SUBSPECIALTY NEWS

Regeneron Sets Future Direction

Provides broad overview of strategic path.

BY JERRY HELZNER, SENIOR EDITOR

■ Speaking at the recent Goldman Sachs Annual Global Healthcare Conference, Michael Aberman, MD, Regeneron vice president of Strategy and Investor Relations, provided a carefully stated but informative outline of how the company intends to build upon its initial major success with its Eylea (aflibercept) anti-VEGF treatment for retinal diseases. One piece of new information he offered was that the company has been working with the FDA to obtain approval for a pre-filled syringe version of Eylea, rather than the vials that are currently used for all anti-VEGF eye drugs.

Dr. Aberman said the FDA has set “a high hurdle” for pre-filled syringe packaging to ensure sterility at every step of the process from manufacturer to the time the physician opens the blister pack and performs the injection.

He also hinted that the positive results from a “competitor’s” recent combination anti-PDGF and anti-VEGF phase 2 trial for wet AMD may have spurred Regeneron into moving quickly to begin two of its own combination studies. The trial Dr. Aberman was most likely referring to was conducted by Ophthotech.

Dr. Aberman said that although combination therapies for retinal disease appeared to be quite promising, he believes that drug combinations need to be “co-formulated” so as to minimize the number of injections that patients would need to receive.

The possibility of sustained-release implants for delivering anti-VEGF drugs has become a hot topic, but Dr. Aberman expressed rather broad reservations about the feasibility and safety of this type of delivery system. He said studies to date of implant devices “have not been that convincing that you’re really going to get much of a benefit in terms of duration with these devices.”

Dr. Aberman said Regeneron is looking forward to FDA approval of Eylea for DME as the company believes the opportunity could be as great as that for wet AMD therapies. He noted that patients with DME tend to be younger than those with wet AMD and would need drug therapy for a longer duration.

Finally, Dr. Aberman pointed to strong launches of Eylea in Australia and Japan, where Eylea has quickly taken about half of the branded anti-VEGF market it shares with Lucentis (ranibizumab). He said Eylea has achieved about equal market share with Lucentis in the overall branded marketplace and was being used more widely in “difficult” cases where it has demonstrated an ability to eliminate fluid more effectively than other anti-VEGF therapies. He said the development of Eylea had thus far cost Regeneron and international partner Baxter Healthcare approximately $1 billion.

Ophthotech Funded for Pivotal Fovista Trial

Management aligned for development phase.

■ Ophthotech Corp. has raised $175 million to finance a global phase 3 clinical program of its lead compound Fovista, an anti-platelet-derived growth factor (PDGF), in combination with anti-VEGF therapy for the treatment of wet AMD. The multi-national phase 3 trial is expected to begin in the third quarter of 2013 and enroll nearly 1,900 patients in more than 200 centers worldwide.

The financing consists of $125 million from Novo A/S, in exchange for royalties on Fovista sales. The remaining $50 million is in the form of a Series C preferred stock financing from Novo A/S and current venture investors in Ophthotech.

To accelerate the clinical development of Fovista, Ophthotech also announced the expansion of its management team. David R. Guyer, MD, the company’s chairman since its inception, has accepted the position of CEO, and Samir Patel, MD, co-founder and current president of Ophthotech, has been appointed to the additional role of vice chairman. Under the new management structure, Dr. Guyer will direct the company’s corporate and financial strategy, while Dr. Patel will focus fully on clinical development.

“We are grateful to our investors for their profound confidence in Ophthotech and Fovista as a potential game-changing therapy that we hope will improve outcomes for millions of people with wet AMD,” noted Dr. Guyer.

In a large, randomized, controlled phase 2b study reported last year, Fovista in combination with Lucentis (ranibizumab injection) demonstrated superior efficacy over Lucentis monotherapy in patients with wet AMD. Patients receiving the combination of Fovista (1.5 mg) and Lucentis gained a mean of 10.6 letters of vision on the ETDRS standardized chart at 24 weeks, compared to 6.5 letters for patients receiving Lucentis monotherapy, representing a 62% additional benefit. No significant safety issues were observed for either treatment group in the trial.

More Genetic Markers Linked to AMD

Seven new loci could lead to better predictive models.

