Panel Won't Approve Single-bottle Bromday
At Press Time
Panel Won't Approve Single-bottle Bromday
Study may be needed to validate postop bilateral use.
By Samantha Stahl, Assistant Editor
■ A recent meeting of the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee voted against the idea of labeling a single bottle of NSAID drops for use in both eyes after cataract surgery.
The FDA's Center for Drug Evaluation and Research (CDER) was asked to approve an increased fill size of topical NSAID drops to allow patients going through two cataract surgeries to treat both eyes with a single bottle. The request came from Ista Pharmaceuticals regarding the company's Bromday (bromfenac ophthalmic solution 0.09%) drops. Ista sought to increase the fill size from 1.8 mL to 2.4 mL, a size still smaller than most topical NSAIDs, due to Bromday's once-a-day indication for postop pain and inflammation.
Wiley Chambers, MD, deputy director of the division of transplant and ophthalmology products for the CDER, requested the panel discussion to review postoperative drop use in more than one eye, since the issue had not previously been considered by the CDER.
The panel was asked to vote on whether it is “appropriate to use a single bottle of anti-inflammatory ophthalmic drops to treat both eyes postoperatively.” Five panel members voted yes, four voted no and two abstained.
To clarify confusion about the wording of the question, the panel was also asked: “Is it appropriate to label a single bottle of anti-inflammatory ophthalmic drops to treat both eyes postoperatively?” Only one member voted yes, 10 voted no and none abstained. Lack of evidence to support the safety of a single bottle for both eyes was cited as the chief reason for voting against the labeling.
Mark Packer, MD, of Eugene, Ore., who testified at the hearing on behalf of ASCRS, said the increase in fill size would have benefits to both patients and doctors. “I felt like the FDA was being penny-wise and pound-foolish,” he said. “A larger fill size would account for missed drops, and could eliminate the need for an extra refill, which is just a waste of time and money for patients.”
He explained that to officially change the label, a postop study would likely need to be completed that reassures the safety of using one bottle for both eyes. Currently, there is no data that has confirmed what he calls the “phantom risk” for spreading infection from one eye to another with a bottle.
“There was a broad level of support for the utility of a larger fill size in line with current standards of practice,” said an Ista Pharmaceuticals spokesperson. While there was no official vote, only discussion, the panel “also supported creating additional language for packaging that advises patients to avoid contact with the top of the bottle and to wash hands before using as a way of further mitigating the potential risk of contamination and infection.”
Ista will now wait on the FDA's final decision concerning Bromday's labeling. In the meantime, the company will continue to offer the drug in a twin pack with a smaller bottle size. Ista says it will also take the panel's discussion into consideration as it files its NDA submission for Prolensa (bromfenac ophthalmic solution), for which it hopes to have a larger fill size approved.
|In the News
■ Avedro files NDA for keratoconus treatment. Avedro has submitted a new drug application to the FDA for its VibeX (riboflavin ophthalmic solution)/KXL System for the treatment of keratoconus and corneal ectasia following refractive surgery.|
“We are pleased to have submitted our positive results from the first multi-site US clinical studies on corneal collagen cross-linking to the FDA,” said David Muller, PhD, CEO of Avedro. “The VibeX/KXL System NDA submission represents an important milestone towards making cross-linking available to patients suffering from keratoconus and post-LASIK ectasia in the US.”
The VibeX/KXL System for corneal collagen cross-linking received CE Mark in 2010 and has been commercially available internationally since that approval.
■ Trial begins for incision-closing device. Ocular Therpeutix has received approval from the FDA to conduct a pivotal clinical trial with ReSure Sealant, a proprietary synthetic hydrogel polymer for clear corneal incision closure.
The randomized, parallel-arm clinical trial will test the safety and efficacy of the device, relative to sutured closure, for prevention of postoperative fluid egress on clear corneal incisions following cataract or intraocular lens placement surgery. The trial will be conducted at up to 24 sites throughout the United States.
■ Visian ICL paces Staar growth. Staar Surgical reported that revenue for the fourth quarter of 2011 grew 14% to $16.4 million, while the company showed an adjusted $1.5 million profit for the quarter. Fourth-quarter performance was driven by a 37% increase in Visian ICL (phakic IOL) product sales which, at $9 million, set another quarterly record.
