In July 2010, I wrote a comprehensive report about Iluvien and its potential in the treatment of diabetic macula edema (DME) (Iluvien and the Future of Ophthalmic Drug Delivery Systems). It was anticipated at that time that the company would obtain marketing approval for its sustained release treatment of DME by the end of that year. However, as I wrote in early January, the company received a CRL (complete response letter) from the FDA instead, that requested additional information before approval could be granted. (Iluvien Update: FDA Marketing Approval Delayed).
Earlier this week, Alimera Sciences and pSivida Corporation jointly announced that one of the FAME Study investigators had presented on a subset of the FAME Study data at the ARVO Meeting in Fort Lauderdale, and that the company (Alimera) plans to submit this new subgroup data to the FDA in support of its New Drug Application. Iluvien is licensed by pSivida to Alimera Sciences, Inc.
Here are the details:
Alimera's New 36-Month Safety and Efficacy Results From the Phase 3 Fame Study of Iluvien in Patients With Diabetic Macular Edema Presented at the 2011 Arvo Annual Meeting
Alimera Plans to Submit This New Data to the FDA in Support of Its Pending New Drug Application
Alimera Sciences, Inc. announced that positive new data from the completed FAME Study of Iluvien were presented at the 2011 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. The new data showed that 33.6% of patients in Trial A (p<0.001) and 42.4% of patients in Trial B (p<0.001) were observed achieving best corrected visual acuity (BCVA) improvement of 15 letters or more from baseline at month 30 in the identifiable subgroup of patients diagnosed with diabetic macular edema (DME) for three years or more at baseline. The new data were presented by Dr. Andrew N. Antoszyk, one of the FAME investigators and a practicing retina specialist at Charlotte Eye, Ear, Nose and Throat Associates in Charlotte, N.C.
The new data, presented by Dr. Andrew N. Antoszyk, analyzed the subgroup of patients who had been diagnosed with DME for three or more years at entry of the FAME Study (which comprises over 50% of patients in the Study).
The FAME Study consisted of two three-year, Phase 3 pivotal clinical trials (Trial A and Trial B) to assess the safety and efficacy of Iluvien in the treatment of DME. The 956 patients in the trials were randomized to receive either high dose Iluvien, low dose Iluvien or control treatment. The primary endpoint for efficacy in the trials was the difference in the percentage of patients whose BCVA improved by 15 or more letters from baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at month 24 between the treatment and control groups.
As previously reported, the pre-specified primary endpoint for the FAME Study was met for the low dose Iluvien in both Trial A and Trial B. Based on these data, Alimera submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) on June 29, 2010 for approval of the low dose Iluvien. Therefore, only the low dose data is presented and discussed here.
In February 2011, Alimera presented positive results from the full patient population at month 36 of the FAME Study in Trial A (28.4%) and Trial B (29.0%) with demonstrated improvement in BCVA of 15 letters from baseline. Statistical significance was seen in both trials as late as month 33 with Trial A at 28.4% (p=0.042) and Trial B at 29.6% (p=0.046).
Dr. Antoszyk's ARVO presentation on May 3rd included additional data from a subgroup of study patients that was identifiable prior to administration of Iluvien. This subgroup reflected the duration of DME at baseline and across all patients randomized, with a median duration of DME at baseline of three years.
In the data reported for this subgroup at 36 months in Trial A, 31.8% of patients treated with Iluvien experienced an improvement in best corrected visual acuity (BCVA) of 15 or more letters from baseline compared with 13.6% of those in the control group (p=0.010), for a net benefit of Iluvien versus control of 18.2%. In Trial B, 36.4% of Iluvien patients in this subgroup experienced improvement of 15 or more letters compared to 13.2% of control patients (p= 0.004), for a net benefit of Iluvien versus control of 23.2%. On a combined basis for both Trials A and B, at three years the net benefit of Iluvien compared to control reported for patients in the subgroup was 20.6%, more than double that seen for the full patient population (9.8%).
In the subgroup, peak efficacy was seen at month 30, with 33.6% of Iluvien treated patients in Trial A gaining 15 or more letters in BCVA compared to 10.2 % of control (p < 0.001) and 42.4% of Iluvien treated patients in Trial B gaining 15 or more letters in BCVA Trial B compared to 11.3% of control (p< 0.001).
Consistent with the full patient population in the FAME Study, approximately 75% of the patients in this subgroup treated with Iluvien were reported to have received only one Iluvien insert over the 36 month study.
There was no statistically significant difference in BCVA improvement in the subgroup of patients with less than three years' duration of DME at entry compared to control.
"Throughout the FAME Study, Iluvien has shown significant potential for patients suffering with DME. This new data is particularly exciting with 34% of patients who've had DME for three years or more gaining three lines of vision after therapy," said Dr. Antoszyk. "If regulatory approval of Iluvien is obtained, we will be able to offer an additional option in the form of a long-term treatment to our patients who are dealing with this devastating disease."
