Replies to post #1185 on Biotech Values

[DewDiligence]

Retaane update from Alcon quarterly release:

[Retaane is evidently only quarter behind Macugen in the timing of the NDA submission. The last sentence of the excerpt below may be a case of “methinks he doth protest too much.” Why would Alcon bother to mention patient retention, a.k.a. dropouts, if there were not a problem in this regard?]

http://biz.yahoo.com/bw/040420/206245_1.html

>>
The ongoing Phase III clinical trial for Retaane(TM) is on track for its 12 month readout of data in September, with likely publication of that data around the American Academy of Ophthalmology annual meeting in October. This would be followed by the filing of a New Drug Application in the fourth quarter of 2004. Patient retention has been consistent with statistical expectations.
<<

[DewDiligence]

Update on Alcon’s Retaane, including combo treatment:

[Some of the interim data presented here on the pivotal trial in wet AMD were disclosed last summer ( http://tinyurl.com/2bmlq ), but today’s PR has additional detail. The Retaane trials to test the progression of dry AMD to wet AMD, which were also disclosed previously ( http://tinyurl.com/22zp3 ) have now enrolled 5-10% of the total patients who will participate. These trials will run for at least five years after enrollment is complete.

What is totally new in today’s PR is the description of a physician-Initiated trial testing combination therapy with Retaane and the generic steroid, Triamcinolone.

Please refer to #msg-2955983 for the definitions of “improved vision,” “stable vision,” and “severe vision loss.”]

http://biz.yahoo.com/bw/040520/205795_1.html

>>
Alcon Presents RETAANE 15mg Depot Clinical Update at Association for Research and Vision in Ophthalmology Annual Meeting

FORT WORTH, Texas--(BUSINESS WIRE)--May 20, 2004--Alcon, Inc. (NYSE:ACL) reviewed data on the RETAANE® 15 mg (anecortave acetate for depot suspension) phase II/III study and updated information on two new phase III studies of anecortave acetate at the Association for Vision and Research in Ophthalmology (ARVO) annual meeting in Fort Lauderdale, Fla. In addition, a physician-initiated study of RETAANE® with triamcinolone was reviewed at the meeting. RETAANE® is being developed by Alcon, Inc. as a treatment for successfully preserving the vision of patients with all forms of wet age-related macular degeneration (AMD). Alcon expects to file a New Drug Application with the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2004. This filing will incorporate data from a current, multi-center, phase III clinical trial comparing RETAANE® with photodynamic therapy (PDT) in 530 patients with wet AMD. If approved, the company will begin marketing the product in the first half of 2005.

Phase II/III Clinical Update

Presentations at ARVO showed that RETAANE® was significantly better than placebo for preserving vision, preventing severe vision loss and inhibiting the growth of all lesion types in patients with wet AMD. At two years, 73 percent of patients treated with RETAANE® showed stable or improved vision, while only 47 percent of placebo-treated patients showed a similar vision outcome (p = 0.035). In addition, 94 percent of patients experienced no severe vision loss after two years treatment with RETAANE®. At twelve months, 79 percent of patients treated with RETAANE® had stable or improved vision, while only 53 percent of placebo-treated patients showed a similar vision outcome.

New Phase III Studies [in dry AMD]

Investigator Stephen Russell, M.D., of the University of Iowa Medical School, Carver School of Medicine, presented an update on Alcon's initiation of two new phase III studies being conducted in groups of patients with advanced dry AMD who are at risk of progressing to wet AMD. The studies will evaluate the safety and efficacy of treatment every six months with anecortave acetate for depot suspension versus a sham procedure. The sham procedure imitates the procedure used to give patients the investigational drug and is a regulatory requirement for keeping the study masked as to which patients receive the drug. Anecortave acetate is the first and only drug of its pharmacological class being investigated to treat this population of at-risk AMD patients. The FDA has granted Alcon "Fast Track" designation for the study of anecortave acetate for this indication because it represents a significant unmet medical need for a serious condition.

Dr. Russell presented the study methods for the new phase III trials. The protocol states that eligible patients must have, or previously have had, wet AMD in one eye, while the other eye has no evidence of exudative AMD or geographic atrophy. Patients enrolled in the trials will be randomized 1:1:1 to administrations every six months for four years of anecortave acetate 15 mg, anecortave acetate 30 mg, or to a sham procedure. To date, approximately 170 patients have been enrolled, out of the total of 2,500 patients for the two studies.

