Replies to post #1037 on Biotech Values

[ello]

How About Genr and Alcon Partnering in AMD?

Alcon To Initiate New Anecortave Acetate Clinical Trials For Age-Related Macular Degeneration

FORT WORTH, Texas, Nov. 13 /PRNewswire-FirstCall/ -- Alcon, Inc. will initiate two new phase III studies of Retaane(TM) (anecortave acetate for depot suspension) for treatment of age-related macular degeneration (AMD) -- the most common cause of blindness in people over the age of 60. The new trials will evaluate the safety and efficacy of treatment every six months with the investigational drug Retaane(TM) Depot versus placebo in a group of patients with advanced dry (or non-exudative) AMD who are at risk of progressing to wet (or exudative) AMD. After completion of enrollment, the studies will occur over a period of four years and will include approximately 2,500 patients who will be enrolled at 100 sites worldwide. Enrollment is scheduled to begin in January 2004. Alcon stated that the U.S. Food and Drug Administration (FDA) has given "Fast Track" designation to the development of Anecortave Acetate for this indication, because it represents a significant unmet medical need for a serious condition.

"These new trials represent uncharted territory for AMD therapy," said Jason S. Slakter, MD, of the Manhattan Eye, Ear and Throat Hospital and Chairman of the Anecortave Acetate Clinical Study Group. "Though not as severe a disease as the wet form of AMD, dry AMD may progress into wet AMD and therefore lead to extensive vision loss. Development of a treatment for people with dry AMD who have been identified as having high risk of progressing to wet AMD could be a breakthrough for the disease."

What is AMD?

"Macular degeneration" describes several eye disorders characterized by damage to the macula -- the light-sensitive cells near the center of the retina at the back of the eye. The macula is responsible for our ability to see with enough detail to read, drive, watch television and perform other activities that require focused, straight-ahead vision. When the cells of the macula degenerate and malfunction, the result is an increasing loss of central vision. Today, AMD is the leading cause of blindness in industrialized nations, primarily because there is a lack of effective treatments for the disease.

Dry AMD accounts for up to 90 percent of all cases of AMD. It occurs when the light-sensitive cells in the macula slowly die, gradually blurring central vision in the affected eye. Dry AMD typically develops slowly. Vision loss may be mild at first, becoming more noticeable over time. There is no approved medical treatment for dry AMD, and though it usually does not result in severe loss of vision or blindness, people with the disease may have difficulty recognizing faces and need additional light for "close-up" tasks like reading. Over time, dry AMD can progress to the wet form of the disease.


Wet AMD results from the rapid growth of abnormal blood vessels -- called choroidal neovascular (CNV) lesions -- under and towards the center, or macula, of the retina, the light-sensitive tissue in the back of the eye. As the fragile new vessels grow and proliferate, they frequently leak blood and fluid that accumulates under and lifts the macula. The resulting vessel growth and fluid accumulation separates the retina from its anchoring tissue and causes rapid damage. Consequently, vision is distorted or destroyed. About 200,000 new cases of wet AMD are reported each year in the United States.

Method of Action

Anecortave Acetate belongs to a class of compounds known as angiostatic cortisenes. Anecortave Acetate works by slowing or stopping the growth of new blood vessels, which leads to less leakage and less retinal damage. Retaane(TM) 15 mg Depot is currently in clinical trials to evaluate its safety and efficacy in the treatment of the wet form of AMD. A recently completed two-year study in patients with wet AMD who received treatment with Retaane(TM) 15 mg Depot every six months showed inhibition of all aspects of CNV lesion growth.

Retaane(TM) 15 mg Depot is the only potential treatment for wet AMD that is administered onto the outer surface of the back of the eye using a specially designed curved, blunt-tipped cannula that does not pierce the eyeball. Unlike other investigational approaches to the treatment of AMD, the method of delivery for Retaane(TM) Depot -- called posterior juxtascleral depot or PJD -- avoids the risk of intraocular infection and retinal detachment, the most common side effects associated with injecting therapeutic agents directly into the eye. To date, over 700 patients have been treated with anecortave acetate using PJD with no serious treatment-related side effects.

"The safety of the drug combined with the safety of posterior juxtascleral depot administration and a dosing frequency of every six months make Retaane(TM) Depot very appropriate for chronic use," said Donald J. D'Amico, MD, a Retina Specialist at the Massachusetts Eye and Ear Infirmary and Chairman of the Independent Safety Committee for Anecortave Acetate. "Taken together, these are extremely important factors in the selection of a therapy for long-term studies such as these."

The FDA's fast track designation is intended to address reviewing an investigational therapy that could treat an unmet medical need for a serious or life-threatening condition. The benefits of fast track status include: the opportunity to schedule more frequent meetings with the FDA to receive feedback on development plans; the option to submit a New Drug Application (NDA) piece-by-piece instead of all at once; and the option of submitting substitute endpoints for the study evaluation purposes.

About Alcon

Alcon, Inc. is the world's leading eye care company. Alcon, which has been dedicated to the ophthalmic industry for over 50 years, develops, manufactures and markets pharmaceuticals, surgical equipment and devices, contact lens solutions and other vision care products that treat diseases, disorders and other conditions of the eye.

Web site: http://www.alconinc.com

[DewDiligence]

Typo correction to #1037:

The sentence that reads: “The implant is tiny and is capable of delving drug to the virtual chamber for at least six months and perhaps as long as a year.”

should be changed to: “The implant is tiny and is capable of delivering drug to the vitreal chamber for at least six months and perhaps as long as a year.”

