New development in the race to bring bionic eye closer to patients

A French company called Pixium Vision is testing a system called Iris that promises to improve the vision of the blind.

Notal Vision's ForeseeHome AMD Monitor receives FDA clearance

Notal Vision's ForeseeHome™ AMD Monitor has received Section 510 (k) clearance from the U.S. Food and Drug Administration (FDA).

The ForeseeHome AMD Monitor is the first ophthalmic device linking patients and doctors between eye exams for ongoing monitoring of age-related macular degeneration (AMD). 

Patients complete a frequent but brief exam on their ForeseeHome AMD Monitor, in the comfort of their own home, and data is transmitted to the patients' eye care physician and the Notal Vision Data Monitoring Center.  The award winning ergonomic design of the ForeseeHome AMD Monitor is comfortable and easy to use for patients at risk of vision loss from wet AMD.

Wet AMD is the leading cause of blindness in people over the age of 60 in the western world. Recent breakthroughs in treatments place even greater importance on early detection, which can reduce the risks of vision loss associated with wet AMD.  Frequent monitoring is critical in detecting disease onset as early as possible and the ForeseeHome AMD Monitor is the first home monitoring device for following patients at risk of vision loss, offering hope for early intervention through early detection.

Numerous clinical studies have demonstrated the ForeseeHome AMD Monitor is an accurate and reliable tool for frequent monitoring of patients at risk for vision loss from wet AMD.

FDA Indication for Use: 

ForeseeHome is intended for use in the detection and characterization of central and paracentral metamorphopsia (visual distortion) in patients with age-related macular degeneration as an aid in monitoring progression of disease factors causing metamorphopsia including, but not limited to choroidal neovascularization (CNV). It is intended to be used at home for patients with stable fixation. ForeseeHome is not intended to diagnose; diagnosis is the responsibility of the prescribing eye-care professional.

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Ohr Pharmaceutical initiates Investigator sponsored trial of squalamine eye drops in diabetic macular edema

Ohr Pharmaceutical, Inc., a research and development company with a primary focus in ophthalmology, has announced the initiation of a Phase II investigator sponsored clinical trial, OHR-005, testing Squalamine eye drops in patients with diabetic macular edema (DME).

The current standards of care for DME include chronic treatments of VEGF inhibitors administered directly into the eye via an injection. Squalamine eye drops may potentially represent a less-invasive treatment option for patients suffering from diabetic macular edema, as per the investigators of this trial. 

OHR-005 is a randomized, placebo controlled, investigator sponsored, multicenter Phase II clinical trial evaluating the effect of Squalamine Eye Drops in patients with DME. The primary endpoints will measure change in retinal thickness and change in Best Corrected Visual Acuity (BCVA) over 24 weeks. Secondary objectives include additional BCVA measurements, change in foveal thickness, evaluation of the need for rescue injections of ranibizumab (Lucentis®) and an assessment of the safety and tolerability of Squalamine Eye Drops. The trial is designed to enroll up to 30 subjects at 3 sites in the United States. Patients will be randomized to receive a single injection of ranibizumab at baseline followed by treatment with either Squalamine lactate ophthalmic solution 0.2% or placebo ophthalmic solution, administered QID for 24 weeks.

Squalamine is an anti-angiogenic small molecule with a novel intracellular mechanism of action, which counteracts multiple growth factors implicated in the angiogenesis process. Ohr Pharmaceutical has developed a novel eye drop formulation of Squalamine for the treatment of wet-AMD, designed for self-administration, which may provide several potential advantages over the FDA approved current standards of care, which require intravitreal injections directly into the eye. The drug, using an intravenous administration in over 250 patients in Phase I and Phase II trials for the treatment of wet-AMD, showed favorable biological effect and maintained and improved visual acuity outcomes. In May 2012, the Squalamine Eye Drop program was granted Fast Track Designation by the FDA. A Phase II randomized, double blind, placebo-controlled study (OHR-002) to evaluate the efficacy and safety of Squalamine Eye Drops for the treatment of wet-AMD has completed enrolling patients. Three additional investigator sponsored trials (IST) are evaluating Squalamine eye drops for the treatment of proliferative diabetic retinopathy, retinal vein occlusion and diabetic macular edema, with one additional IST expected to be initiated in diabetic macular edema in the second calendar quarter of 2014.