Strong sales momentum for the Visian ICL continued to drive Staar financial results, resulting in double digit revenue growth and continued expanding gross profit margins.
■ B+L to acquire Ista. Bausch + Lomb and Ista Pharmaceuticals have signed a definitive agreement under which B+L will acquire Ista for $9.10 per share in cash, or a total of approximately $500 million. The transaction, which has been unanimously approved by the boards of directors of both companies, is expected to close in the second quarter of this year.
Bausch + Lomb said its acquisition of Ista accelerates the company's strategy to strengthen its pipeline and marketed products and capabilities.
The combination adds Ista's portfolio, including the widely used NSAID Bromday, plus allergy, glaucoma and spreading agents, to Bausch + Lomb's complementary portfolio of existing prescription ophthalmology and OTC eye health products.
Valeant Pharmaceuticals had previously made an attempt to acquire Ista but Ista management rejected the $7.50 per share offer as insufficient and said it would study other options to maximize shareholder value.
■ Dry eye drug in phase 3 study. SARcode Bioscience said it has completed patient enrollment in its first pivotal phase 3 clinical study (OPUS-1) of SAR 1118 ophthalmic solution. SAR 1118 (to be called lifitegrast) is a first-in-class small-molecule integrin antagonist that inhibits T-cell inflammation by blocking the binding of two key surface proteins (LFA-1 and ICAM-1) that mediate the chronic inflammatory cascade associated with dry eye disease.
OPUS-1 is a randomized, double-masked study evaluating the safety and efficacy of SAR 1118 5.0% ophthalmic solution compared to placebo over a 12-week period. A total of 588 patients with dry eye disease have been enrolled at 13 clinical sites across the US. The primary endpoints in this study will assess both a sign and a symptom of dry eye disease, and include corneal fluorescein staining score and vision-related function score (reading, driving at night, computer use, watching television) as measured by the Ocular Surface Disease Index.
■ Spectralis anterior segment module approved. Heidelberg Engineering said the FDA has granted clearance for the new Spectralis Anterior Segment Module. The Module provides high-resolution images of cornea, anterior chamber angle and sclera utilizing unique Heidelberg Noise Reduction technology for enhanced detail. Heidelberg says clinicians can assess both chamber angles at the same time using a 16 mm-wide angle-to-angle OCT scan.
“The Anterior Segment Module paves the way towards digital gonioscopy”, said Sanjay Asrani, MD, Associate Professor of Ophthalmology at Duke University Eye Center. “Glaucoma surgeons will further benefit from the enhanced depth imaging OCT capabilities of Spectralis when assessing filtering blebs and anterior chamber angles.”
■ PowerVision funds accommodative IOL research. PowerVision, Inc., which is developing an accommodating premium IOL, has closed its Series C financing round with a total of approximately $37.2 million in venture capital funding. The money will be used in the company's ongoing R&D activities as well as its clinical trial targeted at achieving the CE Mark in Europe.
PowerVision says its novel IOL technology uses fluids inside its lens in combination with natural muscle forces in the eye to create a shape change in its lens, restoring accommodative function. PowerVision says its technology has the potential to create an average of 5 or more diopters of power change, therefore creating true independence from spectacles or other corrective lenses.
PowerVision's products are not yet approved or cleared by the FDA for sale in the US.
Criteria for Drug Approvals
Critic: Safety best basis for FDA decisions.
By René Luthe, Senior Associate Editor
■ The FDA approval process is so slow and outdated, says a former agency commissioner, that the United States is in real danger of losing its pre-eminence in the global biomedical market. In a recent op-ed piece in the Wall Street Journal, Andrew von Eschenbach, who served at the FDA from 2005-2009, recommends a policy of approving drugs based on proof of concept and safety testing, leaving demonstration of efficacy for post-market studies.
Due to some well-publicized cases of unanticipated side effects of drugs such as Vioxx, the FDA has required more data and longer clinical trials from manufacturers to identify rare side effects. Mr. von Eschenbach cites The Tufts Center for the Study of Drug Development report that clinical trials from 2003-2006 were nearly 70% longer than those from 1999-2002. The result is “skyrocketing” drug development costs that crowd out investments in new therapies for such significant health threats as diabetes, obesity and heart disease. He also cites macular degeneration as a disease where new concepts such as stem cell therapy should be allowed to move ahead more quickly.
