Replies to post #112133 on Biotech Values

[DewDiligence]

Lucentis meets DME primary endpoint in first US phase-3 trial:

http://finance.yahoo.com/news/Lucentis-Phase-III-Study-bw-2840955060.html?x=0&.v=1

…a significantly higher percentage of patients receiving monthly Lucentis achieved an improvement in vision (BCVA) of at least 15 letters on the eye chart at 24 months, compared to those in a control group, who received a placebo (sham) injection…. Topline results from the RISE study will be presented at the 34th Annual Macula Society Meeting, on March 10, 2011 in Boca Raton, Florida.

24-month data is standard for the primary endpoint in DME, which is a slower-developing disease than AMD.

The commercial significance of this result is unclear insofar as Lucentis and Avastin are widely used for DME off-label in the US, the only country in which Lucentis is sold by Roche.

Lucentis is already approved for DME in the EU (#msg-58523789), where it is sold by NVS.

[DewDiligence]

Roche Reports Phase-3 Lucentis Data in DME

[These are the data from Roche’s first phase-3 DME study for the US market, called RISE; this study’s success was announced in February (#msg-59851581), but today is the first time the data have been disclosed. The only thing in the dataset that can be described as less than ideal is a slightly inverted dose response in the 0.3mg and 0.5mg arms; however, the trial was not powered to detect a difference between these arms.

Ever since Lucentis first showed efficacy in AMD many years ago, there has been little if any doubt that it would work in DME also. Lucentis is already approved for DME in the EU based on trials conducted by NVS (#msg-58523789). For FDA approval in DME, Roche is conducting a second phase-3 study called RIDE that is a clone of RISE and should be completed fairly soon (http://clinicaltrials.gov/ct2/show/NCT00473382 ).]

http://finance.yahoo.com/news/Phase-III-Study-of-Lucentis-bw-2630506671.html?x=0&.v=1

›Phase III Study of Lucentis Showed Rapid Vision Improvements Sustained for Two Years in Patients with Diabetic Macular Edema

Thursday March 10, 2011, 8:16 am EST

BOCA RATON, Fla.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that two-year results from a pivotal Phase III trial (RISE) showed patients with diabetic macular edema (DME) who received Lucentis® (ranibizumab injection) experienced rapid and sustained improvement in vision compared to those who received a placebo (sham) injection.

According to the data, there was:

• A significantly greater number of people able to read at least 15 additional letters on the eye chart compared to baseline after 24 months (primary endpoint),
• Significant improvement in average eye chart reading scores at 24 months,
• Significant improvement in average eye chart reading scores demonstrated as early as seven days,
• Significantly decreased retinal swelling.

“There are no FDA-approved medicines to treat DME and these new data add to evidence showing that Lucentis can help improve vision soon after initiation of treatment,” said Dennis M. Marcus, M.D., Southeast Retina Center in Augusta, Ga., who presented the data today. “In the case of the RISE study, the significant improvements on day seven were maintained for two years.”

DME is an eye condition characterized by swelling of the retina, which can occur in patients with type 1 or type 2 diabetes and can cause blurred vision, severe vision loss and blindness.1 DME is a leading cause of blindness among the working-age population in most developed countries. The safety results were consistent with previous experience and no new adverse events related to Lucentis were observed in the study.

The data from RISE, the first of two pivotal Phase III studies of Lucentis in DME, were presented today at the 34th Annual Macula Society Meeting in Boca Raton, Fla.

Study Results

At 24 months, 44.8 percent of patients (56/125) who received 0.3 mg Lucentis and 39.2 percent of patients (49/125) who received 0.5 mg Lucentis were able to read at least 15 more letters on the eye chart than they were at the start of the study, compared to 18.1 percent of patients (23/127) who received sham injections. The difference between each Lucentis dose group and the sham injection group was statistically significant.

In the study, changes in vision were measured by best-corrected visual acuity (BCVA), which is the best possible vision a person can achieve with corrective lenses, based on reading a standardized eye chart.

Key secondary endpoint data presented include:

• At 24 months, patients receiving 0.3 mg Lucentis had a mean gain in BCVA of 12.5 letters from baseline and patients receiving 0.5 mg Lucentis had a mean gain of 11.9 letters, compared with a mean gain of 2.6 letters for the sham injection group.

• As early as seven days (first post-baseline time point), patients receiving Lucentis demonstrated a statistically significant mean gain in BCVA: 5.4 letters for the 0.3 mg group and 4.6 letters for the 0.5 mg group, compared with 1.6 letters in the sham injection group. Improvements in BCVA in the Lucentis groups over the sham injection group were statistically significant at all time points between seven days and 24 months.

