Eylea Has Positive BRVO Trial
Regeneron also studies sarilumab for uveitis.
BY JERRY HELZNER, SENIOR EDITOR
■ Regeneron Pharmaceuticals, based in Tarrytown, NY, has announced positive top-line results for aflibercept (Eylea) from the phase 3 VIBRANT study in patients with macular edema following branch retinal vein occlusion (BRVO). In this trial, 53% of patients who received Eylea 2 mg every four weeks gained at least 15 letters in vision from baseline at week 24, the primary endpoint of the study, compared to 27% of patients who received laser, a standard-of-care treatment.
In addition, Regeneron recently initiated a 57-patient, 16-week clinical trial for the monoclonal antibody sarilumab for the treatment of non-infectious uveitis. Investigators will administer the drug subcutaneously every two weeks for patients with noninfectious intermediate, posterior or panuveitis. The primary endpoint will be at least a two-step reduction in vitreous haze or a significant reduction in prednisone dosing to less than 10 mg per day. Regeneron is also studying sarilumab for the treatment of rheumatoid arthritis.
In the BRVO trial, the incidence of serious adverse events (SAEs) was 9.9% in the Eylea group and 9.8% in the laser group. One death and one non-fatal stroke occurred during the trial, both in patients in the laser group. The most common ocular adverse events in the Eylea-treated patients were conjunctival hemorrhage and eye pain. No cases of intraocular inflammation occurred. The one ocular SAE in a patient in the Eylea group was a traumatic cataract.
“These positive data in patients with macular edema following BRVO further support the efficacy of Eylea in a broad spectrum of retinal diseases,” said George D. Yancopoulos, MD, PhD, Regeneron’s chief scientific officer. “If approved, we hope to be able to offer physicians and patients a new treatment option for addressing macular edema associated with this severe and potentially blinding form of retinal disorder.”
“VIBRANT represents the eighth positive trial from the Eylea phase 3 program, which has enrolled over 3,800 patients from around the world,” said Robert Vitti, MD, vice president, clinical sciences, ophthalmology.
Detailed results from this study will be presented at an upcoming medical conference. Regeneron intends to submit a regulatory application for marketing approval for macular edema following BRVO in the United States within the next several months.
■ Eylea accepted for DME review. Regeneron reported the FDA has accepted its supplemental Biologics License Application (BLA) for the review of aflibercept (Eylea) for the treatment of DME. The FDA has granted a standard review period of 10 months from the BLA submission, with possible approval for the indication as early as August 2014.
Eylea has already been approved by the FDA for the treatment of both wet AMD and macular edema associated with central retinal vein occlusion.
■ Ampio to continue DME trial. Ampio Pharmaceuticals (Greenwood Village, CO) said an Independent Data Review Committee (IDRC) made up of a statistician and a retina specialist had reviewed the available four-week results of its planned 12-week phase 2b trial of oral danazol (Optina) as a treatment for DME and found evidence of a “potentially beneficial anatomic effect” with no significant safety concerns.
The four-week data encompassed approximately 30% of the 250 patients currently enrolled in the trial. Ampio said the IDRC finding meant that the trial would continue as planned.
Because danazol is already approved for endometriosis, the company believes it has a shorter path to approval if the clinical trial data shows efficacy.
■ Synergetics USA reports sales increase. Synergetics USA, (O’Fallon, MO) which manufactures instruments and devices used in vitreoretinal surgery, recorded sales of $15.5 million in the first quarter of fiscal 2014, representing a 6.2% increase over the comparable quarter a year ago. The increase was driven by a 13% rise in disposable product sales and growing demand for the company’s VersaVIT portable vitrectomy machine.
QLT Begins Trial for IDA Treatment
Oral retinoid studied to restore visual sensitivity.
■ QLT, Inc., (Vancouver, BC) has dosed the first patient in the company’s phase 2a trial of its oral retinoid 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.
QLT has ended or sold off all of its other initiatives to focus solely on its oral retinoid program, which also encompasses therapies for Leber’s congenital amaurosis and retinitis pigmentosa.
The IDA trial is a randomized, multi-center, parallel-group, placebo-controlled study in 40 adults with IDA. Subjects age 60 or older with IDA, or impaired low-luminance low-contrast BCVA (“LLLC BCVA”) in at least one eye and having no known ophthalmic pathologies to explain their condition, other than early-stage AMD, will be enrolled at sites in the United States.
Subjects are being randomized to receive placebo or one of two different doses (10 or 40 mg/m2) of QLT091001 once a week for three consecutive weeks with one additional dose the day after the third dose. The trial is designed to evaluate the safety profile and effects of the drug on impaired dark adaptation time, glare recovery time and LLLC BCVA.
“We are pleased that dosing of the first patient has occurred on schedule, marking another significant milestone for QLT in the advancement of our synthetic oral retinoid program in multiple indications,” said Jason M. Aryeh, chairman of the board. “This is an important step outside of rare orphan diseases with QLT091001, one which is designed to illustrate its potential in a significantly larger patient population.
IDA is a condition that results in decreased ability of the eye to recover visual sensitivity in the dark following exposure to bright lights (photo-bleaching) that gets worse with age. Profoundly impaired dark adaptation is commonly associated with inherited retinal degenerations. More recently, mild to moderate impaired dark adaptation has been proven to be associated with AMD and proportional to the severity of the disease.
