Alimera Announces Positive Results From the Two Phase 3 FAME Trials of Iluvien in Patients With Diabetic Macular Edema
For the patients treated with the low dose of Iluvien, 26.8% to 30.6% demonstrated improvement in best corrected visual acuity (BCVA) of 15 letters from baseline, and for patients receiving the high dose of Iluvien, 26.0% to 31.2% demonstrated improvement of 15 or more letters in BCVA from baseline, both at 2 years. Company plans to file a New Drug Application (NDA) in the second quarter of 2010. Alimera Sciences receives notices of exercise for an additional $10 Million in extended Series C financing.
ATLANTA, Dec. 23 /PRNewswire/ -- Alimera Sciences, Inc., a
privately held biopharmaceutical company that specializes in the
research, development and commercialization of prescription
ophthalmic pharmaceuticals, today reported top-line results from
the month 24 readout of the FAME Study.
The FAME Study consists of two Phase 3 pivotal clinical trials
(Trial A and Trial B) for the use of Iluvien in the treatment of
diabetic macular edema (DME). The primary efficacy endpoint for the
FAME Study is the difference in the percentage of patients whose
best corrected visual acuity (BCVA) improved by 15 or more letters
from baseline on the ETDRS eye chart at month 24 between the
treatment and control groups.
The month 24 analysis using the Full Analysis Set in Trial A
demonstrated statistical significance with 26.8% (p value 0.029) of
the low dose patients having an improvement in BCVA of 15 letters
or greater over baseline and 26.0% (p value of 0.034) of the high
dose patients having an improvement in BCVA of 15 letters or
greater from baseline. In Trial B, the month 24 data demonstrated
statistical significance with 30.6% (p value of 0.030) of the low
dose patients having an improvement in BCVA of 15 letters or
greater over baseline and 31.2% (p value of 0.027) of the high dose
patients having an improvement in BCVA of 15 letters or greater
from baseline.
The Full Analysis Set includes all 956 patients randomized into
the FAME Study, with data imputation employed using last
observation carried forward (LOCF) for data missing because of
patients who discontinued the trial or are unavailable for follow
up. (This data set is commonly referred to as the "intent to treat"
population.)
In addition, both the low and high dose Iluvien showed greater
numerical efficacy at month 24 than at month 18, a requirement for
submission with 24 month data in the United States.
Safety was assessed for all patients treated in the study.
Intraocular pressure (IOP) increases of 30 millimeters of mercury
(mmHg) or greater at any time point, a key adverse event studied in
the trial, were seen in 16.3% of the low dose patients and 21.6% of
the high dose patients. Over the 24 month period, 2.1% of patients
receiving the low dose and 5.1% of the patients receiving the high
dose had undergone a trabeculectomy (filtration procedure) to
reduce their eye pressure.
Based on these and other data, Alimera plans to seek approval of
the low dose of Iluvien for the treatment of DME in the second
quarter of 2010, followed by registration filings in various
European countries and Canada. Submission of the NDA will be based
on the month 24 safety and efficacy data while the FAME Study will
continue to month 36.
"I am very proud of the Alimera team for having completed trials
which we believe demonstrate efficacy at the month 24 clinical
readout and am confident that we will submit an NDA application for
Iluvien in 2010 for the treatment of DME. If approved, we believe
this would be the first drug approved for the treatment of this
condition," said Dan Myers, president and CEO of Alimera Sciences.
"Additionally, we appreciate the efforts of our clinical sites
around the world that have managed and continue to manage the
patients in the FAME Study."
In addition to the analysis described above, as prospectively
planned in the protocol, Alimera also conducted several other
analyses of the 24 month data. These included a) an All Randomized
and Treated (ART) analysis of the 24 month data that includes data
from all subjects randomized and treated with values imputed for
all missing data using the LOCF method, and b) a Modified ART
analysis that utilizes the ART population, but excludes data
collected subsequent to the use of treatments prohibited by
protocol (such as intravitreal injections of Avastin, Lucentis or
triamcinolone acetonide) with the last observation prior to
protocol violation imputed to month 24 using the LOCF method.
The results of these separate analyses were as follows: by the
ART analysis, in Trial A, 26.8% of low dose patients and 26.2% of
high dose patients gained 15 or more letters at 24 months compared
with 14.7% of control patients (p = 0.029 and 0.032, respectively).
In Trial B of the ART analysis, 31.3% of high dose and 30.8% of low
dose patients gained 15 or more letters compared with 17.8% of
control patients (p = 0.028 and 0.026 respectively). The results
for both doses in both trials were statistically significant. By
the Modified ART method, in Trial A 22.6% of patients in the low
dose and 24.1% of patients in the high dose gained 15 or more
letters compared with 12.6% of control patients (p = 0.057 and
0.026, respectively). Trial A was not statistically significant for
either dose. In Trial B by Modified ART, 29.7% of patients in the
low dose and 29.3% of patients in the high dose gained 15 or more
letters compared with 13.3% of control patients (p = 0.004 and
0.005, respectively). The results for both doses were statistically
significant.