An additional danger the FDA's current modus operandi poses, says Mr. von Eschenbach, is of an economic nature: “The US biomedical industry of the American economy. It employs 1.2 million people directly and over five million throughout its supply chain, with a total output of $519 million,” he says, citing a 2011 Milken Report claiming that from 2001 to 2010, US-based companies produced approximately 60% of the new medications globally. “But US firms won't continue to lead unless the FDA retains its role as the world's ‘gold standard’ for evaluating new medical products.” Israel, China and Singapore are among the countries poised to “leapfrog” US leadership in the life-sciences industry, he warns.
In a reader comment posted by Allan May, chairman of Life Science Angels, a company that tracks venture capital investments in healthcare, Mr. May notes that the FDA's slow pace is “rapidly forcing the off-shoring of the US's vaunted medical device and biotech industries. This is not a future threat; it is a present reality.” He notes that the system advocated by Mr. Eschenbach, of products approved after they demonstrate safety, followed by efficacy studies once they are on the market, is the system already used in Europe — a continent for whose residents numerous studies have shown life expectancy and quality of life at least equal to those of patients in the United States.
A cause of serious eye infections?
■ Scientists from the Schepens Eye Research Institute have found for the first time that a bacterial pathogen can literally mow down protective mucins found on mucus membranes to enter and infect a part of the body. Their landmark study on the phenomenon, published recently in the journal PLoS ONE, describes how they discovered that an “epidemic” strain of the bacterium Streptococcus pneumoniae, which causes conjunctivitis, secretes an enzyme to damage mucins and breach the mucosal membrane to infect and inflame the eye.
“We are excited about this finding,” says Ilene Gipson, PhD, the study's principal investigator and a senior scientist at the Schepens. “Our discovery may ultimately lead to new ways of diagnosing, treating and preventing bacterial infections originating not only in the eye but in other parts of the body as well.”
Until the current PLoS ONE study, little has been known about how epidemic infection-causing bacteria are able to cross through the mucin barrier. Experts in the study of mucins determined to find a piece of this puzzle, the Schepens scientists hypothesized that “epidemic” bacteria must somehow remove the mucins themselves.
To test their hypothesis, the team grew “epidemic” conjunctivitis bacteria (a strain of Streptococcus pneumoniae) in a culture. This bacteria causes an inflammation of the conjunctiva. They then applied the fluid that the bacteria were cultured in to cell lines that mimicked the eye's surface, including presence of intact mucins, and found that the membrane-anchored mucins were cut off and released from the surface of the cells. Removal of the mucins allowed the bacteria to enter the cells.
Using mass spectrometry, the researchers were then able to identify the enzyme ZmpC as the culprit. They confirmed their findings by knocking out the gene in the bacteria that produced this enzyme and demonstrated that the bacterium could no longer remove the mucins from the membrane.
According to Dr. Gipson, “This discovery is a major breakthrough in this long unsolved puzzle about how ‘epidemic’ bacteria enter the body and has given us a new target for drugs that could even be used preventatively.”
The next step in the research, according to Dr. Gipson, will be to determine if the method of enzymatically removing the surface mucins to gain entrance is used by other disease-causing bacteria.
|Preview of ARVO 2012|
This meeting is a treasure trove of vision research.
By Jerry Helzner, Senior Editor
The Association for Research in Vision and Ophthalmology annual meeting will be winding up a long run at the Broward County/Greater Fort Lauderdale Convention Center May 6 through 10 before going on the road for the next several years.|
Future annual meetings are scheduled for Seattle (2013), Orlando (2014) and Denver (2015) and Seattle again (2016).
This year's meeting promises to offer a wealth of new research that will be of interest to ophthalmologists and vision researchers. The breadth and depth of the more than 6,000 pieces of research that will be offered via presentations, posters, lectures and symposia can be easily ascertained by putting almost any key word in the search box for this year's abstracts. The word “glaucoma” is mentioned in more than 1,100 abstracts, “cataract” in more than 550, “keratoconus” in 129 and “endophthalmitis” in more than 100 research presentations.
Interestingly, femtosecond-assisted cataract surgery is mentioned in only a handful of abstracts, probably because of the intense coverage of that timely topic at this year's ASCRS meeting.
