Friday, September 17, 2010

Drug pipeline updates

See current drug roster at this link:

Dry Eye Clinical Trial Roster

Here's the current lineup (also posted in today's bulletin):

THESE FOUR appear to be further along than anything else:

Novagali's Cyclokat (0.1% cyclosporine). Completed Phase III and we're waiting for a results announcement.

EyeGate Pharma's EGP-437 entered Phase III trials in June.

Can-Fite Biopharma's CF101 was approved on Sept 5 to enter Phase III.

Ista's Remura (low dose bromfenac) entered Phase III in September.

THESE NEXT SIX (or so?) appear to be next in line...

but I honestly don't know which are hot to trot, which are dead in the water and which are somewhere in between. If you know, by all means tell me.

With Alcon's pipeline, I'm either going to get this completely wrong or partially right if I'm lucky, so here goes:

- Alcon reportedly has a cyclosporine drug in the works. I'm guessing this is any or all, probably all, of the drugs referred to in the past year or so as "Alcon X", "Alcon 38583" (which shows a Phase II on completed in March this year) and Zyclorin (acquired last March from Sirion where it was called ST-603 which has several completed trials on On the other hand, neither Alcon's pipeline page nor shows any current cyclosporine drug. But something's out there. You don't buy it for nuthin'.

- Alcon also has Cilomilast, "and" Alcon 43546, which are listed separately on their pipeline page but which are also probably synonymous.

Resolvyx's RX-10045 is, according to the developer's site, now expected to enter Phase III next year.

SARCODE's SAR1118... we're waiting on an announcement as to whether and when they're proceeding to Phase III.

Inspire's Azasite completed Phase II's for the bleph indication. Funny, I noticed Alcon is running a clinical comparing it to Tobradex for bleph. Waiting on Phase III news.

Lantibio's Lancovutide is in post Phase II limbo too.

AND THEN there's these six, which are, or are claimed to be, in progress:

Otsuka/Aculela's rebamipide is in Phase II.

Mass Eye & Ear's Il-1-RA is in Phase II.

Regenerx's RGN259 is supposedly in Phase II.

Allergan's Restasis X is supposedly in Phase II.

Allergan's androgen tears, (cough choke) is supposedly in Phase II.


Inspire's Prolacria is now on the market in Japan, but Inspire is no longer pursuing it for FDA approval.

Opko's Civamide seems to be gonzo.

Santen's Sirolimus (Perceiva) is no longer being pursued for dry eye.

Ista's ecabet sodium was shelved in favor of the low dose bromfenac.

Alacrity's ALTY-0501 seems to be gonzo.


Argentis' testosterone and progesterone drugs.

Mimetogan's mucin secretagogues.

Lux Biosciences voclosporin drugs.

Thursday, September 16, 2010

Abstract: Passive cigarette smoke & contact lens wear

Anybody that's ever walked into a smoky nightclub can predict the results of this study just fine thank you. Not that there are too many of those left in the western world, though, are there? I never thought I'd live to see the day smoking was banned anywhere in Greece and yet it has.

Passive cigarette smoke exposure and soft contact lens wear.
Optom Vis Sci. 2010 May;87(5):367-72.
Ward SK, Dogru M, Wakamatsu T, Ibrahim O, Matsumoto Y, Kojima T, Sato EA, Ogawa J, Schnider C, Negishi K, Tsubota K.
Johnson and Johnson, Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo, Japan.

PURPOSE: To prospectively investigate the effects of passive cigarette smoke exposure on the ocular surface and tear film in soft contact lens (SCL) wearers.

METHODS: Twelve right eyes of 12 SCL wearers without any ocular or systemic diseases and 10 right eyes of 10 subjects who never wore CLs were examined before and 2 h after 5 min of passive cigarette smoke exposure in a controlled smoke chamber. Tear evaporation rate measurement, tear film break-up time (TBUT) examination, ocular surface fluorescein, rose bengal stainings, and Schirmer I test were performed at each visit.

RESULTS: The mean tear evaporation rates, TBUTs, and vital staining scores were significantly worse in CL wearers compared with healthy control subjects. TBUTs showed significant worsening after passive smoke exposure in both groups. The mean tear evaporation rate and vital staining scores showed a significant increase with brief passive smoke exposure in subjects not wearing CLs but not in CL wearers.

