Friday, September 1, 2006

Drug Pipeline

What's in the Pipeline

On their way to pharmacies (sooner or later)?

ALLERGAN/OPTIF: According to the 8/4 quarterly investor conference call, this new artificial tear is due out this quarter. Click here for webcast & PDF transcript.

SINCLAIR PHARMA/SPHP700: Sinclair recently announced this was approved by the MHRA as Medical Device Class I (Sterile) and will be marketed as a prescription drug for the dry eye market. We're waiting for Sinclair to get back to us about the actual ingredients. From the limited information available it sounds like a glorified artificial tear, but maybe they will surprise us. Click here for a PDF copy of the full press release. Update 8/14: They are not releasing any more information about the mechanism of the drug and reportedly may not have it actually on the market for up to two years.

Teetering on the brink (of what, we don't know)

INSPIRE/"PROLACRIA" (DIQUAFOSOL TETRASODIUM): The most recent official news is as newsless as the last few rounds: "No substantive updates" was the characterization in the conference call on Aug 8th. Having twice fallen short of FDA blessings, hopefully by their next quarterly call we'll know whether we're looking at 'third time's a charm' or, um, 'three strikes and you're out biiiiiig bucks'. If the former, it sounds like they will go down the same path as Restasis with a co-promotion arrangement.

In Phase III Clinicals

OTSUKA-NOVARTIS/REBAMIPIDE: A study completed in 2005 was published this month in Cornea, which demostrated that it stimulates proliferation of conjunctival goblet cells in primary culture. Let's hope it works for humans and not just rats. Click here for abstract. Otherwise, no new news. Phase III clinical trials ongoing. This still seems to be the furthest along of anything in the current pipeline (unless Diquafosol/Prolacria surprises us) especially as androgen tears seem to have ground to a halt. Click here for initial screening checklist and list of study centers.

NOVAGALI/NOVA22007: (No updates this month) Cyclosporine emulsion. Recently started Phase III clinicals after obtaining new funding. Click here for most recent press release.

NASCENT/ iDESTRIN (NP50301): (No updates this month) Estrogen ester compound (topical eyedrop). Phase IIb clinical completed, now all we need is money to move forward. Latest report was in early January (click here for press release) stating good results from Phase IIb with "no drug related serious adverse effects". Click here for Nascent's page.

SENJU-ISTA/ECABET SODIUM: (No updates this month) Mucin secretagogue. Expecting to start Phase III trials in 2007, having reported positive results from Phase IIb studies in February 06. Ista claim that this is the first drug to show efficacy in clinicals against both signs and symptoms of dry eye. Click here for most recent press release and here for ISTA's main (albeit very outdated) page on this.

In Phase II clinicals

NOVARTIS / PIMECROLIMUS (AMS981): (No updates this month) Recruiting for Phase II clinicals. Click here for more info (or patients interested in signing up click here).

LANTIBIO/MOLI1901: (No updates this month)Cystic fibrosis drug being attempted as a dry eye treatment. Currently undergoing Phase II trials in the US following positive results in european Phase I studies. Click here for a, uh, colorful graphic about the mechanism of action.

On the horizon (maybe)

SENJU/LACRITIN: (No updates this month) It's very early stages yet but we've been keeping an eye on this for well over a year and think it's one of the most interesting and promising things coming down the pipeline. Some results of rabbit eye studies presented at ARVO recently. Click here for some updates & abstract from ARVO posted in Dry Eye Talk.

CAN-FITE/BIOPHARMA/CF-101: (No updates this month) CF101 is currently in clinical trials as a treatment for rheumatoid arthritis. The company has announced that it will shortly initiate another clinical study to test the drug's efficacy in treating dry eye symptoms. Click here for more.

OTHERA/OT-551: (No updates this month) This is in Phase II clinical for preventing cataracts in patients who have undergone vitrectomy. Othera has stated they expect to begin Phase II clinicals for two additional indications, AMD and dry eye syndrome, next year. Click here for more.

PAI-2: (No updates this month) Research being done at University of Pennsylvania and Temple University; data presented at ARVO recently. Not a whole lot of info but it sounds interesting. Click here for more.

