Saturday, August 25, 2012

Rebamipide in Phase III clinical (again)

Pardon me for not getting excited yet (we've been here before with this drug... long time ago now) but Rebamipide is back in Phase III clinicals. At this point though - rather like Diquafosol - it's already approved on being marketed in Japan. It will be interesting to see whether it makes it through the FDA this time around.

Acucela and Otsuka Pharmaceutical Announce the Initiation of a Phase 3 Clinical Trial to Evaluate Rebamipide Ophthalmic Suspension in Patients with Dry Eye Syndrome

SEATTLE & TOKYO, Jul 19, 2012 (BUSINESS WIRE) -- --Drug Already Approved and Marketed for Dry Eye Syndrome in Japan as--Mucosta(R) Ophthalmic Suspension UD2% 
Acucela Inc., a clinical stage biotechnology company focused on developing new treatments for blinding eye diseases, and Otsuka Pharmaceutical Co., Ltd., today announced the initiation of a Phase 3 clinical trial to evaluate rebamipide ophthalmic suspension in patients with dry eye syndrome. Dry eye is a multifactorial disease of the tears and ocular surface, and one of the most common diseases treated by ophthalmologists in their daily practices. According to the 2011 Market Scope Dry Eye Report, 25 million Americans and 370 million patients worldwide suffer from dry eye. 
Rebamipide ophthalmic suspension is a novel compound discovered by Otsuka Pharmaceutical and has a new mechanism of action to increase the level of mucin in the tear film covering the conjunctiva and cornea. In January 2012, the drug was launched for the treatment of dry eye syndrome in Japan as Mucosta(R) ophthalmic suspension UD2%.Subjective symptoms of dry eye vary and can include dryness, foreign body sensation, itching, burning sensation, eye pain and photophobia. Advanced dry eye syndrome may lead to serious complications and ocular surface damage that can result in decreased vision. 
"Advancing rebamipide ophthalmic suspension into late-stage development is an exciting and important milestone for Acucela and for the patients who suffer from the debilitating effects of dry eye," said Ryo Kubota, MD, PhD, chairman, president, and chief executive officer, Acucela Inc. "Today's announcement is in line with our strategy to develop leading-edge therapies to help patients living with disabling eye diseases around the world. We are excited about the initiation of this important clinical study for rebamipide, as we continue to advance our pipeline of innovative ophthalmology treatments through the clinic." 
Dr. Taro Iwamoto, President and Representative Director, Otsuka Pharmaceutical Co., Ltd., stated, "Following the launch of the product in Japan, we are pleased to start Phase 3 clinical trials for rebamipide ophthalmic suspension in the U.S. We are partnering with Acucela, a company with a wealth of experience in the field of ophthalmology in North America. Otsuka expects our Japan- originated new innovation, designed to normalize the quality of tears, will be welcomed by many patients in the U.S. who are waiting for new treatments." 
About the Rebamipide Ophthalmic Suspension Phase 3 Clinical Study 
This Phase 3 clinical study will be conducted to determine the efficacy and safety of 2% rebamipide ophthalmic suspension in subjects with dry eye syndrome. It is a multi-center, randomized, placebo-controlled, double-masked, parallel-group study. Approximately 560 subjects are planned to be enrolled equally into the two treatment groups and the study is expected to be completed by the end of 2013. 
About the Otsuka Pharmaceutical/Acucela Rebamipide Ophthalmic Suspension Agreement 
Otsuka Pharmaceutical and Acucela entered into an agreement on September 4, 2008 to co-develop rebamipide ophthalmic suspension for the treatment of dry eye syndrome in the United States. In addition to co-developing rebamipide ophthalmic suspension with Otsuka Pharmaceutical, Acucela will spearhead the regulatory strategy to gain approval for the product in the United States.

Abstract: CPAP and ocular surface

It's about time we started seeing some studies on CPAP and dry eye! This is the second study published on the topic in the last couple of months, both originating in Turkey (different teams and facilities however; here's the first). The rest of you need to get on this :)

The effect of continuous positive airway pressure treatmentfor obstructive sleep apnea syndrome on the ocular surface.

