Biotech Values

[DewDiligence]

One of PSDV’s two phase-3 trials in DME failed to hit its primary
endpoint, and the other trial may also have failed, depending on
the FDA’s interpretation. The PR headline touts “positive results,”
but we’ve all seen this game before. CC today at 4:30pm ET.

http://finance.yahoo.com/news/pSivida-Announces-Positive-bw-3158345775.html?x=0&.v=1

›pSivida Announces Positive Results from the Two Phase 3 FAME Trials of Iluvien® in Patients with Diabetic Macular Edema

More patients receiving either the High Dose or Low Dose Iluvien showed improvement in best corrected visual acuity of 15 or more letters at 2 years compared to those receiving sham treatment. This was statistically significant.

pSivida’s licensee, Alimera Sciences, plans to file New Drug Application (NDA) in the second quarter of 2010.

Wednesday December 23, 2009, 7:30 am

WATERTOWN, Mass.--(BUSINESS WIRE)--pSivida Corp. (NASDAQ: PSDV )(ASX:PVA)(FF:PV3), a drug delivery company with two of the only three ophthalmic sustained release delivery products approved by the FDA for treatment of back of the eye diseases, 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 µg/day), a low dose Iluvien (0.23 µg/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.

Based on Alimera’s analysis of the Full Analysis Set, as described by the International Conference on Harmonization (ICH) Guidance E9 and adopted by the FDA, the primary efficacy endpoint was met with statistical significance for both doses of Iluvien in each of Trial A and Trial B, as well as on a combined basis, as shown below:

Trial A Trial B Combined
Individual Percentage p-value Individual Percentage p-value Individual Percentage p-value

Control 14/95 14.7% -- 16/90 17.8% -- 30/185 16.2% --
Low Dose 51/190 26.8% 0.029 57/186 30.6% 0.030 108/376 28.7% 0.002
High Dose 51/196 26.0% 0.034 62/199 31.2% 0.027 113/395 28.6% 0.002

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.

More detailed analyses will be presented in February 2010 at the Angiogenesis, Exudation and Degeneration 2010 Meeting in Miami, Florida.

Conference Call Information

pSivida will host a conference call and live webcast to discuss the FAME Study results at 4:30 p.m. ET today, December 23, 2009. The conference call may be accessed by dialing [phone] from the U.S. and Canada, or [phone] from international locations, passcode 11287634. Listeners are encouraged to login at least 15 minutes prior to the start of the scheduled presentation to register, download and install any necessary audio software.

A replay of the call will be available approximately two hours following the end of the call through December 30, 2009. The replay may be accessed by dialing [phone] within the U.S. and Canada or [phone] from international locations, passcode 28531673.

The conference call will also be available via the internet at www.psivida.com and will be distributed through the Thomson StreetEvents Network. Individual investors can listen to the call via www.earnings.com and Institutional investors can access the call via www.streetevents.com. The call will be archived and accessible on the Web site for approximately 30 days.

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 956 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 (µg) per day dose), a second received a low dose of Iluvien (an approximate initial 0.23 micrograms (µg) per day dose) and the third group 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.

In addition to comparing the incidence of improvement in BCVA of 15 letters or greater from baseline between the treated and control arms, a numerical comparison of improvement of BCVA of 15 or more letters versus baseline was made between the month 24 and month 18 data, within each treatment arm. The results showed that the incidence of improvement at month 24 is numerically greater than that at month 18. Submission of the NDA will be based on the month 24 safety and efficacy data while the study will continue to month 36.

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 ten-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 diabetics increases, Alimera expects the annual incidence of diagnosed DME to increase.

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 for 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 pSivida Corp.

pSivida is a world leader in the development of tiny, sustained release, drug delivery products that are administered by implantation, injection or insertion. pSivida’s lead development product delivers fluocinolone acetonide (FA) for the treatment of diabetic macular edema (DME). This product candidate, formerly known as Medidur™ FA for DME, is licensed to Alimera, which is conducting fully-recruited Phase III clinical trials and intends to commercialize the product under the name Iluvien®. pSivida also has two products approved by the Food and Drug Administration (FDA): Retisert® for the treatment of posterior uveitis and Vitrasert® for the treatment of AIDS-related cytomegalovirus (CMV) retinitis. pSivida has licensed both of these products and the technologies underlying them to Bausch & Lomb Incorporated. pSivida has a worldwide collaborative research and license agreement with Pfizer Inc. under which Pfizer may develop additional ophthalmic products.

pSivida owns the rights to develop and commercialize a modified form of silicon known as BioSilicon™, which has potential therapeutic applications. The most advanced BioSilicon product candidate, BrachySil™, delivers a therapeutic P32, a radioactive form of phosphorus used to treat cancer, directly to solid tumors. pSivida conducted an initial safety clinical trial of BrachySil for the treatment of pancreatic cancer and in October 2009 completed a follow-on dose-ranging clinical trial.

pSivida’s intellectual property portfolio consists of 62 patent families, over 100 granted patents, including patents accepted for issuance, and over 200 patent applications. pSivida conducts its operations from Boston in the United States and Malvern in the United Kingdom.‹