Sirion Therapeutics announced the commercial availability of Durezol (difluprednate ophthalmic emulsion) 0.05%, which was approved by the Food and Drug Administration in June 2008. The topical ophthalmic corticosteroid is indicated for the treatment of inflammation and pain associated with ocular surgery.

Sirion also announced the completion of two Phase IIIb studies that evaluated Durezol for the management of postoperative inflammation in which treatment was initiated one day prior to surgery. The multicenter, randomized, double-masked, placebo-controlled, parallel-group trials were conducted in 245 patients undergoing unilateral ocular surgery. In the first study of 124 patients, Durezol or placebo was dosed four times daily (q.i.d.), while in the second study, 121 patients received Durezol or placebo twice daily (b.i.d.).

"The Phase IIIb studies represent an approach to therapy that is most similar to the current standard of care, meaning most physicians treat inflammation prophylactically rather than waiting for it to occur," explained Steven Silverstein, MD, of Silverstein Eye Centers. Dr. Silverstein was a principal investigator in the q.i.d. study and also serves as a clinical assistant professor of ophthalmology at the University of Missouri-Kansas City School of Medicine and the University of Health Sciences. "Overall, the results from these studies show that by any definition utilized, Durezol administered both b.i.d. and q.i.d. was more effective than placebo in treating postoperative ocular inflammation and relieving ocular pain/discomfort as early as day 3/4."

A significantly greater percentage of patients receiving Durezol q.i.d. or b.i.d. achieved a clinical response (defined as less than or equal to five anterior chamber cells and no flare) by day 14: 81.3 percent of the Durezol-treated patients in the q.i.d. group had a clinical response versus 25 percent of the placebo q.i.d. group (p<0.0001); 74.7 percent of the Durezol b.i.d. patients had a clinical response versus 42.5 percent of patients in the placebo b.i.d. group (p<0.001). Both Durezol groups maintained superiority over the placebo groups through day 28, demonstrating that efficacy was definitive and did not decrease or reverse over time.

Ocular pain/discomfort was measured using the Visual Analogue Scale score of 0 (no pain) to 100 (maximal pain). The percentage of patients who were free of ocular pain/discomfort, reflected by a VAS score of 0, was superior and statistically significant for the Durezol groups versus the placebo groups in both the q.i.d. and b.i.d. studies as early as day 3/4 and throughout the study period.

Six percent of the Durezol q.i.d. patients and 3.7 percent of the Durezol b.i.d. patients experienced a criterion increase in intraocular pressure, defined as a pressure of >=21 mmHg and a change from baseline >=10 mmHg at the same visit, compared with 0 percent in both of the placebo groups.

"Durezol has shown efficacy across multiple endpoints, including pain reduction. I believe it provides a potent new treatment option with a favorable safety profile," said Dr. Silverstein. "It is a welcome improvement to the armamentarium of ocular pharmaceuticals, particularly since ocular inflammation is common to the majority of conditions that ophthalmologists treat."

The recommended dosage and administration of Durezol is to instill one drop into the conjunctival sac of the affected eye(s) four times daily beginning 24 hours after surgery and then continue throughout the first two weeks of the postoperative period, followed by two times daily for a week with tapering based on the response.

 

NeoVista Releases Results on AMD Combo Therapy

NeoVista has released 18-month data from the company's Phase II feasibility study examining its novel epiretinal brachytherapy for treatment of wet age-related macular degeneration. The long-term data from the study, Durezol Launch (continued)

which was initiated to test the safety and efficacy of their therapy when used in conjunction with Avastin (bevacizumab), showed a marked advancement in mean visual acuity results at month 18, while only a limited number of patients required additional injections of Avastin. NeoVista's therapy applies a targeted dose of beta radiation to the leaking blood vessels that affect central vision; concomitantly, two injections of an anti-vascular endothelial growth factor agent are delivered to maximize the acute therapeutic response. Preliminary data show that NeoVista's targeted radiation therapy can be safe for both the patient and the physician, and may be able to restore the patient's vision. The current standard of care for wet AMD requires persistent injections of anti-VEGF drugs for an indefinite period. The ongoing, multicenter feasibility study enrolled 34 trial participants (mean age: 72 years) at two centers in Brazil and one in Mexico. These patients, with predominantly classic, minimally classic, or occult (with no classic) choroidal neovascularization, received a single 24 Gy treatment of NeoVista's epiretinal brachytherapy in combination with two intravitreal injections of Avastin, one dose prior to or at the time of radiation delivery and another one month later, depending on which arm of the trial the patient was enrolled in. Additional therapy was delivered based upon the investigator's evaluation of disease activity.

Analysis of 18-month follow-up on the first 25 trial participants to reach that milestone shows a mean improvement in visual acuity of 10.7 ETDRS letters; 96 percent of patients lost 15 letters or fewer, 76 percent gained some letters, 44 percent gained 15 or more letters, and 8 percent gained 30 or more letters. Of particular interest, 68 percent of the patients in the study did not require additional injections of Avastin throughout the 18-month period and the average number of additional injections within this subset was only 2.4 injections by month 18.

Most of the limited number of adverse events were related to the vitrectomy procedure (retinal tear, retinal detachment, subretinal hemorrhage, and vitreous hemorrhage), rather than the epiretinal brachytherapy. To date, no instances of radiation toxicity have been reported by the Doheny reading center. NeoVista continues to enroll patients in the company's pivotal trial, CABERNET. CABERNET is a multicenter, randomized, controlled study that will enroll 450 subjects at 45 sites worldwide, evaluating the safety and efficacy of NeoVista's epiretinal brachytherapy delivered concomitantly with the FDA-approved anti-VEGF therapy Lucentis (ranibizumab) versus Lucentis alone.

