MannKind Reports Positive Data from a Phase 3 Clinical Study of AFREZZA 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
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
- 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
About
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
MannKind Corporation
Matthew Pfeffer
Chief Financial Officer
661-775-5300
mpfeffer@mannkindcorp.com