CONCLUSION: Even brief passive exposure to cigarette smoke is associated with adverse effects on the ocular surface as evidenced by an increase in tear instability and damage to the ocular surface epithelia in SCL wearers and non-CL wearers.

New drug news: Ista's Remura (low dose bromfenac) now entering Phase III clinical

ISTA Pharmaceuticals Initiates Phase 3 Clinical Program for REMURA™ in Dry Eye Disease
Sept 16, 2010 - PR NewsWire

RVINE, Calif., Sept. 16 /PRNewswire/ -- ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA), today announced that it has initiated a Phase 3 clinical program of ISTA's proprietary formulation of REMURA™ (bromfenac ophthalmic solution for dry eye) for alleviating the signs and symptoms of dry eye disease. The Phase 3 efficacy studies are being conducted under a Special Protocol Assessment (SPA) agreed upon with the U.S. Food and Drug Administration (FDA).

"We are pleased by the initiation of our pivotal REMURA dry eye efficacy program. Further, reaching agreement with the FDA on the SPA for REMURA efficacy studies provides additional clarity regarding the path to approval, which will help us to bring a safe and effective treatment to patients suffering from dry eye," stated Vicente Anido, Jr., Ph.D., President and Chief Executive Officer of ISTA. "Dry eye is a large and growing market, with 2010 worldwide prescription sales expected to be about $600 million. Dry eye also is an underserved market, as patients suffering from chronic dry eye syndrome have few quality therapy options. We are very excited by the potential of REMURA as a new treatment modality for dry eye patients."

At this time, ISTA plans to assess the safety and efficacy of REMURA in alleviating the signs and symptoms of dry eye disease by conducting four randomized, double-masked, placebo-controlled Phase 3 studies. The recently initiated Phase 3 studies will evaluate the efficacy and safety of bromfenac in two simultaneous studies operating under a common protocol in approximately 1000 patients with mild or moderate dry eye disease. The multi-center trials will be conducted at more than 30 sites in the U.S. Two concentrations of bromfenac (both lower than the currently marketed Xibrom (bromfenac ophthalmic solution)® 0.09%), will be dosed in addition to placebo. Patients will be randomized at a ratio of 1:1:1 to receive either bromfenac or placebo in both eyes twice daily and will be evaluated over the course of 42 days. For both efficacy studies, the objective sign of conjunctival staining will be measured using the Lissamine Green test and subjective symptoms will be measured using the Ocular Surface Disease Index (OSDI). ISTA anticipates reporting results in the middle of 2011.

The two remaining Phase 3 safety studies are the subject of additional SPAs currently under review by the FDA. To meet FDA guidance on drugs for chronic dosing, the Company expects to conduct both a six-month and a twelve-month safety study. ISTA anticipates it will initiate one or both of these safety studies later this year, subject to reaching agreement with the FDA on the SPAs.

Tuesday, September 14, 2010

Abstract: On office air syndrome (mostly) again

Ocular discomfort by environmental and personal risk factors altering the precorneal tear film.
Toxicol Lett. 2010 Sep 9. [Epub ahead of print]
Wolkoff P.
National Research Centre for the Working Environment, Copenhagen Ø, Denmark.

Ocular discomfort (e.g. burning, dry and itching eyes) is among top 2 symptoms in office environments. The ophthalmological explanation is aqueous-deficient dry eye and evaporative dry eye and exposure to allergens, while indoor air pollutants causing chemesthesis generally is the rationale of the indoor environmental community. Review of salient environmental, occupational, and personal risk factors, that alter the precorneal tear film (PTF), reveals at least three mechanisms resulting in ocular discomfort. First, the PTF structure is altered by a physical process that increases the emission rate of aqua loss resulting in hyperosmolarity, gland dysfunctions, and associated discomfort. Second, the structural composition of the outermost lipid layer of the PTF is altered by aggressive aerosols and combustion products, both indoors and outdoors, that facilitate loss of aqua, and possibly chemesthesis. Third, strong sensory irritating pollutants cause chemesthesis by trigeminal stimulation. In general, organic and inorganic indoor air pollutant concentrations are too low causing chemesthesis, but the odor may cause reported discomfort. The total risk of ocular discomfort is exacerbated by physical alteration of the PTF by visual tasking and climate conditions (low humidity, high temperature, and draft); further, personal factors like age, gender and use of certain medication also influence the overall stability of the PTF.