Dead? In a coma? Dazed? Speak to me, baby

ALLERGAN/ANDROGEN TEARS: Frustration is mounting at the mixed signals about this. We heard that excellent data were presented at ARVO, and we heard that the study is progressing. On the other hand, from other sources we've heard that Allergan have all but given up on this. Indeed their total silence about androgen on their website and on their 2Q conference call on Aug. 4th are not promising. We'd like to link to something, but there doesn't seem to be anything to link to. If this project is killed, we darned well want to know why, because we know many patients have benefitted from this kind of therapy. (Anyone listening?) If the current incarnation is dead in the water, we will hope for a reincarnation.

Thursday, August 31, 2006

Journal Roundup

NEW! In brief
Patient-friendly highlights of recently published studies

I had to blast through this month's abstracts in a hurry but I must say I enjoyed it more than anytime in recent memory! It was relatively light on intense 16-syllable laboratory science and instead included a very welcome infusion of articles on interactions, drug side effects, environmental-related studies and epidemiology. This kind of thing is immensely helpful in raising awareness of the life-impact of dry eye - y'know, patients as people, not just pairs of crackled corneas to douse with drugs now and then.

Here are some examples of articles I enjoyed this month:

Ointment on the lid margins: A study in the American Journal of Ophthalmology studied benefits of basically lining the lid margins with ointment while at work in an attempt to counteract the problems posed for dry eyes by the office environment.
Glaucoma and dry eye: A study in Cornea looked at how many patients with dry eye (ocular surface disease) suffer from glaucoma compared with those who do not have dry eyes. This is an important area as it should encourage more attention by eye doctors to the issues posed by having to manage dry eye and glaucoma at the same time. For example, people with dry eyes may be more vulnerable to harmful effects from preservatives in glaucoma medications.
Rebamipide: The development of new dry eye drugs is excruciatingly slow, or at least seems so when you can't get enough relief from already available remedies. Those who have been following the progress of Rebamipide may be interested in this study in Cornea, which shows improvement to goblet cells, which are responsible for the mucin part of our tears and which for many of us are a key area of concern in anticipating new treatments. The peer review and publication cycle is slow - this report was submitted in early 2005 - but it will at least provide more information than has been available.
Allergy & asthma meds and dry eye: A study in Current Allergy & Asthma Reports discusses the need for increased awareness of dry eye as a side effect of systemic medications, specifically antihistamines. Bravo!!! We need more vigilance in the medical community about this - along with blood pressure medications, acne medications and many more.
"The modern office environment dessicates the eyes?" The title of this article in Indoor Air says it all! We liked this so much we wrote to congratulate the authors.
3-question dry eye survey: Although I think there are already some good dry eye surveys available that help quantify patient symptoms, which in turn helps patient-doctor communication, there is a need for something simpler that can be efficiently used for large-scale studies, and this one sounds like it may work. Now lets get on with the large-scale studies!


Study highlights
Acta Ophthalmologica Scandinavica

STARRY-EYED: The results in the abstract seem to get slightly lost amongst all the 'buts', but... I think they're saying that people with dry eyes have poorer contrast sensitivity and more disability glare than people with healthy eyes, but.... Contrast sensitivity and disability glare in patients with dry eye. Puell et al, 2006 Aug;84(4):527-31. Click here for abstract.

American Journal of Ophthalmology

MORE OF THE SAME (PRESUMABLY). And the more repetition in this area the better, say we. The incidence and risk factors for developing dry eye after myopic LASIK. Savini et al, 2006 Aug;142(2):355-6. Abstract not available online when we went to press.

GOOPING UP THOSE LIDS: This is an interesting one: Take an ointment and apply it all along the lid margin rather than in the eye. The claim of improved symptoms is easy to believe - we've known many patients who do this regularly. We've got our concerns about ointments in general though and we'd like to see more long-term studies of what they do to ocular surface wettability. Successful tear lipid layer treatment for refractory dry eye in office workers by low-dose lipid application on the full-length eyelid margin. Goto et al, Am J Ophthalmol. 2006 Aug;142(2):264-270.e1. Click here for abstract.

DOESN'T GET MUCH SIMPLER THAN THIS : A 3-question dry eye survey is apparently accurate enough for use in epidemiological studies. Now let's get cracking on those studies! Validation and repeatability of a short questionnaire for dry eye syndrome. Gulati et al, 2006 Jul;142(1):125-131. Click here for abstract.