IDA may occur due to age-related inefficiencies in the retinoid cycle, resulting in slower regeneration of the light-sensing pigment 11-cis-retinal in the eye and increased levels of free unbound opsin that lead to delayed dark adaptation and reduced retinal sensitivity.
Ultimately, these factors impair vision in low light or dark environments. The kinetics of the rod function have also been reported to be age-related, with the rod-mediated portion of the dark adaptation function significantly slower in older patients with normal retinal function than in younger adults. This rod-mediated dark adaptation time is further slowed down in patients with early signs of AMD but with good visual acuity.
IDA in this population causes symptomatic difficulties for functioning in dim light, especially after exposure to bright ambient light, and can hamper daily living activities such as driving, mobility and workplace tasks. IDA is not a disease but a condition that can arise as a result of a number of pathologic or physiologic factors.
Improving this condition has the potential to not only improve a subject’s quality of life but also delay the development of degenerative retinal conditions that carry worse visual outcomes.
■ Haag-Streit offers Sony 3D video. Haag-Streit USA (Mason, Ohio) now offers Sony Electronics’ medical-grade 3D video camera, video recorder, and displays with Haag-Streit’s line of surgical microscopes.
The company says the high-definition, medically compliant equipment is designed to enable surgeons and clinicians to capture, record and display 3D video in the operating room, providing the ability to share the procedure in 3D in both real time and for playback later.
■ Stem cells in dry AMD trial. Bioheart, Inc., (Sunrise, FL) will enroll patients in a study of stem cell therapy for dry AMD. The study will enroll up to 100 patients to determine the safety and efficacy of adipose-derived stem cells (AdipoCell.)
Specific Biomarker Makes GA Drug More Effective
Patients with complement factor I more responsive.
■ With no approved therapies for geographic atrophy, the advanced form of dry AMD, newly released details of Genentech’s (Roche, South San Francisco, CA) phase 2 MAHALO study indicate that identifying specific patient biomarkers may play a role in developing effective treatments for this disease.
In the MAHALO trial, using genotype samples, 53 of 93 patients tested positive for the complement factor I biomarker (CFI).
In the subgroup of patients who tested positive for CFI and also received monthly injections of the drug lampalizumab, data showed a 44% decrease in disease progression at 18 months. Patients who received drug injections every other month showed an 18% decrease in progression at 18 months.
Roche concluded that “the strongest treatment effect was observed in patients positive for the Complement Factor I genetic biomarker.”
All patients in the study were tested for four genetic biomarkers: complement factor H (CFH), C3, C2/CFBs and CFI.
“These preliminary biomarker data could help identify patients most likely to respond to treatment with lampalizumab,” said Richard Scheller, PhD, head of research and early development for Genentech.
Noting that AMD has a strong genetic component, with genetic factors accounting for a major part of the risk for the disease, Roche said Genentech will continue to investigate the biomarker strategy to determine which patients would benefit most from genotyping for specific bio-markers.
■ Alimera Sciences to discuss Iluvien labeling with FDA. After several failed attempts, It now appears that new hope exists for FDA approval of Iluvien, Alimera Science’s long-duration implant for the treatment of chronic DME.
Alimera (Alpharetta, GA) has begun labeling discussions with the FDA for Iluvien and, as a result, reached an agreement with the FDA that Alimera’s participation in the January Dermatologic and Ophthalmic Advisory Committee meeting was not necessary. Alimera will focus instead on drafting its response to the Complete Response Letter (CRL) the FDA issued in October 2013, with a goal of submitting the response in the first quarter of this year.
In its response, Alimera intends to address concerns the FDA raised regarding the facility at which Iluvien is manufactured. In addition, Alimera expects to provide a safety update on Iluvien, which will include data from Iluvien patients and from physician experience with the applicator in the United Kingdom and Germany, where Iluvien is currently commercially available. The FDA has indicated that Alimera will not be required to conduct any new clinical trials in connection with the FDA’s review of Iluvien prior to approval.
“We are committed to addressing the remaining issues that were raised in the CRL and plan to submit our response in the first quarter of 2014, which will include recent safety data gathered from our patients in Europe,” said Dan Myers, president and CEO of Alimera.
■ Jetrea given a CMS J-Code. CMS has published the permanent HCPCS (Healthcare Common Procedure Coding System) code for ocriplasmin (Jetrea, ThromboGenics, Iselin, NJ). The code is J7316. The permanent J-Code for Jetrea became effective January 1.
Prior to the granting of the permanent J-Code, US physicians had to manually submit Jetrea claims to payers following their use of this first medical treatment for symptomatic vitreomacular adhesion. This led to delays in reimbursement, ThroboGenics says the permanent J-Code will streamline the reimbursement process and instill higher reimbursement confidence.
The company said lack of a J Code had been affecting Jetrea sales.
In other ThromboGenics news, company founder Désiré Collen, MD, PhD, has retired as chair and board member. Staf Van Reet, PhD, a member of the ThromboGenics board with a long career in the field of biopharma, has been appointed chairman of the company. RP