 

Akorn Debuts New Ocular Anesthetic

Akorn Inc. has launched Akten Gel 3.5%, a topical ocular anesthetic ophthalmic drug product, the first FDA-approved drug product indicated for use as an ocular anesthetic in four decades. Akten is the only approved ocular gel formulation that also contains the highest concentration of lidocaine. The company says Akten has several unique features: It is preservative-free, non-toxic to the cornea, does not sting due to its physiological pH and can be stored at room temperature. Akten can be used as a local anesthetic indicated for ocular surface anesthesia during cataract/glaucoma surgery, intravitreal injections for retinal disorders, retina surgery, and miscellaneous ocular procedures both in hospital/clinics and office based practices.

The results of a Phase III clinical trial for Akten were published in Ophthalmic Surgery, Lasers & Imaging; September/October 2008, "Lidocaine Hydrochloride Gel For Ocular Anesthesia: Results of a Prospective Randomized Study."

 

Study Finds Fault with FPT

Data from the Baltimore Pediatric Eye Disease Study, the first large, population-based study of eye disorders in preschool children, suggests that the commonly used fixation preference test is so inaccurate that its usefulness is questionable.

The study evaluated visual acuity in 1,504 children aged 30 to 71 months. The children were evaluated in a series of vision tests, including the fixation preference test and the Amblyopia Treatment Study test. The FPT measures the ability to focus images on the macula; the ATS measures visual acuity in children 30 months and older. "Decreased" visual acuity in study participants was assessed by comparing the children's results to normal vision standards for their age groups. Tests were repeated for all subjects 60 days later with children wearing corrective eyewear, if needed. Overall, the prevalence of decreased visual acuity was low: 1.2 percent in white children and 1.8 percent in black. Prevalence at retesting, with corrective eyewear as needed, was 0.5 percent in whites and 1.1 percent in blacks. Differences between the two ethnic groups were not statistically significant. The most common cause of decreased acuity at initial testing was refractive error. Only one child was found to be legally blind.

The researchers found that FPT, considered the clinical standard for testing vision in preverbal children and the only test widely available to eye specialists for this age group, did not accurately identify the presence or absence of visual acuity problems in this study population. The inaccuracies became apparent when ATS and FPT results were compared for children able to perform both tests.

"These results call into question the use of FPT for clinical decision making," said lead researcher David S. Friedman, MD, PhD, of the Wilmer Eye Institute at Johns Hopkins School of Medicine. "Given its poor performance, the accuracy of clinical interventions based on FPT is questionable, as are studies that use FPT as an outcome measure. If the experience of this study can be generalized, the use of FPT should be reconsidered." The report was published in October's Ophthalmology.

 

National Panel Report: We Back McCain

Citing such factors as his views on health care and his leadership ability, physicians on our National Panel favor Arizona Senator John McCain in the presidential election. For this survey, 46 of 500 panelists (9 percent) responded. Besides voicing their support for a candidate, the respondents also weighed in on which issues were most important to them.

Sixty-one percent of the panelists say they'll vote for Senator McCain, while 37 percent prefer Illinois Senator Barack Obama. In terms of party affiliation, 52 percent identify themselves as Republican, 24 percent as Democrat, 22 percent as independent and 2 percent as a member of another party. The McCain backers cite his experience and worries over Senator Obama's potential tax policies; the latter's supporters want to avoid four more years of policies they feel have failed the country. Feelings are strong on both sides.

"Senator Obama has the shortest resume and least experience of any candidate in my lifetime," says Little Rock, Ark., surgeon George Schroeder. Walter Lee Wright of Kinston, N.C., feels Mr. Obama is too soft on defense. "Obama will not protect the United States militarily or with a missile defense," he says. "And he'll tax job-producing businesses and entrepreneurism."

"I feel more secure with McCain," says a surgeon from Los Angeles. "He's more experienced and less likely to drift to the extreme. Also, I'm voting my pocketbook."

Mr. Obama's supporters are just as fiery. "Obama is intelligent," says Arthur Fleming Jr., MD, of Pittsburgh. "There is a good and obvious reason why McCain graduated fifth from the bottom of his class at Annapolis." Seattle's Richard Bensinger, MD, questions Senator McCain's judgment: "He's angry. And his first major decision is Palin? Who is he kidding?"

"I can't stand another eight years of the same stuff," says a Florida surgeon who's voting for Senator Obama. Using a numerical score (5=very important, 1=lowest importance) panelists rated the domestic and international issues they felt were important to them. Domestically, physician payment reform (rank: 4.2), homeland security (4.1) and the economy and jobs (3.9) topped the list. In international affairs, the war on terrorism (4.3) and the management of the Iraq war (3.9) were the important issues. "A successful terrorist attack on the United States now will topple the economy," says Dr. Wright in reference to the importance of homeland security. "What difference will social and environmental issues make then?" An Indiana Obama partisan disagrees, saying, "Policy on human rights and justice, both domestic and foreign, is always the most important issue to me, and supports every other issue."

Physicians also feel the health-care system is in need of a change: 58 percent think the system should feature 10 to 12 levels of service, with different co-payments and premiums, for individuals to choose from; 23 percent favor a single-payor system similar to Great Britain's. Only 5 percent favor no change. "This is a difficult question to answer," muses a physician from Delaware. "It may be a combination. [Altering the health-care system] is going to be tough for the American public. We need to maintain quality care and control costs, yet everyone wants it all. Patients will need to assume more responsibility for their care and their coverage."