LOL

[isolution]

Allergan,

Dew, you wrote:
Clearly, AGN has a pretty full development program in the area of retinal diseases.

I quite agree with you, but it is only since last october, Allergan have been focused so far on the anterior segment of the eye, I mean drops.
They've been collaborating with Oculex since may 2001 for the use of their biodegradable implant technology, eventhough Oculex have been testing only one drug so far, a steroid.
This implant, Surodex is marketed in Asia and Mexico since few years and is implanted in anterior chamber, on post surgery indication (a small market, easily solved by drops).
The major drawback of this implant technology (even if it is better than the non-biodegradable implant from CDS/Baush&Lomb) is that you don't control the dissolution rate as you should for steroids, it delivers continuously at the same rate, and for steroid it is preferable to have high dose at the beginning and a tapered treatment later.
The same implant placed in the posterior chamber, Posurdex has the same problem. They've focused the indication on persistent Macular edema. As a consequence, you develop intraocular pressure (risk of glaucoma) and cataract (induced by steroids).
Concerning AMD, Allergan seems to work on 2 fronts: they collaborating with Entremed to use Panzem with Oculex'technology and they screen protein kinase inhibitor since their agreement (retinal disease project) with Bardeen Sciences Company. So far, I haven't seen anything coming out of this research. Also, they are not the only company to check te use of PK inhibitors in AMD indication.

Collaboration with Genaera? not sure since they are tight with Entremed on that subject.

Implant the future of drug delivery in the eye? Not convinced if you consider the side-effects. On the uveitis front, implant will be indicated, I think on very few diseases, since you cannot control the pattern of delivery. I rather see a combination product as one molecule delivered locally at high dose for a short time and an implant with a very small dose for a long time. Confirmation to this is the Arvo abstracts where they show preclinical data on microdose implants...

I quite agree with you when you suggest that Allergan is a company to follow in retinal diseases, but, like B&L, I am not convinced with their strategy and that they will be the big players in the arena of AMD.

Anyway Dew, One again it is local drug delivery story (Alcon, Genentech, Novartis, Eyetech, B&L, Allergan, Genvec, Neurotech, Oxford Biomedica, Oxigene)
Strange, I don't see Genaera in the list?

Regards

[DewDiligence]

Allergan’s oral Tazarotene to go before advisory panel:

[The panel meeting for Tazoral applies to the psoriasis indication only, but Allergan plans to test the same drug as an oral treatment for wet AMD. Tazoral is a close cousin of Accutane, the acne med from Roche. Roche is so worried about the possibility of birth defects, a side effect of this class of retinoid drugs, that even male patients are required to sign a statement confirming that they are not pregnant!]

http://biz.yahoo.com/rb/040709/health_allergan_3.html

>>
Allergan Shares Fall Ahead of Meeting

WASHINGTON July 9 (Reuters) - Shares of Allergan (NYSE:AGN) fell nearly 4 percent on Friday ahead of a key meeting over whether the company's new oral psoriasis medicine should be approved by the government and how best to prevent birth defects from the drug.

While company studies have shown the drug, called Tazoral, can treat severe psoriasis with fewer side effects, it still presents the danger of irregular skulls, cleft palates and other problems in infants.

An advisory panel of outside medical experts will have to balance those concerns when they meet on Monday to discuss whether to recommend the U.S. Food and Drug Administration (FDA) approve the treatment for severe psoriasis.

The agency usually follows the recommendation of its advisory panels.

Like its cream and gel cousins, the capsule version of tazarotene is part of a class of vitamin A-derived drugs called retinoids known to cause birth defects. Studies have shown the oral dose can also cause vision problems, back pain and headaches.

In a report released on Friday on the FDA's Web site, www.fda.gov, agency staff said Tazoral was shown to work well.

David Maris, an analyst for Banc of America Securities, said the report was "not surprising," and he expected the panel review would be "favorable."

Shares of Allergan closed down $3.27, or 3.7 percent to $85.18 on Friday on the New York Stock Exchange. "Risk averse investors may wish to wait for the panel review," Maris said, adding the stock was "near our target price."

Allergan's topical versions are approved to treat acne, wrinkling and milder psoriasis. But a company-funded study earlier this year found the capsule was safer and brought more long-term relief for severe psoriasis' scaly bumps and thick, flaky skin.

But the FDA suggests restrictions for female patients taking retinoids. The panelists will also discuss what steps Allergan should take to provide pregnancy warning information to doctors and patients taking the drug.

Manufacturers of other retinoids, most notably Accutane maker Roche (ROG.VX), have struggled to balance treating women and preventing infant risk. Roche urges doctors who prescribe Accutane to require routine pregnancy tests and counsel female patients to use two methods of birth control.

Allergan spokeswoman Caroline Vanhove said the company would likely follow "a similar program."

FDA staff also wrote in the report that they were worried that doctors, who are familiar with topical tazarotene acne medications, would use the oral form instead.

Earlier plans to spend $80 million to $100 million to seek approval for the drug as a treatment for acne, which affects nearly 17 million Americans, are "on hold," Vanhove said.

Psoriasis is not as common as acne, but it affects about 6 million to 8 million Americans and can be difficult to treat. About 1.5 million people have severe psoriasis.

Tazarotene is not a blockbuster for Allergan, which ranks its dermatology line behind its eye care and Botox products. Last year, combined sales of Tarozac [sic] and Avage, topical versions of tazarotene, grew 29 percent to $80 million.
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