.5% compared to only 4.2% of the patients receiving
only oral therapy (p=0.0021).

During the treatment period, postprandial glucose excursions were reduced in
the AFREZZA group compared to those in the comparator oral-therapy group. By
week 24, mean blood glucose levels did not exceed 170.2 mg/dL postprandially
in the AFREZZA group whereas mean blood glucose levels reached as high as
194.7 mg/dL postprandially in the comparator oral-therapy group.

Over the treatment period, mean fasting blood glucose levels decreased
moderately in the AFREZZA group by 11.2 mg/dL compared to a decrease of 3.8
mg/dL in the comparator oral-therapy group. This difference was not
statistically significant (p=0.1698).

Patients in the AFREZZA group gained an average of 0.49 kg over the treatment
period compared to an average loss of 1.13 kg by patients in the comparator
oral-therapy group (p<0.0001).

As expected, the incidence of mild and moderate hypoglycemia was higher in the
AFREZZA group (67.2% of patients) compared to the comparator oral-therapy
group (30.1% of patients; p<0.0001). However, there was not a significant
difference in the incidence of severe hypoglycemia, which was reported in nine
(5.1%) AFREZZA patients compared to three (1.7%) oral-therapy patients
(p=0.0943).

In general, treatment with AFREZZA was well-tolerated over 24 weeks by
subjects with type 2 diabetes. The incidence of serious adverse events was
lower in the AFREZZA group (2.8%) compared to the comparator oral-therapy
group (5.1%). The incidence of serious cardiovascular events was low overall
and balanced between the groups (AFREZZA: 2 events; oral therapy: 3 events).
Similarly, the incidence of adverse events resulting in discontinuation was
low overall and balanced between the treatment groups (AFREZZA: 4.0%; oral
therapy: 5.1%). The most common adverse event was cough, occurring with
comparable incidence in both the AFREZZA (23.7%) group and the oral therapy
(19.9%) group (who were also taking a placebo powder). Cough was predominantly
dry, intermittent, and usually occurred within 10 minutes of inhalation. The
incidence of cough in both treatment groups was highest during the first week
of the treatment period and diminished thereafter.

These preliminary results are subject to further analysis.

About AFREZZA^®

AFREZZA^® is a novel, ultra rapid-acting mealtime insulin therapy being
developed by MannKind Corporation for the treatment of adult patients with
type 1 or type 2 diabetes for the control of hyperglycemia. It is a
drug-device combination product, consisting of AFREZZA Inhalation Powder,
pre-metered into single-use cartridges, and a light, discreet and easy-to-use
inhaler. Administered at the start of a meal, AFREZZA dissolves immediately
upon inhalation and delivers insulin quickly to the bloodstream. Peak insulin
levels are achieved within 12 to 14 minutes of administration, effectively
mimicking the release of meal-time insulin observed in healthy individuals,
but which is absent in patients with diabetes.

About MannKind Corporation

MannKind Corporation (Nasdaq: MNKD) focuses on the discovery, development and
commercialization of therapeutic products for patients with diseases such as
diabetes. Its lead product candidate, AFREZZA^®, has completed Phase 3
clinical trials. MannKind maintains a website at www.mannkindcorp.com to which
MannKind regularly posts copies of its press releases as well as additional
information about MannKind. Interested persons can subscribe on the MannKind
website to e-mail alerts that are sent automatically when MannKind issues
press releases, files its reports with the Securities and Exchange Commission
or posts certain other information to the website.

Forward-Looking Statements

This press release contains forward-looking statements, including statements
related to the results of clinical studies, the potential use of AFREZZA to
improve glycemic control in insulin-naive type 2 diabetes patients who can no
longer be adequately controlled on conventional oral medications, and the
potential market opportunity for such use, that involve risks and
uncertainties. 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 the Company's current expectations. 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, difficulties or delays in obtaining regulatory
feedback or completing and analyzing the results of clinical studies,
completion of further statistical analysis of the results of Study 175,
whether the data from Study 175, as well as Study 171, the Phase 3 clinical
study of AFREZZA in type 1 diabetes patients, will satisfy all requirements of
the Food and Drug Administration and will be sufficient to support approval of
an amended new drug application for AFREZZA, the timing of regulatory review
and decisions, MannKind’s ability to manage its existing cash resources or
raise additional cash resources, stock price volatility 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, 2012
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 press release.

Contact:

MannKind Corporation
Matthew Pfeffer
Chief Financial Officer
661-775-5300
mpfeffer@mannkindcorp.com
 
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