Eylea Maintains Vision Gains in DME
Two-year data show stable BCVA.
■ Regeneron Pharmaceuticals and Bayer HealthCare have released two-year data from the pivotal phase 3 VISTA-DME trial indicating that aflibercept (Eyelea) sustained significant vision gains through the second year of treatment when compared with laser photocoagulation. Regeneron has filed a submission with the FDA requesting approval of Eylea for the DME indication, and estimates that the DME market opportunity could eventually be as large as that of wet AMD, for which Eylea is already approved.
Patients in the VISTA-DME trial were randomized to receive either 2 mg of Eylea monthly (n=155), 2 mg of Eylea every eight weeks (n=152), or laser photocoagulation (n=154).
After two years, patients receiving Eylea monthly had a mean change from baseline in BCVA of 11.5 letters (12.5 letters at 52 weeks). Patients receiving Eylea every eight weeks had a mean change from baseline in BCVA of 11.1 letters (10.7 letters at 52 weeks). Patients in the laser photocoagulation treatment group had a mean change from baseline in BCVA of 0.9 letters (0.2 letters at 52 weeks).
“These data showed that treatment with Eylea in this trial improved vision and maintained the improvement over two years in patients with diabetic macular edema,” says George D. Yancopoulos, MD, PhD, chief scientific officer of Regeneron. “These results are particularly encouraging given that 43% of patients in this study had previously received anti-VEGF therapy.”
In other Regeneron news, the company said the FDA has accepted for standard review its application for the approval of Eylea to treat macula edema following branch retinal vein occlusion. The submission is based on positive data from the ongoing phase 3 VIBRANT trial.
The company also reported that full-year 2013 US sales of Eylea were $1.41 billion compared to $838 million for the previous year. The company projected full-year 2014 US sales of Eylea at $1.7 to $1.8 billion. A market research survey commissioned by Regeneron indicated that Eylea and Lucentis (Genentech) are now sharing the US market for branded wet AMD drugs almost equally.
■ Aerpio begins DME study using subcutaneous self-administration. Aerpio Therapeutics, Cincinnati, OH, a clinical-stage biopharmaceutical company, has dosed the first patient in a phase 2 trial evaluating AKB-9778, a Tie2 activator, alone and in combination with ranibizumab (Lucentis) for the treatment of DME.
AKB-9778 is an inhibitor of human protein tyrosine phosphatase beta (HPTP-beta) that activates the Tie2 pathway to promote vascular stability, preventing abnormal blood vessel growth and vascular leak. Patients self-administer AKB-9778 subcutaneously.
In a previously reported phase 1b/2a study in patients with DME, Aerpio said AKB-9778 administered subcutaneously as monotherapy over 28 days was well tolerated and produced clinically meaningful reductions in retinal thickness, which correlated with improved visual acuity.
“Emerging preclinical and clinical data indicate that the Angiopoietin/Tie2 pathway is a major axis for maintenance and stabilization of retinal blood vessels,” says Kevin Peters, MD, chief scientific officer, Aerpio. “Results in preclinical models and in our phase 1b study indicate that AKB-9778 has great promise as monotherapy in both treatment-naïve and treatment-resistant DME patients. In addition, since Tie2 activation is complementary to the action of anti-VEGF agents, the current standard of care for patients with DME, AKB-9778 could also represent a major advance as an adjunct to anti-VEGF therapy.”
The randomized, double-masked, double-dummy, phase 2 study is designed to assess the safety and efficacy of AKB-9778 administered over three months as monotherapy and as an adjunct with ranibizumab in subjects with DME. The primary study endpoints are change from baseline in visual acuity and central retinal thickness in the groups treated with AKB-9778 monotherapy and AKB-9778 as an adjunct with ranibizumab, compared to ranibizumab monotherapy. The study will enroll approximately 120 subjects (40 patients in each of three groups) at approximately 35 sites.
Case Study: Eyedrop Combats PDR
Initial data on squalamine is encouraging
■ Ohr Pharmaceutical (New York, NY) said a case report on the first patient treated in an ongoing investigator-sponsored trial with squalamine eyedrops in proliferative diabetic retinopathy (PDR) demonstrated promising results.
Self-administration of squalamine eyedrops two and then four times daily was able to induce regression of neovasculature of the patient, according to Ohr. Visual acuity did not change in a patient who was 20/25 at baseline. Trial investigator Michael J. Elman, MD, director of the Elman Retina Group in Baltimore, MD, presented the results last month at the 37th Annual Macula Society meeting in Key Largo, FL.
The concept of an eyedrop reaching the back of the eye and delivering a drug at therapeutic levels has both its supporters and detractors, because topical administration has so far not proved effective for back-of-the-eye diseases. Ohr has attracted a number of prominent retina specialists to its scientific advisory board who have viewed the current clinical studies of squalamine with interest.
Dr. Elman’s oral presentation discussed the case of a treatment-naïve patient diagnosed with PDR. The data demonstrated that topical application of squalamine eyedrops in a monotherapy regimen, BID and then QID, was associated with regression of retinal neovascularization within two months. The retinal neovascularization remained regressed throughout the six months of QID squalamine drop therapy.
DISEASE RETURNS AFTER TREATMENT STOPPED
One month after cessation of squalamine treatment, the abnormal blood vessels returned in this patient’s retina, and continued to grow through month two, the furthest time point measured.
“These are promising results which provide the first evidence in a human eye that topical application of squalamine can produce a biological effect in retinal disease,” said Dr. Elman. “This regression of these vision-threatening blood vessels while on topical squalamine treatment, coupled with the return and worsening of the neovascularization once squalamine was stopped, supports a therapeutic treatment response of the neovascularization to topical squalamine drops when used as monotherapy.”