"In the study, anecortave acetate is being evaluated for treatment in arresting the progression from dry AMD to exudative AMD in at-risk patients using an important and clinically relevant measurement criteria, the incidence of 'sight-threatening' choroidal neovascularization, or CNV," said Dr. Russell. "For this study, sight-threatening CNV is defined as fluorescein angiographic evidence of new blood vessel growth under the retina within 2500 microns of the center of the macula."

Physician-Initiated Trial with RETAANE® and Triamcinolone [This is new info.]

In addition to the phase III information presented, investigator Jason S. Slakter, M.D., of the Manhattan Eye, Ear and Throat Hospital in New York, presented study methods and initial data for a physician-initiated trial evaluating the safety and efficacy of RETAANE® 15 mg (anecortave acetate for depot suspension) and triamcinolone acetate 4mg, or a combination of both, in patients with the wet form of AMD.(a) The protocol states that eligible patients must have either subfoveal occult CNV with demonstrated disease progression, or subfoveal minimally classic CNV. The first five patients in this study were treated with a combination of RETAANE® -- as the first line therapy -- and an intravitreal injection of triamcinolone acetate 4mg.

The results will serve as a preliminary safety assessment of the combination therapy. When the initial five patients complete the month 3 visit, another 60 patients will be enrolled in a masked study and assigned to receive either RETAANE® 15 mg (anecortave acetate for depot suspension) and a sham injection of triamcinolone acetate 4 mg, triamcinolone acetate 4mg and a sham administration of RETAANE®, or a true combination of the two drugs.

"Given the nature of these two drugs, it is possible that a combination of the agents may provide a synergistic effect, with the strong anti-permeability effect of the steroid combined with the anti-angiogenic effect of anecortave acetate," said Dr. Slakter.
<<

[DewDiligence]

“Rolling” Retaane NDA on target for 2Q05 launch:

[The clinical portion of the NDA will be filed in 4Q04, according to today’s PR, which is consistent with prior guidance from the company. Assuming the submission is made as planned, a six-month priority review would allow for an approval and launch in 2Q05. By the way, Retaane is yet another product being reviewed under the FDA’s CMA pilot program (not to be confused with an SPA).]

http://biz.yahoo.com/bw/040630/305154_1.html

>>
Alcon Updates Filing Status of RETAANE New Drug Application

Therapy is on Track for Launch in First Half of 2005

FORT WORTH, Texas--(BUSINESS WIRE)--June 30, 2004--Alcon, Inc. (NYSE:ACL - News) announced that it has filed the second portion of its "rolling" New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) for RETAANE® 15mg (anecortave acetate for depot suspension), an investigational treatment for preserving the vision of patients with all forms of wet age-related macular degeneration (AMD). The announcement was made today during a meeting of international retinal experts in Amsterdam, Holland.

RETAANE® depot is a fast track designated product that was also accepted into FDA's new Pilot 1 Continuous Marketing Application (CMA) program because of its potential as a treatment for a significant unmet medical need in patients with a serious condition. The "rolling" NDA permitted under this new FDA program allows designated NDAs to be submitted in specified reviewable units as each is completed, rather than as one package when the last unit is completed. The three main reviewable units are the Chemistry, Manufacturing and Controls (CMC) unit; the Pre-Clinical unit; and the Clinical unit. The fast-track designation provides a performance target for the FDA to complete its review of each unit within six months of its submission.

The FDA has completed its initial review of the RETAANE® depot CMC reviewable unit, which was filed in 2003. Furthermore, the pre-approval inspection of Alcon's manufacturing facility has been completed with no negative findings (no 483 observations). Alcon also submitted the Pre-Clinical unit for RETAANE® depot in March of this year, and has responded to all questions to date.

Alcon plans to complete the submission of the RETAANE® depot NDA with the filing of the Clinical unit in the fourth quarter of 2004. This unit will incorporate the twelve-month results from the on-going, multi-center, phase III clinical trial comparing RETAANE® depot with photodynamic therapy (PDT) in 530 patients with wet AMD, along with results from other clinical studies completed during the development program. If approved, consistent with the spirit of the CMA Pilot, Alcon is prepared to quickly make RETAANE® depot available for treating wet AMD.

"By piloting new review programs such as the Continuous Marketing Application program, the FDA is taking significant steps to ensure that safe and effective treatments that address significant unmet medical needs are efficiently made available to the American public," said Scott Krueger, Ph.D., Alcon's Vice President of Regulatory Affairs. "In anticipation of the upcoming twelve-month clinical safety and efficacy data from our ongoing Phase III study, we are looking forward to submitting for FDA review the final NDA unit for RETAANE® depot. Once we have filed this last unit, we believe the drug development program for RETAANE® depot will have generated a compelling database that supports its use as a treatment for wet AMD."
<<