Archivos de la Sociedad Espanola de Oftalmologia

INFOMERCIAL BREAK for Systane... at least that's what we assume this is (haven't read the full article as we don't have a subscription). [Reduction of corneal permeability in patients treated with HP-guar: a fluorophotometric study.] Cervan-Lopez et al, 2006 Jun;81(6):327-32. Click here for abstract.

Cornea

MORE GLAUCOMA WITH DRY EYE: Ha - we thought it was the other way around, since so many people on glaucoma meds seem to get ocular surface irritation from the preservatives. This is an interesting retrospective study at the University of Cincinnati. We couldn't agree more with the last sentence in the results stating that "This information warrants increased attention to treatment and management of OSD and concurrent glaucoma." Incidence and prevalence of glaucoma in severe ocular surface disease. Tsai et al, Cornea. 2006 Jun;25(5):530-2. Click here for abstract.

AND WHAT'S GOOD ENOUGH FOR RODENTS MUST BE GOOD ENOUGH FOR US: Or at least our goblet cells. This is a study on Rebamipide completed in 2005. Rebamipide is in Phase III clinicals at present and we are hoping they will get this one approved promptly. OPC-12759 increases proliferation of cultured rat conjunctival goblet cells. Rios et al, 2006 Jun;25(5):573-81. Click here for abstract.

Current Allergy and Asthma Reports

ABOUT THAT ANTIHISTAMINE, DOC: I was very happy to see this one, as a reminder that patients need to be made aware of the potential side effects of non-ocular drugs they are taking. Can't tell you how many times I've had site visitors who had no idea their allergy or blood pressure meds might be related to their dry eye woes. Ocular toxicity of systemic asthma and allergy treatments. L Bielory, 2006 Jul;6(4):299-305. Click here for abstract.

Graefe's Archive for Clinical and Experimental Ophthalmology

EPITHELIAL CELL DENSITIES AND SUCHLIKE: This study compares corneal thickness, epithelial cell density and other corneal properties in the central and peripheral cornea of 3 groups of patients (incl. aqueous deficient and some with lagophthalmos) versus controls. In vivo confocal laser scanning microscopy of the cornea in dry eye. Erdelyi et al, 2006 Jul 28; [Epub ahead of print]. Click here for abstract.

Indoor Air

AND ALL COMPUTER USERS SAID, AMEN: Well, perhaps the cynics amongst us muttered something more like "That'll be the day." Look at this: "The workplace, thermal conditions, and work schedule (including breaks) should be planned in such a way to help maintain a normal eye blink frequency to minimize alterations of the pre-corneal tear film." Yes, yes, yes! The modern office environment desiccates the eyes? Wolkoff et al, 2006 Aug;16(4):258-65. Click here for abstract.

Infection and Immunity

MORE DETECTIVE WORK: One of the latest in efforts to understand components of the tear film and where they do and don't reside, this discusses GP340. Nothing jumped off the page at me as hugely exciting but you never know when one of these might turn into a clue to an effective new treatment. Glycoprotein 340 in normal human ocular surface tissues and tear film. Jumblatt et al, 2006 Jul;74(7):4058-63. Click here for abstract.

Investigative Ophthalmology & Visual Science

ANOTHER ONE OF THOSE: Sigh, all the right names, again, and again I'd just like to see it in words of fewer than ten syllables because this kind of science is just way over my head without some attempt at translation into English. Will somebody somewhere develop a vision for making this stuff more accessible to the rest of us? Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Corrales et al, 2006 Aug;47(8):3293-302. Click here for abstract.

HOW TO TELL GOOD TEARS FROM BAD: Especially since you can't ask the rabbits (even New Zealand Whites - and by the by, I gotta love people who are precise enough to identify the make and model of the rabbits in their abstract). But returning to the point, there seem to be some type(s) of phospholipids present only in dry eye tears. Identification and comparison of the polar phospholipids in normal and dry eye rabbit tears by maldi-tof mass spectrometry. Ham et al, 2006 Aug;47(8):3330-8. Click here for abstract.