BY RICH KIRKNER, EXECUTIVE EDITOR

■ The AMD Gene Consortium has identified seven new genetic loci that play a role in the pathogenesis of AMD and, with further research, may help to identify individuals at risk of developing more severe disease, according to a presentation before the Genetics Group at ARVO 2013.¹

Sudha K. Iyengar, PhD, of Case Western Reserve University School of Medicine, reported the discovery brings to 19 the total number of loci implicated in AMD. “The exact sizes of the seven new loci are smaller and some of them play a role on the same pathways that are involved with the 12 previously known loci,” Dr. Iyengar said. “Some on the other hand are completely new pathways that we know nothing about.”

The next step to applying these findings in the clinic is to identify how these loci function to cause the protein changes that set off the physiological cascade that leads to AMD. “From that we will be able to understand why some people perhaps get more severe disease, which has quite a bit of clinical application,” she said. When physicians and patients know of these markers, they will be better equipped to intervene earlier, with steps such as diet changes or smoking cessation, to avoid or prevent the onset of more serious disease, she added.

In an interview, Dr. Iyengar cited the 23andme DNA Spit Kit (23andme Inc., Mountain View, CA), the $99 home test that can identify up to 240 health conditions, as evidence that genetic testing is becoming more affordable and accessible. One of the challenges in using the genome to predict AMD, along with other eye diseases such as glaucoma and diabetic retinopathy, has been the weakness of their predictive models. “The new experiments that we are doing are going to give us better predictive models,” she said.

The AMD Gene Consortium, a network of international investigators representing 18 research groups, will continue to pursue that research. The report of the seven newly discovered loci was originally published online in the journal Nature Genetics.²

REFERENCES

1. Iyengar SK. Advances in the genetics of age-related macular degeneration. Presented at ARVO, Seattle, WA: May 5, 2013.

2. Fritsche LG, Chen W, Schu M, et al. Seven new loci associated with age-related macular degeneration. Nature Genetics. 2013;45:433-439.

Eylea Promising in New Indication

Positive data from myopic CNV study.

■ Regeneron Pharmaceuticals and Bayer HealthCare have announced positive top-line results for Eylea (aflibercept) Injection from the phase 3 MYRROR study in myopic choroidal neovascularization (mCNV).

In myopic CNV, abnormal blood vessels grow into the retina in severe myopes with refractive error in excess of -6.00 D. The disease is characterized by an abnormally elongated eye with a physical stretching of the sclera, choroid, and retina, resulting in degenerative and progressive changes. These changes can incite the development of choroidal neovascularization.

Myopic CNV has a poor prognosis and, if left untreated, can within approximately 10 years progress to legal blindness in a majority of patients. Most prevalent in east Asia, mCNV is the second most common cause of blindness in Japan.

In this trial, patients receiving Eylea at an initial dose of 2 mg, followed by treatment on an as-needed basis, had a mean improvement in best-corrected visual acuity (BCVA) from baseline at week 24 of 12.1 letters, compared to a loss of 2.0 letters in patients receiving sham injections.

“Effective treatment options are urgently needed for patients with myopic choroidal neovascularization (mCNV),” said Kemal Malik, MD, Bayer head of Global Development. “We are pleased that the results of this study demonstrate that Eylea may provide a treatment option for these patients.”

Data from this study will be presented at an upcoming medical conference. Bayer HealthCare expects to submit the first application for regulatory approval for this indication in Asia in the second half of 2013.

MYRROR was a double-masked, sham-controlled trial that randomized 122 patients to receive either Eylea 2 mg or sham. Patients in the active treatment arm received one initial 2 mg dose of Eylea. Patients were evaluated every four weeks and were eligible to receive additional Eylea 2 mg intravitreal injections on an as-needed basis, determined by visual and anatomic criteria, through 20 weeks.

Patients in the sham arm received monthly sham injections through week 20. Starting at week 24, patients in both arms were eligible to receive Eylea 2 mg on an as-needed basis through week 44. The primary endpoint of the study was the mean change at week 24 from baseline in BCVA as measured on the Early Treatment Diabetic Retinopathy Scale (ETDRS) eye chart, a standard chart used in research to measure visual acuity. RP

ERRATUM
In the article “Vitrectomy for DME Without Macular Traction” by Takao Hirano, MD, and Toshinori Murata, MD, PhD, in the June 2013 issue of Retinal Physician, Figure 1 on page 62 was incorrect. The correct figure appears below. Retinal Physician regrets the error.