Data for the subgroup was gathered from 536 patients who had been diagnosed with DME for three years or more and 416 patients who had been diagnosed with DME for less than three years. Alimera will provide these additional data in its response to the Complete Response Letter issued by the FDA in December 2010.
Safety was assessed among those patients within the subgroup who were treated with Iluvien in the study. Intraocular pressure (IOP) increases to 30 millimeters of mercury (mmHg) or greater at any time point were seen in 14.8% of these patients by month 36, compared to 18.3% in the full Iluvien treated patient population. By month 36, 5.3% of these patients had undergone an incisional surgical procedure to reduce elevated IOP, compared to 4.8% in the full patient population. The incidence of cataracts among patients with a natural lens in their eye at the start of the study was 86% at month 36, with 85% undergoing a cataract operation, compared to 80% and 74.9%, respectively, in the full patient population.
"We are pleased that this identifiable subgroup shows even greater benefit to risk than the full patient population through month 36 of the study, thereby further improving Iluvien's profile," said Dan Myers, Alimera's president and CEO. "This data spotlights the benefit that Iluvien, if approved, could bring to the patient population that retinal specialists are targeting for its use. We believe this data will be very valuable to the treatment of DME going forward."
Paul Ashton, president and chief executive officer of pSivida, said, "We are very pleased with the efficacy and safety results through month 36 in patients with chronic DME. This subgroup comprised a majority of patients in the FAME Study. We look forward to Alimera's filing of this data with the FDA in connection with the NDA for Iluvien."
About the FAME Study
Alimera conducted two 36-month, Phase 3 pivotal clinical trials (collectively known as the FAME Study) for Iluvien involving 956 patients in sites across the United States, Canada, Europe and India to assess the efficacy and safety of Iluvien with two doses of the corticosteroid fluocinolone acetonide (FAc), a high and low dose, for the treatment of DME. The primary efficacy endpoint for the FAME Study was the difference in the percentage of patients whose best corrected visual acuity improved by 15 or more letters from baseline on the ETDRS eye chart at month 24 between the treatment and control groups. The study concluded in September 2010 with the final patient visit at the three-year data point.
Following its NDA submission to the FDA, Alimera submitted a Marketing Authorization Application to the Medicines and Healthcare products Regulatory Agency in the United Kingdom. Applications have also been submitted to regulatory agencies in Austria, France, Germany, Italy, Portugal and Spain. Based upon the analysis of the FAME Study, all filings included the 24-month data. The FDA, in a December 2010 Complete Response Letter, requested further information including the month 36 data from the FAME Study.
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 people with diabetes studied were diagnosed with DME. As the population of people with diabetes increases, Alimera expects the annual incidence of diagnosed DME to increase, as well.
Earlier this week, Alimera Sciences and pSivida Corporation jointly announced that one of the FAME Study investigators had presented on a subset of the FAME Study data at the ARVO Meeting in Fort Lauderdale, and that the company (Alimera) plans to submit this new subgroup data to the FDA in support of its New Drug Application. Iluvien is licensed by pSivida to Alimera Sciences, Inc.
Here are the details:
Alimera's New 36-Month Safety and Efficacy Results From the Phase 3 Fame Study of Iluvien in Patients With Diabetic Macular Edema Presented at the 2011 Arvo Annual Meeting
Alimera Plans to Submit This New Data to the FDA in Support of Its Pending New Drug Application
Alimera Sciences, Inc. announced that positive new data from the completed FAME Study of Iluvien were presented at the 2011 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. The new data showed that 33.6% of patients in Trial A (p<0.001) and 42.4% of patients in Trial B (p<0.001) were observed achieving best corrected visual acuity (BCVA) improvement of 15 letters or more from baseline at month 30 in the identifiable subgroup of patients diagnosed with diabetic macular edema (DME) for three years or more at baseline. The new data were presented by Dr. Andrew N. Antoszyk, one of the FAME investigators and a practicing retina specialist at Charlotte Eye, Ear, Nose and Throat Associates in Charlotte, N.C.
The new data, presented by Dr. Andrew N. Antoszyk, analyzed the subgroup of patients who had been diagnosed with DME for three or more years at entry of the FAME Study (which comprises over 50% of patients in the Study).
The FAME Study consisted of two three-year, Phase 3 pivotal clinical trials (Trial A and Trial B) to assess the safety and efficacy of Iluvien in the treatment of DME. The 956 patients in the trials were randomized to receive either high dose Iluvien, low dose Iluvien or control treatment. The primary endpoint for efficacy in the trials was the difference in the percentage of patients whose BCVA improved by 15 or more letters from baseline on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at month 24 between the treatment and control groups.
As previously reported, the pre-specified primary endpoint for the FAME Study was met for the low dose Iluvien in both Trial A and Trial B. Based on these data, Alimera submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) on June 29, 2010 for approval of the low dose Iluvien. Therefore, only the low dose data is presented and discussed here.
