pSivida (PSDV) Reports Positive Iluvien FAME Phase III Results
pSivida Corp. (NASDAQ: PSDV) today reported top-line 24 month results from the Phase III FAME study of Iluvien for the treatment of Diabetic Macular Edema (DME) being conducted by pSivida's collaborative partner Alimera Sciences. The Company will host a conference call and webcast today at 4:30 pm Eastern Time (details follow below). More detailed information is available in the Company's Form 8-K filed today with the Securities & Exchange Commission.
The FAME study was designed as two Phase 3 pivotal clinical trials (Trial A and Trial B). 956 patients with DME were enrolled and randomized to receive either a high dose Iluvien (0.45 g/day), a low dose Iluvien (0.23 g/day) or a sham insertion. 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 Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at month 24 between the treatment and control groups.
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 were 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 approval with 24 month data.
Safety was assessed from all patients enrolled in the study. Intraocular pressure (IOP) increases to 30 millimeters of mercury (mmHg) or greater at any time point, a key adverse event studied in the trial, were seen in 21.6% of the high dose patients and 16.3% of the low dose patients. Over the 24 month period 5.1% of patients receiving the high dose and 2.1% of the patients receiving the low dose had received a trabeculectomy (filter surgery) to reduce their eye pressure.
Based on these and other data, Alimera plans to file for 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.
"We are very encouraged by these data and look forward to our collaborative partner Alimera filing the NDA for potentially the first ophthalmic drug therapy approved for DME," said Dr. Paul Ashton, President and CEO of pSivida. "These data further validate our drug delivery technology."
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 and imputes values 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 are described below:
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 patients randomized to control (p = 0.029 and 0.032, respectively). In Trial B of the ART analysis 30.8% of low dose patients and 31.3% of high 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, we believe 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.
"We look forward to the continued benefits of our agreement with Alimera, including a $25 million milestone payment that would be due on approval of Iluvien, profit participation on sales of Iluvien and payment of the $15 million conditional note from Alimera. If the note is not paid by April 2010, the annual interest rate increases to 20% (to be paid quarterly) and Alimera is to begin monthly principal payments of $500,000," Dr. Ashton continued.
The FAME study was designed as two Phase 3 pivotal clinical trials (Trial A and Trial B). 956 patients with DME were enrolled and randomized to receive either a high dose Iluvien (0.45 g/day), a low dose Iluvien (0.23 g/day) or a sham insertion. 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 Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at month 24 between the treatment and control groups.
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 were 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 approval with 24 month data.
Safety was assessed from all patients enrolled in the study. Intraocular pressure (IOP) increases to 30 millimeters of mercury (mmHg) or greater at any time point, a key adverse event studied in the trial, were seen in 21.6% of the high dose patients and 16.3% of the low dose patients. Over the 24 month period 5.1% of patients receiving the high dose and 2.1% of the patients receiving the low dose had received a trabeculectomy (filter surgery) to reduce their eye pressure.
Based on these and other data, Alimera plans to file for 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.
"We are very encouraged by these data and look forward to our collaborative partner Alimera filing the NDA for potentially the first ophthalmic drug therapy approved for DME," said Dr. Paul Ashton, President and CEO of pSivida. "These data further validate our drug delivery technology."
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 and imputes values 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 are described below:
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 patients randomized to control (p = 0.029 and 0.032, respectively). In Trial B of the ART analysis 30.8% of low dose patients and 31.3% of high 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, we believe 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.
"We look forward to the continued benefits of our agreement with Alimera, including a $25 million milestone payment that would be due on approval of Iluvien, profit participation on sales of Iluvien and payment of the $15 million conditional note from Alimera. If the note is not paid by April 2010, the annual interest rate increases to 20% (to be paid quarterly) and Alimera is to begin monthly principal payments of $500,000," Dr. Ashton continued.
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