Dr. Venter to Give Keynote Speech
With an expected attendance of 12,000 researchers representing approximately 80 countries, this year's ARVO meeting will feature the theme: “Translational Research: Seeing the Possibilities.” The keynote address, to be delivered on Sunday, May 6 at 5:45 pm, will be given by J. Craig Venter, PhD, of the J. Craig Venter Institute and Synthetic Genomics, Inc. Dr. Venter's presentation is titled “From Reading to Writing the Genetic Code.”
Dr. Venter is regarded as one of the 21st century's leading scientists. His numerous contributions to genomic research include publication of the first draft human genome in 2001, the first complete diploid human genome in 2007 and the creation of the first self-replicating bacterial cell constructed entirely with synthetic DNA.
He is founder, chairman and president of the J. Craig Venter Institute, a nonprofit organization with approximately 300 scientists and staff dedicated to human, microbial, plant, synthetic and environmental genomic research, and the exploration of social and ethical issues in genomics.
Dr. Venter is also founder and CEO of Synthetic Genomics, a privately held company developing and applying genomic-driven commercial solutions to markets including biofuels, biochemicals and new bio-based food products.
Annual Award Winners
Four major prestigious awards are given at every ARVO meeting. Unfortunately, Josh Wallman, PhD, of the City University of New York, the winner of the Friedenwald Award for championing the chick as an animal model for myopia, died recently.
The other award winners include Peter Sterling, PhD, from the University of Pennsylvania School of Medicine, who will receive the Proctor Medal for outstanding research in the basic or clinical sciences as applied to ophthalmology. Dr. Sterling is being honored for career achievements, especially in the area of the relationship between function and structure in visual information processing.
The Weisenfeld Award, presented in recognition of distinguished scholarly contributions to the clinical practice of ophthalmology, will go to John V. Forrester, MD, ChB, of the University of Aberdeen, Scotland, for his academic publications relating to clinical ophthalmology, basic eye research, immunology and cell biology. He is also being honored for creating one of Europe's finest ophthalmology departments and training/mentoring numerous MDs and PhDs.
The Cogan Award, presented to a researcher under 40 years of age who has already made substantial contributions to research in ophthalmology and visual science with the promise of even greater achievements to come, will be given to Jeffrey Goldberg, MD, PhD, of Bascom Palmer Eye Institute. Dr. Goldberg has been doing laboratory research directed at neuroprotection and regeneration of retinal ganglion cells, and has contributed significant discoveries about the failure of optic nerve regeneration.
Key Areas of Research
This year's presentations will delve heavily into such timely topics as keratoconus, endophthalmitis and macular degeneration. The new directions in treatments for keratoconus is a particularly compelling topic as many studies are either under way or being completed in the emerging area of corneal cross-linking. Though still investigational in the United States, corneal cross-linking has shown great promise and is now being used extensively and routinely in Europe.
Many of the corneal collagen cross-linking studies now underway aim to determine the most effective way to provide this treatment, as several approaches and techniques are currently being tried, with different degrees of success. The great promise of collagen cross-linking is that this treatment can halt the progression of keratoconus and improve vision — eliminating the need for an invasive corneal transplant procedure, which would normally be the next step in severe cases of keratoconus (and post-LASIK ectasia). Ophthalmology Management will be reviewing a number of ARVO keratoconus presentations in a feature article in our May issue.
Another area of great interest — and concern — is endophthalmitis, which has been in the headlines in the past year due to cases stemming from tainted Avastin, contaminated intraoperative dye and possible transmission due to lax intravitreal injection protocols.
Finally, there is great interest in second-year data from the much-publicized CATT trial comparing the effectiveness and safety of Lucentis and Avastin for the treatment of wet AMD. Though no formal announcement has been made that the two-year data will be released at ARVO, there are hints that the results will be discussed at this meeting.
On The Lighter Side
One “can't miss it” event each year is ARVO Rocks, which will be held Tuesday, May 8 from 9 pm to midnight in the Caribbean Ballroom of the Marriott Harbor Beach hotel. This high-energy event is an ARVO tradition, featuring classic rock performed by ARVO members and other musicians. OM
Ophthamology Management, Volume: 16 , Issue: April 2012, page(s): 10 - 16