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QLT announces clinical & regulatory update for oral retinoid program for inherited retinal disease

QLT announced that, following meetings with the U.S. Food and Drug Administration and the European Medicines Agency, the Company believes that it is close to finalizing a pivotal trial protocol for QLT091001 for the treatment of inherited retinal disease such as Leber Congenital Amaurosis (LCA) and Retinitis Pigmentosa (RP) due to mutations in the LRAT and RPE65 genes, both orphan indications.

The Company expects to provide final guidance on its development plans in these indications before the end of the first quarter of 2014 after final feedback from the European regulatory agency.

Additionally, QLT has initiated recruitment of subjects for a Phase IIa proof-of-concept trial of its drug candidate, QLT091001, in adult subjects with Impaired Dark Adaptation (IDA), a condition that results in decreased ability to recover visual sensitivity in the dark after exposure to bright lights.

The Company also announced the launch of a compassionate use program for QLT091001 in LCA and RP, as well as plans for a patient registry and an update on its retreatment study in these indications.

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FDA approves Eylea for patients with Age-related Macular Degeneration

Regeneron Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has approved Eylea (aflibercept) Injection, known in the scientific literature as VEGF Trap-Eye, for the treatment of patients with neovascular (wet) Age-related Macular Degeneration (AMD) at a recommended dose of 2 milligrams (mg) every four weeks (monthly) for the first 12 weeks, followed by 2 mg every eight weeks (2 months).

The approval of Eylea was granted under a Priority Review, a designation that is given to drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists.  This approval was based upon the results of two Phase 3 clinical studies.  In these studies, Eylea dosed every eight weeks, following three initial monthly injections, was clinically equivalent to the standard of care, Lucentis® (ranibizumab injection) dosed every four weeks, as measured by the primary endpoint of maintenance of visual acuity (less than 15 letters of vision loss on an eye chart) over 52 weeks.  The most common adverse reactions (frequency of 5% or more) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.  The adverse event profile was similar to that seen with ranibizumab.

As per the experts, Eylea offers the potential of achieving the efficacy that the ophthalmic world had come to expect from the current anti-VEGF agents, but with less frequent injections and no monitoring requirements. This, as per these experts, may reduce the need for costly and time-consuming monthly office visits for patients and their caregivers.

About Eylea™ (aflibercept) Injection:

Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body.  Its normal role in a healthy organism is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs.  However, in certain diseases, such as wet age-related macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit abnormal increased permeability that leads to edema. Scarring and loss of fine-resolution central vision often results.  

Eylea, known in the scientific literature as VEGF Trap-Eye, is a recombinant fusion protein, consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration.  Eylea acts as a soluble decoy receptor that binds VEGF-A and placental growth factor (PlGF) and thereby can inhibit the binding and activation of these cognate VEGF receptors.

Eylea is indicated for the treatment of patients with neovascular age-related macular degeneration (wet AMD).  Eylea is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA.

The recommended dose for Eylea is 2 mg administered by intravitreal injection every four weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg once every eight weeks (2 months).  Although Eylea may be dosed as frequently as 2 mg every four weeks (monthly), additional efficacy was not demonstrated when Eylea was dosed every four weeks compared to every eight weeks.

There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including Eylea, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs with Eylea in clinical trials was low (1.8%).

Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections with Eylea and include endophthalmitis, traumatic cataract, and increased intraocular pressure.

About the VIEW 1 and VIEW 2 Clinical Studies:

The safety and efficacy of Eylea were assessed in two randomized, multi-center, double-masked, active-controlled studies in patients with wet AMD.  A total of 2412 patients were treated and evaluable for efficacy (1817 with Eylea) in the two studies (VIEW 1 and VIEW 2). In each study, patients were randomly assigned in a 1:1:1:1 ratio to one of four dosing regimens: 1) Eylea administered 2 mg every eight weeks following three initial monthly doses Eylea 2Q8); 2) Eylea administered 2 mg every four weeks Eylea 2Q4); 3) Eylea 0.5 mg administered every four weeks Eylea 0.5Q4); and 4) ranibizumab administered 0.5 mg every four weeks (ranibizumab 0.5Q4).  Patient ages ranged from 49 to 99 years with a mean of 76 years.

In both studies, the primary efficacy endpoint was the proportion of patients who maintained vision, defined as losing fewer than 15 letters of visual acuity at week 52 compared to baseline.  Data are available through week 52.  Both the Eylea™ (aflibercept) Injection 2Q8 and 2Q4 dosing groups were shown to have efficacy that was clinically equivalent to the ranibizumab 0.5Q4 group for the primary endpoint.