Journal of Biomedical Materials Research (Part B, Applied Biomaterials)

HMMM - DEFINITELY ONE TO WATCH: "As a therapeutic strategy, we are working to develop a bioengineered tear secretory system...." Tissue-engineered tear secretory system: Functional lacrimal gland acinar cells cultured on matrix protein-coated substrata. Selvam et al, 2006 Jul 18; [Epub ahead of print]. Click here for abstract.

Journal of Biomedical Optics

YES, THEY REALLY ARE DIFFERENT. It's hard to get excited about an abstract establishing that the tear film in dry eyes and lens wearers differs from controls - or about a last sentence stating that artificial tears apparently help. Interferometric measurements of dynamic changes of tear film. Szczesna et al, 2006 May-Jun;11(3):34028. Click here for abstract.

Journal of Cataract & Refractive Surgery

TOO OUTRAGED TO THINK UP A CATCHY BLURB: A study in this month's JCRS challenges the FDA's listing of auto-immune diseases as a contraindication to LASIK. Valid points are made that "not all auto-immune diseases are equal", and the authors openly acknowledge the limited scope of what they are attempting (establishing incidence of severe complications only - they did NOT review any data on visual outcomes or dry eye) but even as a preliminary step towards removing this contraindication this is of great concern to us. The overall gist and this section left me foaming at the mouth: "One limitation of our study is that we do not have data on the incidence or severity of dry eye or dry-eye complaints... LASIK is associated with dry eye signs and symptoms. The high incidence and variability of dry-eye symptoms after LASIK in normal eyes and the retrospective nature of our study would have made any conclusions about dry eye unreliable." Great. Just great. Let's keep the lawyers at bay by establishing that LASIK may be just tootin' fine for many auto-immune patients, on the basis that so many people get dry eye after LASIK anyway that we really don't have a clue if having RA, lupus or Sjogrens makes it worse. Laser in situ keratomileusis in patients with autoimmune diseases, Smith et al, JCRS 2006; 32:1292-1295. Click here for abstract.

Journal Francais d'Ophtalmologie

OBOY, A NEW DIAGNOSTIC TOY! (Uh, wassup with the pet name?) The Video Tearscope ("Vi-Te") sounds like a very interesting development in non-invasive tear film diagnostics. Hope to see more on this as the research progresses. The Video Tearscope: a new method for evaluating lacrimal film in vivo, Ounnoughene et al, J Fr Ophth 2006 May;29(5):476-84. Click here for abstract.

Journal of Rheumatology

ANOTHER MARKER FOR SJOGRENS? The cumulative numbers and 'respectivelys' in the abstract are a little dizzying but there are some interesting results here in identifying activation markers of Sjogrens Syndrome. Comparative analysis of autoantibodies against a-fodrin in serum, tear fluid, and saliva from patients with Sjogren's syndrome. Yavuz et al, 2006 Jul;33(7):1289-92. Click here for abstract.

Journal of Zhejiang University (Science, B)

YA THINK? Golly, I'm sure no one ever noticed THIS before: Steroids make dry eyes feel better pretty durned fast. Maybe in a few years someone will discover a connection between steroid use and IOP - if we're really lucky. A clinical study of the efficacy of topical corticosteroids on dry eye. Yang et al, 2006 Aug;7(8):675-8. Click here for abstract.

Klinika Oczna

YADA... ON SECOND THOUGHT, NADA of value added here. [The evaluation of tears secretion after refractive surgery] Mrukwa-Kominek et al, 2006;108(1-3):73-7. Click here for abstract (translated). Article in Polish.

Ophthalmologica

I COUNTED EVERYTHING EXCEPT THE NUMBERS: Gulp. Back to the drawing board, please. How can you possibly - or rather why on earth would you bother to - attempt to gauge the cost of treating dry eye syndrome while excluding the primary forms of both treatment (artificial tear supplementation) and care (self-care and optometrists)? Worse, how could you possibly come up with a set of criteria that would determine fewer than 0.1% of the population have dry eye, even if you were trying hard to get it wrong? Worst, when you know it's wrong and are happy to admit it, why bother publishing it? The annual cost of dry eye syndrome in France, Germany, Italy, Spain, Sweden and the United kingdom among patients managed by ophthalmologists. Clegg et al, 06 Aug;13(4):263-74. Click here for abstract.