Irach Taraporewala, CEO of Ohr Pharmaceutical, also commented, “We are encouraged by the early data observed in Dr. Elman’s case report from a single patient and look forward to seeing further results once the trial is complete. There is a clear unmet medical need for topical therapies to treat back-of-the-eye diseases. We look forward to the interim data from the ongoing phase 2 wet-AMD clinical trial in the second quarter of 2014. The company continues to expand the squalamine eye drop clinical programs and we expect to have two additional investigator-sponsored trials initiated in diabetic macular edema during the current quarter.”
Dr. Elman’s ongoing five-patient OHR-003 trial is designed to determine the efficacy of topical 0.2% squalamine lactate ophthalmic solution in the treatment of retinal neovascularization resulting from proliferative diabetic retinopathy. The endpoints include regression of neovascularization, anatomical measurements, visual acuity, and safety parameters.
■ Ophthotech receives $41.7 million in new funding. Ophthotech Corporation (New York, NY), which is developing a combination therapy for the treatment of retinal disease, has received approximately $41.7 million in financing from Novo A/S.
The second payment was triggered when Ophthotech reached an initial enrollment milestone of a specified number of patients in its pivotal, multinational phase 3 clinical program of Fovista, Ophthotech’s anti-platelet-derived growth factor (PDGF) compound being studied in combination with anti-VEGF therapy for the treatment of wet AMD. Ophthotech initiated patient enrollment in the phase 3 clinical program of Fovista last August and continues to expect to have initial top-line data in 2016.
In addition, Ophthotech has conducted a public offering of 1.9 million shares of company common stock at a price of $31.50 per share. The proceeds will be used to fund clinical trials and for general business purposes.
Fellows’ Forum: A Fast-paced Learning Experience
Numerous timely topics covered in two days.
■ The 14th annual Retina Fellows’ Forum took place on January 24 and 25 in Chicago, IL. Eighty-three North American vitreoretinal fellows participated in an educational and social program that has become a much-anticipated fixture of the final year of vitreoretinal training.
As in past years, the fellows spent considerable time in the lecture hall with a faculty led by David Chow, MD, course director, and co-directors Carl Awh, MD, and Tarek Hassan, MD. Drs. Maria Berrocal, Dean Eliott, Phil Ferrone, Mike Jumper, and Jon Prenner completed the faculty lineup.
The meeting began with an AMD Symposium and sessions on ocriplasmin (Jetrea, ThromboGenics, Leuven, Belgium) for symptomatic vitreomacular traction and on pediatric retina. Controversies in the management of AMD, including recent advances in genetic testing for AMD, and AREDS supplements, made for lively discussion.
The Friday evening reception and dinner provided the first opportunity for the graduating class of 2014 fellows to socialize with their peers, the faculty, and industry representatives.
DR. YALE FISHER DELIVERS GUEST LECTURE
Saturday offered a full day of panel discussions on diabetic retinopathy, retinal vascular occlusion, trauma, macular surgery, complex diabetic vitrectomy, and new devices. Yale Fisher, MD, of Bascom Palmer Eye Institute, Miami, FL, and founder of OphthalmicEdge.org, presented the Distinguished Guest Lecture.
Dr. Fisher described how a simple misunderstanding during a fellowship interview impacted his life and career. The afternoon concluded with a “Real World” panel discussion on career and life decisions.
The Retina Fellows’ Forum Research award went to Christopher Brady, MD, of Wills Eye Institute, Philadelphia, PA, for his paper, “Rapid grading of fundus photos for diabetic retinopathy using crowd sourcing.” Dr. Brady will present the paper at the American Society of Retina Specialists annual meeting August 9 to 13 in San Diego, CA, as a recognized lecture.
The Fellows’ Forum concluded with dinner, an informal awards ceremony, and the ninth annual Retina Fellows’ Forum Bowling Tournament. The 15th Annual Retina Fellows’ Forum will be held in Chicago on January 30 and 31, 2015.
Genentech was the major corporate supporter of the Retina Fellows’ Forum. Seventeen additional companies representing a cross-section of devices and services important to vitreoretinal practice provided financial support and presented updates to the group about their businesses.
■ PRN dosing maintains Lucentis vision gains in DME. Patients completing the three-year RIDE/RISE phase 3 clinical trials were given the option of continuing to receive 0.5 mg doses of ranibizumab (Lucentis) on a PRN basis in an open-label extension (OLE) trial. Of the 335 patients who had received monthly ranibizumab during RIDE/RISE and who continued into the OLE, most were able to maintain their vision gains with a mean of 4.5 retreatments over an average 14.1-month follow-up period. Twenty-five percent of the patients in the OLE required no retreatments at all during the follow-up period.
These data were reported by researchers led by Lawrence S. Morse, MD, PhD, of the University of California-Davis at the annual Macula Society meeting in February.
The researchers found that, on average, the 165 patients who had received sham injections during RIDE/RISE and who received ranibizumab in the OLE were never able to catch up to the mean 15+ letter vision gains achieved by patients who had received ranibizumab from the start.
■ Iluvien gets limited approval in Scotland. Alimera Sciences said that the Scottish Medicines Consortium has accepted the company’s Iluvien sustained-release implant for DME for restricted use within the National Health Service (NHS) Scotland.
The approval provides patients considered insufficiently responsive to available therapies with access to Iluvien, the only sustained-release treatment for chronic diabetic macular edema. The approval is restricted to treatment of pseudophakic eyes. RP