Select results of the VIEW 1 and VIEW 2 studies as described in the full Prescribing Information for the Eylea 2 mg every four weeks and Eylea 2 mg every eight weeks dosing groups as compared to ranibizumab dosed monthly group are shown below.

To check the efficacy outcomes at week 52 in VIEW 1 and VIEW 2 Studies, please click on the source below. 

Safety of Eylea:

Eylea™ (aflibercept) Injection is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in Eylea.

Intravitreal injections, including those with Eylea, have been associated with endophthalmitis and retinal detachments.  Proper aseptic injection technique must always be used when administering EYLEA.  Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with Eylea.  Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors.  Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately. There is a potential risk of arterial thromboembolic events (ATEs) following use of intravitreal VEGF inhibitors, including Eylea, defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).  The incidence of ATEs with Eylea in clinical trials was low (1.8%). Serious adverse reactions related to the injection procedure have occurred in less than 0.1% of intravitreal injections with Eylea including endophthalmitis, traumatic cataract, and increased intraocular pressure. The most common adverse reactions (greater than or equal to 5%) reported in patients receiving Eylea were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure.

To see the full prescribing Information for Eylea, please click here.

Regeneron is collaborating with Bayer HealthCare on the global development of Eylea.  Bayer submitted an application for marketing authorization in Europe for wet AMD in June 2011.

Bayer HealthCare will market Eylea outside the United States, where the companies will share equally the profits from any future sales of Eylea.  Regeneron maintains exclusive rights to Eylea in the United States.

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FDA Requests More Trials of Retinal Disease Treatment

Alimera Sciences, Inc., a biopharmaceutical company that specializes in the research, development and commercialization of prescription ophthalmic pharmaceuticals, today announced that it has received a complete response letter (CRL) from the U.S. Food and Drug Administration (FDA) in response to the New Drug Application (NDA) for ILUVIEN® for the treatment of diabetic macular edema (DME) associated with diabetic retinopathy.

A CRL is issued by the FDA's Center for Drug Evaluation and Research when their review of an application is completed and questions remain that precludes the approval of the NDA in its current form.

Alimera is seeking approval for Iluvien as a treatment for diabetic macular edema, a condition that can cause blurred vision and blindness.

The FDA stated that it was unable to approve ILUVIEN because there was no provide sufficient data to support that ILUVIEN is safe and effective in the treatment of patients with DME. The FDA stated that the risks of adverse reactions shown for ILUVIEN in the FAME® Study were significant and were not offset by the benefits demonstrated by ILUVIEN in these clinical trials. The FDA has indicated that Alimera will need to conduct two additional clinical trials to demonstrate that the product is safe and effective for the proposed indication.

The company officials will request a meeting with the FDA to clarify its next steps. 

ILUVIEN is Alimera's investigational, sustained drug delivery system that releases sub-microgram levels of fluocinolone acetonide (FAc) for the treatment of DME.

Alimera initially had asked the FDA to approve Iluvien in June 2010. In December, the FDA asked the company to report data from a third year of a clinical trial, and Alimera filed that data in May 2011. It also responded to the agency's concerns about manufacturing, packaging and sterilization of the drug. 

In December 2010, the FDA issued a CRL to Alimera related to its June 2010 NDA for ILUVIEN, which included data through month 24 of the FAME™ Study.

In that first CRL, the FDA asked for, among other things, analyses of the safety and efficacy data through month 36 of the FAME Study. Alimera submitted a response to the FDA on May 12, 2011, addressing the issues raised in the first CRL and including 36-month trial data. The FDA classified Alimera's response as a Class 2 resubmission, resulting in a six-month review period and a Prescription Drug User Fee Act, or PDUFA, date of November 12, 2011.

For Europe, Alimera expects to submit its formal response to the Preliminary Assessment Report to the Medicines and Healthcare products Regulatory Agency (MHRA) later this month. Based on this submission, the MHRA is expected to make a recommendation on the approvability of ILUVIEN to Alimera and the Concerned Member States (Austria, France, Germany, Italy, Portugal and Spain) by the end of this year, with a decision regarding the approval of ILUVIEN expected in the first half of 2012. The market opportunity in Europe is similar in size to the U.S. market opportunity.

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FDA grants orphan drug status for Santen Inc.'s Sirolimus (DE-109)

Santen Inc., the U.S. subsidiary of global ophthalmic pharmaceutical company Santen Pharmaceutical Co., Ltd. (Osaka, Japan), & Global Clinical Development and Medical Affairs at Santen today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for sirolimus (DE-109) for the treatment of chronic/refractory anterior non-infectious uveitis, non-infectious intermediate uveitis, non-infectious panuveitis, and non-infectious uveitis affecting the posterior segment of the eye. The designation follows the granting of orphan drug status by the European Commission in September 2011.