The FAME study protocol provides that the primary assessment of
efficacy will be based on the Modified ART dataset and that the
other datasets will be considered secondary; the protocol did not
specify the Full Analysis Set as a dataset for analyzing the study.
However, consistent with the FDA-adopted International Conference
on Harmonization guidance, it is anticipated that the FDA will
consider the Full Analysis Set to be the most relevant population
for determining safety and efficacy in Trials A and B.
A more detailed analysis will be presented in February 2010 at
the Angiogenesis, Exudation and Degeneration 2010 Meeting in Miami,
Florida.
ALIMERA SCIENCES RECEIVES NOTICES OF EXERCISE FOR AN ADDITIONAL
$10 MILLION IN EXTENDED SERIES C FINANCING
On August 24, 2009, Alimera announced that it had closed an
extension of its Series C financing in which it issued shares of
its Series C preferred stock and warrants to purchase shares of its
Series C preferred stock. By their terms, the warrants were to be
exercised in full within 30 days of the delivery of top line data
from the Company's Phase III trials for Iluvien. Today, Alimera
announced that it had received written notice from its principal
warrant holders of their election to exercise the warrants. This
warrant exercise, which will result in $10 million in proceeds to
Alimera, will close in January 2010.
About the FAME Study
The Phase 3 FAME Study consists of two multi-center, randomized,
double-masked trials for Iluvien in sites across the United States,
Canada, Europe and India. The two trials have identical protocols
and enrolled 953 patients across 101 academic and private practice
centers. Patients in each trial were randomly assigned to one of
three groups in a 2:2:1 randomization, respectively. One group
received a high dose of Iluvien (an approximate initial 0.45
micrograms per day dose), a second received a low dose of Iluvien
(an approximate initial 0.23 micrograms per day dose) and the third
group (control) received sham. The sham included all the steps
involved in the insertion procedure with the exception that
patients in this group had a blunt inserter without a needle to
apply pressure to the anesthetized eye in order to simulate an
insertion. This procedure mimics an intravitreal insertion and
helps to maintain proper patient masking.
About DME
DME, the primary cause of vision loss associated with diabetic
retinopathy, is a disease affecting the macula, the part of the
retina responsible for central vision. When the blood vessel
leakage of diabetic retinopathy causes swelling in the macula, the
condition is called DME. The onset of DME is painless and may go
undetected by the patient until it manifests with the blurring of
central vision or acute vision loss. The severity of this blurring
may range from mild to profound loss of vision. The Wisconsin
Epidemiologic Study of Diabetic Retinopathy found that over a
10-year period approximately 19% of diabetics studied were
diagnosed with DME. Based on this study and the current U.S.
diabetic population, Alimera estimates that there will be an
incidence of approximately 340,000 cases of DME annually in the
United States. As the population of people with diabetes increases,
Alimera expects the annual incidence of diagnosed DME to increase
as well.
About Iluvien®
Iluvien is an investigative, extended release intravitreal
insert that Alimera is developing for the treatment of DME. Each
Iluvien insert is designed to provide a therapeutic effect of up to
36 months by delivering sustained sub-microgram levels of
fluocinolone acetonide (FA). Iluvien is inserted in the back of the
patient's eye to a position that takes advantage of the eye's
natural fluid dynamics. Iluvien is inserted with a device that
employs a 25-gauge needle, which allows for a self-sealing
wound.
About Alimera Sciences, Inc.
Alimera Sciences is a biopharmaceutical company that specializes
in the research, development and commercialization of prescription
ophthalmic pharmaceuticals. Presently the company is focused on
diseases affecting the back of the eye, or retina. Its most
advanced product candidate is Iluvien®, which is being
developed for the treatment of diabetic macular edema, or
DME.
Alimera is also pursuing the development, license and
acquisition of rights to compounds and technologies with the
potential to treat diseases of the eye that Alimera believes are
not well treated by current therapies. Alimera has entered into
agreements with Emory University, where by it acquired exclusive,
worldwide rights under patent applications covering two classes of
nicotinamide adenine dinucleotide phosphate reduced form (NADPH)
oxidase inhibitors. Alimera's initial focus is on the use of NADPH
oxidase inhibitors in the treatment of the dry form of age-related
macular degeneration (AMD), particularly the late stage of this
condition known as geographic atrophy. Alimera plans to evaluate
the use of NADPH oxidase inhibitors in the treatment of other
diseases of the eye, including the wet form of AMD and diabetic
retinopathy.
For more information on Alimera Sciences, visit
www.alimerasciences.com.
Source: Alimera Sciences, Inc.
CONTACT: Katie Brazel of Fleishman-Hillard,
+1-404-739-0150,
katie.brazel@fleishman.com,
for Alimera Sciences
Web Site: http://www.alimerasciences.com/
Posted: December 2009
