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.

Source

New treatments for Age-related Macular Degeneration and Stargardt's disease

Elderly people losing their vision from age-related macular degeneration might one day have a treatment option that requires fewer injections into the eye than the standard drug now used.

In testing, an experimental drug being developed by Regeneron Pharmaceuticals, when injected every eight weeks, proved as effective as the standard treatment, Lucentis from Genentech, which was injected every four weeks. The findings are from two clinical trials that Regeneron is expected to announce on Monday.

In a separate development, Advanced Cell Technology is expected to announce Monday that it has won regulatory approval to test a therapy derived from human embryonic stem cells in people with Stargardt’s macular dystrophy, another retina disease.

It is only the second trial of a therapy derived from human embryonic stem cells to be cleared by the Food and Drug Administration. The first involves a treatment for spinal cord injury developed by Geron.

Age-related macular degeneration is the leading cause of blindness in the elderly. Lucentis can restore a person’s ability to drive and read, in some cases.

But the drug works best when given every four weeks, which can be inconvenient for patients and doctors. Doctors often give Lucentis less frequently, but even if that regimen produces good results, patients must still get checkups every month to make sure their vision is not deteriorating.

Regeneron’s drug, which is called VEGF Trap-Eye, “gives us the opportunity to not have to see them monthly,” said Dr. Jeffrey Heier of Boston, an investigator in one of the trials and a consultant to Regeneron. That would be “very meaningful to patients and their families,” he said.

Regeneron and its partner, Bayer, said they planned to apply for approval of the drug in the first half of 2011.

The two similar trials involved a total of 2,457 patients who were randomly chosen to receive either Lucentis every four weeks or VEGF Trap-Eye either every four weeks or every eight weeks. In the eight-week arm, the first three doses were given every four weeks.

After a year, roughly 95 percent of the patients in all the arms of the trial maintained their vision, meaning their ability to read an eye chart declined by no more than 15 letters, or three lines.

VEGF Trap-Eye was also “noninferior” to Lucentis in terms of the average change in vision after one year. Lucentis recipients had a mean gain of 8.1 letters and 9.4 letters in the two trials. Those getting Regeneron’s drug every eight weeks had gains of 7.9 letters and 8.9 letters. Regeneron said the two drugs were equally safe.

Both VEGF Trap-Eye and Lucentis block a protein called vascular endothelial growth factor that causes blood vessels to grow and leak into the eye.

VEGF Trap-Eye could become the first big product for Regeneron, which was founded in 1988 and is based in Tarrytown, N.Y. It sells one drug for a rare disease and has garnered hundreds of millions of dollars from licensing deals with big pharmaceutical companies.

Regeneron’s drug is likely to face competition from off-label use of Genentech’s cancer drug Avastin. When used in the eye, Avastin costs about $50 a dose, compared with about $2,000 for Lucentis. Still, even with such low-priced competition, Lucentis has sales exceeding $2 billion globally.

Meanwhile, Advanced Cell Technology, of Marlborough, Mass., said it would test its stem cell therapy on 12 adults with severe vision loss caused by Stargardt’s, an inherited disease.

The company has turned human embryonic stem cells into retinal pigment epithelial cells, which will be surgically implanted into the eye. The hope is that the implanted cells will replace those injured by the disease.

Human embryonic stem cells are controversial because their creation usually entails the destruction of human embryos, although Advanced Cell Technology is working on a technique to avoid that.

Embryonic cells can also form tumors if injected into the body. Dr. Robert Lanza, chief scientist at Advanced Cell, said the company had to prove to the F.D.A. that its retinal cells contained virtually no residual embryonic stem cells. It took a year for the company to get clearance for the trial from the F.D.A.

It is likely to be several years before such a treatment can reach the market, if it works. Still, even starting the trial could be a boost to Advanced Cell, which often makes headlines but has struggled to raise money. Its shares closed at 5 cents on Friday.

Dr. Peter J. Francis, an associate professor at the Oregon Health and Science University, which will be a site for the trial, says the eye is a good place to test stem cell therapy because it is accessible. Also, he said, there is less chance of rejection of the implanted cells because the eye is shielded somewhat from the body’s immune system.

There is no treatment for Stargardt’s, which affects more than 25,000 people in the United States (and about 1 lakh people in India). The disease is usually diagnosed during childhood and it causes a loss of central vision, though not usually peripheral vision.

From the New York Times

Note from Retina India:
Retina India is creating registries or databases of patients with macular degeneration and Stargardt's disease. If you, or someone you know has the above diseases, or any other retinal disease, please write to info@retinaindia.org to be included in the database. Retina India also runs Connect Programs, which allow patients and family members interested in one particular diseases (e.g. Stargardt Connect) to connect with each other, which allows them to discuss and resolve their problems.