To evaluate the effect of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea syndrome on the ocular surface.
This is a prospective, sectional cohort study of 80 eyes of 40 patients diagnosed with obstructive sleep apnea syndrome. Routine ophthalmologic examination and ocular surface evaluation, including biomicroscopy, Schirmer 1 testing, tear break-up time measurement, ocular surface staining, and conjunctival impression cytology, were performed in both of each patient's eyes before and 4 months after starting CPAP therapy.
After CPAP therapy, increases in squamous metaplasia (Nelson classification: t = 0.34, P = 0.014) and Schirmer 1 score (t = 3.20, P = 0.008), and decreases in tear break-up time (t = -1.38, P = 0.008) in the right eyes were statistically significant, as compared with the pretreatment values. Although these parameters changed in a similar fashion in the left eyes, differences between the pre-CPAP and post-CPAP values were not significant.
The findings indicate that CPAP therapy increased ocular irritation, tear evaporation, and squamous metaplasia in the conjunctiva of the patients' right and left eyes. Although the parameters measured were similar in both eyes before CPAP therapy, these parameters changed significantly after CPAP therapy only in the right eyes. The observed differences between the right and left eyes require further investigation to determine the possible effects of sleeping position, CPAP mask displacement, and the other factors involved.

Cornea. 2012 Jun;31(6):604-8.
Hayirci EYagci APalamar MBasoglu OKVeral A.
Departments of Ophthalmology, Faculty of Medicine, Ege University, Izmir, Turkey.

Artificial tear market to top $2billion?

Global Market for Artificial Tears to Exceed US$2.0 Billion by 2018, According to New Report by Global Industry Analysts, Inc.

San Jose, California (PRWEB) July 18, 2012
The global market for artificial tears is highly diversified and varies from country to country, primarily depending on aging populace, percentage of women in the overall population, prevalence of auto-immune diseases, pollution levels and increased usage of computers and TVs - all factors that play a vital role in the enhancing the incidence of the disease and consequently in driving sales of such products. Consumer demographic and economic status also play a major role in the choice of products as consumers with low income tend to prefer the cheaper priced artificial tears over other costly alternatives. Therefore most of regions in the developing world such as Asia-Pacific and Latin America are high potential markets for such products, where a wide range of artificial tears are available over-the-counter (OTC)...
...In terms of market potential, the Asian market is primed to grow at a robust CAGR of about 14% through 2018. Sales of OTC ophthalmic products are witnessing an aggressive increase in developing Asian market, with its huge population base, rising income levels and under-penetrated market potential, positioning the region as an attractive manufacturing hub.....

Abstract: Correlating signs & symptoms

This study doesn't appear to have been hugely informative BUT I love the concept of it... that there must be some associations we can learn from between symptoms and signs of dry eye... and I hope to see much more research like this.

The present study aimed at analyzing the relationship between several particular symptoms, risk factors or global questionnaire scores and some tear clinical signs in early dry eye patients.
A total of 77 volunteers were enrolled in the study without any prior classification, although patients with severe dry eye were excluded. Two questionnaires were used to assess ocular symptoms and risk factors, and clinical tear signs were evaluated with four tests (osmolarity, ferning, break-up time and the phenol red thread test). Multiple linear regression analysis was performed to determine the relative predictive value of each particular ocular symptom and risk factor, for each clinical sign. This analysis was repeated using symptoms and risk factors global scores.
The symptom "eyes stuck shut in the morning" was the only predictor variable for the sign "ferning crystallization" (R = 0.228, p < 0.05) and "dryness" for "break-up time" (R = -0.315, p < 0.01). "Burning sensation" and "computer use for more than 3 h" were predictor variables for "tear osmolarity" (R = 0.342, p < 0.01), while "itching" and "female gender" were found to predict the outcomes of the "phenol red thread test" (R = -0.462, p < 0.05). Global questionnaire scores were not found to predict any tear clinical sign.
The present findings support the informative value of exploring the associations between clinical signs, ocular symptoms and risk factors by following an item by item strategy rather than opting for global questionnaire scores.

Curr Eye Res. 2012 May;37(5):357-64.
Julio GLluch SCardona GFornieles AMerindano D.
Ocular Surface Research Group, Optics and Optometry Department, Universitat Polit├Ęcnica de Catalunya, Terrassa, Catalonia, Spain.