In February 2011, Alimera presented positive results from the full patient population at month 36 of the FAME Study in Trial A (28.4%) and Trial B (29.0%) with demonstrated improvement in BCVA of 15 letters from baseline. Statistical significance was seen in both trials as late as month 33 with Trial A at 28.4% (p=0.042) and Trial B at 29.6% (p=0.046).
Dr. Antoszyk's ARVO presentation on May 3rd included additional data from a subgroup of study patients that was identifiable prior to administration of Iluvien. This subgroup reflected the duration of DME at baseline and across all patients randomized, with a median duration of DME at baseline of three years.
In the data reported for this subgroup at 36 months in Trial A, 31.8% of patients treated with Iluvien experienced an improvement in best corrected visual acuity (BCVA) of 15 or more letters from baseline compared with 13.6% of those in the control group (p=0.010), for a net benefit of Iluvien versus control of 18.2%. In Trial B, 36.4% of Iluvien patients in this subgroup experienced improvement of 15 or more letters compared to 13.2% of control patients (p= 0.004), for a net benefit of Iluvien versus control of 23.2%. On a combined basis for both Trials A and B, at three years the net benefit of Iluvien compared to control reported for patients in the subgroup was 20.6%, more than double that seen for the full patient population (9.8%).
In the subgroup, peak efficacy was seen at month 30, with 33.6% of Iluvien treated patients in Trial A gaining 15 or more letters in BCVA compared to 10.2 % of control (p < 0.001) and 42.4% of Iluvien treated patients in Trial B gaining 15 or more letters in BCVA Trial B compared to 11.3% of control (p< 0.001).
Consistent with the full patient population in the FAME Study, approximately 75% of the patients in this subgroup treated with Iluvien were reported to have received only one Iluvien insert over the 36 month study.
There was no statistically significant difference in BCVA improvement in the subgroup of patients with less than three years' duration of DME at entry compared to control.
"Throughout the FAME Study, Iluvien has shown significant potential for patients suffering with DME. This new data is particularly exciting with 34% of patients who've had DME for three years or more gaining three lines of vision after therapy," said Dr. Antoszyk. "If regulatory approval of Iluvien is obtained, we will be able to offer an additional option in the form of a long-term treatment to our patients who are dealing with this devastating disease."
Data for the subgroup was gathered from 536 patients who had been diagnosed with DME for three years or more and 416 patients who had been diagnosed with DME for less than three years. Alimera will provide these additional data in its response to the Complete Response Letter issued by the FDA in December 2010.
Safety was assessed among those patients within the subgroup who were treated with Iluvien in the study. Intraocular pressure (IOP) increases to 30 millimeters of mercury (mmHg) or greater at any time point were seen in 14.8% of these patients by month 36, compared to 18.3% in the full Iluvien treated patient population. By month 36, 5.3% of these patients had undergone an incisional surgical procedure to reduce elevated IOP, compared to 4.8% in the full patient population. The incidence of cataracts among patients with a natural lens in their eye at the start of the study was 86% at month 36, with 85% undergoing a cataract operation, compared to 80% and 74.9%, respectively, in the full patient population.
"We are pleased that this identifiable subgroup shows even greater benefit to risk than the full patient population through month 36 of the study, thereby further improving Iluvien's profile," said Dan Myers, Alimera's president and CEO. "This data spotlights the benefit that Iluvien, if approved, could bring to the patient population that retinal specialists are targeting for its use. We believe this data will be very valuable to the treatment of DME going forward."
Paul Ashton, president and chief executive officer of pSivida, said, "We are very pleased with the efficacy and safety results through month 36 in patients with chronic DME. This subgroup comprised a majority of patients in the FAME Study. We look forward to Alimera's filing of this data with the FDA in connection with the NDA for Iluvien."
About the FAME Study
Alimera conducted two 36-month, Phase 3 pivotal clinical trials (collectively known as the FAME Study) for Iluvien involving 956 patients in sites across the United States, Canada, Europe and India to assess the efficacy and safety of Iluvien with two doses of the corticosteroid fluocinolone acetonide (FAc), a high and low dose, for the treatment of DME. The primary efficacy endpoint for the FAME Study was the difference in the percentage of patients whose best corrected visual acuity improved by 15 or more letters from baseline on the ETDRS eye chart at month 24 between the treatment and control groups. The study concluded in September 2010 with the final patient visit at the three-year data point.
Following its NDA submission to the FDA, Alimera submitted a Marketing Authorization Application to the Medicines and Healthcare products Regulatory Agency in the United Kingdom. Applications have also been submitted to regulatory agencies in Austria, France, Germany, Italy, Portugal and Spain. Based upon the analysis of the FAME Study, all filings included the 24-month data. The FDA, in a December 2010 Complete Response Letter, requested further information including the month 36 data from the FAME Study.
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 people with diabetes studied were diagnosed with DME. As the population of people with diabetes increases, Alimera expects the annual incidence of diagnosed DME to increase, as well.
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