• The study also evaluated changes in retinal anatomy, including central foveal thickness. At 24 months, patients receiving 0.3 mg and 0.5 mg Lucentis showed a mean decrease of 250.6 microns and 253.1 microns from baseline, respectively, in central foveal thickness compared to a mean decrease of 133.6 microns in the sham injection group. Statistically significant improvements in the Lucentis groups over the sham injection group were noted at just one month after dosing (first tested time point) and were observed at all evaluated time points over the 24-month period.

Central foveal thickness was measured using an optical coherence tomography scan, which provides a cross-sectional image of the retina and can help identify and evaluate characteristics of the retina and macula, such as thickness and the presence or absence of swelling (edema).

Safety

An analysis of the 24-month data from the RISE study showed a safety profile consistent with previous Lucentis Phase III trials.

Common ocular adverse events that occurred more frequently in the Lucentis dosing groups than in the control group included conjunctival hemorrhage, eye pain, eye irritation, vitreous floaters, foreign body sensation in the eye and increased intraocular pressure. Serious ocular events occurring in the RISE study included one case of endophthalmitis, one retinal tear and two traumatic cataracts in the Lucentis groups.

Patients receiving Lucentis experienced fewer adverse events associated with diabetic retinopathy including retinal neovascularization (13.8 percent in the sham injection group, 0.8 percent in the 0.3 mg Lucentis dose group and 4.0 percent in the 0.5 mg Lucentis dose group), vitreous hemorrhage (13 percent in the sham injection group and 3.2 percent in each of the Lucentis dose groups) and retinal hemorrhage (20.3 percent in the sham injection group, 12.8 percent in the 0.3 mg Lucentis dose group and 12.7 percent in the 0.5 mg Lucentis dose group).

Preliminary analysis indicates no new findings related to non-ocular or systemic safety. The incidence of serious adverse events potentially related to systemic VEGF inhibition was 10.6 percent of patients in the sham injection group, 5.6 percent of patients in the 0.3 mg Lucentis dose group and 11.9 percent of patients in the 0.5 mg Lucentis dose group. Among non-ocular serious adverse events in the RISE study, 1.6 percent of patients in the sham injection group, 0.8 percent of patients in the 0.3 mg Lucentis dose group and 4.0 percent of patients in the 0.5 mg Lucentis dose group had strokes (cerebrovascular accidents). A total of 2.4 percent of patients in the sham injection group, 1.6 percent of patients in the 0.3 mg Lucentis dose group and 3.2 percent of patients in the 0.5 mg Lucentis dose group experienced a heart attack (myocardial infarction). A total of 0.8 percent of patients in the sham injection group, 2.4 percent of patients in the 0.3 mg Lucentis dose group and 4.0 percent of patients in the 0.5 mg Lucentis dose group died during the study.

About RISE

RISE is a multicenter, randomized, double-masked, sham injection-controlled, 36-month (sham injection-controlled for 24 months) Phase III study designed to assess the efficacy and safety of Lucentis in 377 patients with DME. Patients were randomized to receive monthly injections of either 0.3 mg Lucentis (n=125), 0.5 mg Lucentis (n=125) or monthly sham injections (n=127). The RISE study was not designed to compare the two doses of Lucentis, but each dose against the control group.

Beginning at three months, macular laser rescue treatment was made available to all patients, if needed based on pre-specified criteria. After month 24, patients in the control group were eligible to receive monthly injections of 0.5 mg Lucentis and all patients will continue to be followed and dosed monthly for a total of 36 months. The study then continues in an open-label extension phase.

About DME

DME is swelling of the retina that occurs in people with diabetes, who suffer from a complication called diabetic retinopathy. Diabetic retinopathy is the most common diabetic eye disease and is characterized by damage to the blood vessels of the retina, the nerve layer at the back of the eye. In DME, the damaged blood vessels leak fluid into the central portion of the retina, called the macula, causing it to swell. The macula is the part of the eye responsible for sharp central vision.1 The fovea is at the center of the macula. Approximately 26 million people in the United States (U.S.) have diabetes and 1.9 million new cases are diagnosed in people aged 20 and older each year.3 Up to 10 percent of all people with diabetes will develop DME during their lifetime and up to 75,000 new cases of DME are estimated to develop each year. The current standard of care for DME is laser surgery that helps seal the leaky blood vessels to slow the leakage of fluid and reduce the amount of fluid in the retina.‹