About Sirolimus: 
Sirolimus was isolated in the 1970’s from Streptomyces hygroscopicus in soil samples from  Easter Island. Sirolimus is the active pharmaceutical ingredient in two products approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), specifically, Rapamune®, an immunosuppressive agent used in renal transplant patients, and the CYPHER® Sirolimus-eluting Coronary Stent approved for improving coronary luminal diameter in patients with symptomatic ischemic disease.

Sirolimus, originally known as rapamycin, is a broad-acting compound that is known to be an immunosuppressive and anti-proliferative agent. It is currently being evaluated in a Phase III study entitled SAKURA (Study Assessing double-masKed Uveitis tReAtment), to assess the safety and efficacy of different doses of sirolimus in non-infectious posterior uveitis. (If you are an expert and want to know the clinical trial details, please click here.)

About Uveitis:
Uveitis is a group of intraocular inflammatory disorders with both infectious and autoimmune  etiologies. Typically uveitis is classified by anatomic location in the uvea. Anterior uveitis is the most common type and can involve the cornea, iris, and/or ciliary body. Intermediate uveitis affects the middle portion of the eye, such as the ciliary body and vitreous. Posterior uveitis can involve the vitreous, choroid, retina, and/or optic nerve. Panuveitis, also referred to as diffuse, can encompass anterior, intermediate, and posterior segments. 

Lasers may be increasing threat to the eye and the retina

An article in the New York Times by Christine Negroni refers to the increasing threat to vision and damage to the retina, by increasing access to the green laser.

Eye doctors around the world are warning of increasing number of cases of teenagers who suffer permanent eye damage while playing with high-powered green laser pointers.

The pointers, which have also been implicated in a ninefold increase over five years in reports of lasers’ being aimed at airplanes, are easier than ever to order online, even though they are 10 to 20 times as powerful as the legal limit set by the Food and Drug Administration.

A recent case highlights the problem: A high school student complained of a blind spot in his left eye, when a friend waved a green laser pointer in front of his face. The damage, as diagnosed by a retina specialist, was found to be severe and is not likely to completely heal, which means the high school student may end up with a permanent damage to his vision. The same retina specialist found out that the laser put out 50 milliwatts of power, 10 times more than the F.D.A. limit. And as he investigated his patient’s case, the doctor went online and bought a 100-milliwatt pointer for $28 (about Rs 1255) , and was hardly able to believe that he could buy an even more stronger laser without any controls or checks in place.

Like household lights, lasers are measured in watts, but the similarity ends there. A 100-watt incandescent bulb produces about five watts of visible light; the five-milliwatt laser is only one-thousandth as powerful. But because the light from a bulb is diffuse while a laser beam is concentrated, the effect of five milliwatts on the eye is 10,000 times as intense, according to laser experts. (For technical information on lasers, click here.) It also does not help that the eye tends to focus and intensify the laser, causing even more damage to the main part of the retina, the macula or the fovea, which is the center of the retina. The darker pigment present in the region absorbs the light as heat, quickly raising the temperature of the retina.

Some experts feel that the sale of laser pointers more than one milliwatt should be banned to the general public, since the stronger laser put people at risk of permanent visual impairment by the criminally minded or those who are unaware of the risks.

F.D.A., in its update, warned that a higher-powered laser gives less time to look away before injury can occur, and as power increases, eye damage may happen in a microsecond. One company that has come under scrutiny from the FDA is Wicked Lasers from Hong Kong.

Several laser experts feel that the enforcement of regulations is insufficient and ineffective. But any new restrictions being put in to contain the availability of such lasers will certainly meet resistance from the large community of laser enthusiasts, including those who use them professionally (like contractors and astronomers) and hobbyists.

Earlier, red lasers were used as laser pointers, Now, green lasers are more commonly used. But green lasers are also more dangerous. Green is more easily absorbed by the retina than red, so it requires less exposure to cause damage.

As a recommendation, please do not allow lasers to fall into the hands of unsuspecting children, who may find it easy to point the laser light at others, which can potentially be permanently damaging. Also, educate everyone who uses laser pointers to be more careful, including colleagues at work, who have the tendency of using the laser pointer during presentations, and who have the tendency of sweeping their hands around with the laser pointer turned on!