Faricimab Data Confirm 16-Week Efficacy at 1 Year

A 6-mg dose shows no new safety concerns.

■ New data presented at the recent AAO meeting confirms earlier projections that a 6-mg dose of Genentech’s bispecific anti-VEGF/anti-Ang2 faricimab (formerly RG7716) delivered every 16 weeks can on average provide as good or better vision gains than Lucentis (ranibizumab; Genentech) administered every 4 weeks. The 1-year data were from Genentech’s phase 2 STAIRWAY study made up of 76 treatment-naïve patients with wet AMD.

Given the new STAIRWAY data, faricimab becomes the first investigational treatment for wet AMD to achieve confirmed 16-week dosing for the majority of patients in a clinical trial. The potential of more durable every 16-week dosing is considered important because other investigational drugs for wet AMD have recently shown efficacy at 12-week retreatment intervals, while Eylea (aflibercept; Regeneron) and Lucentis have been approved for 12-week dosing based on physician assessment.

“The STAIRWAY data show the potential of faricimab to allow fewer injections while achieving and sustaining the same visual gains seen with a current standard of care. Based on these data, we will be initiating a global phase 3 program for faricimab in wet AMD,” said Sandra Horning, MD, chief medical officer and head of Global Product Development in a news release.

Patients in the STAIRWAY study were treated with either faricimab 6 mg every 12 weeks or every 16 weeks, or ranibizumab 0.5 mg every 4 weeks. After 52 weeks, the average visual acuity gains for each treatment group were +11.4 letters with faricimab 16-week dosing, +10.1 letters with faricimab 12-week dosing, and +9.6 letters with ranibizumab 4-week dosing.

Among the treatment groups, the proportion of patients gaining more than 15 letters, the proportion of patients avoiding a loss of more than 15 letters, and reductions in central retina thickness were comparable. The rates of ocular and systemic adverse events observed with faricimab were similar to the rates observed with ranibizumab. No new safety signals were observed. The overall safety profile of faricimab appears consistent with the safety profile reported in patients with wet AMD who receive intravitreal anti-VEGF therapies.

Arshad Khanani, MD, MA, of Sierra Eye Associates in Reno, Nevada, who presented the STAIRWAY data, said the drug’s unique bispecific nature is a key advantage of the drug.

“The Ang2 inhibition offered by faricimab contributes to vascular stabilization and decreases microvascular inflammation,” he said.

Ocular Melanoma Therapy Promising at 1 Year

Aura Biosciences cites stable disease in trial.

■ Aura Biosciences, a developer of novel targeted therapies in ocular oncology, has said updated clinical data from its phase 1b/2 clinical trial evaluating the safety and efficacy of light-activated AU-011, the company’s lead product candidate for the primary treatment of choroidal melanoma, demonstrated encouraging results at the 1-year mark. This open-label, multicenter trial is designed to investigate single and multiple ascending doses of light-activated AU-011 in approximately 36 adult subjects with clinically diagnosed primary choroidal melanoma.

The data show that multiple administrations of AU-011 are well tolerated with no related serious adverse events, severe adverse events, or dose-limiting toxicities observed. Drug-related adverse events were all expected and included anterior-chamber inflammation, posterior-chamber inflammation, and increase in IOP, but all were manageable with standard-of-care treatments and resolved without clinical sequelae.

Treatment with AU-011 achieved preservation of BCVA with a mean change of -1.06 letters at 6 months and a mean change of -0.75 letters at 12 months. BCVA was preserved even in high-risk patients with tumors close to the fovea or the optic disk, a factor that typically correlates with a higher risk of irreversible severe vision loss following radioactive treatments. All patients achieved stable disease at the prespecified preliminary efficacy endpoint at 3 months. Biological activity has been confirmed with long-term tumor control in those patients with documented growth before treatment, reduction in tumor thickness, and localized inflammation around the tumor. An expansion cohort of the study is currently under way. The company plans to initiate a pivotal phase 3 clinical program following the phase 1b/2 study.

Eylea NPDR Trial Has Positive Results at 1 Year

New data will support approval application.

■ Regeneron’s phase 3, 402-patient PANORAMA trial evaluating Eylea (aflibercept) in patients with moderately severe and severe nonproliferative diabetic retinopathy (NPDR) met its 52-week primary endpoint and key secondary endpoints, the company announced. The new data will be added to previously released 24-week findings and used to buttress Regeneron’s application for approval of Eylea for NPDR, currently under review by the FDA.

On the primary endpoint at 1 year, 80% and 65% of patients receiving Eylea on an every 8- and every 16-week interval (after an initial monthly dosing period), respectively, experienced a 2-step or greater improvement from baseline on the Diabetic Retinopathy Severity Scale, compared to 15% of patients receiving sham injection. The 2 key secondary endpoints, which were reported for the first time and indicate the need for early intervention, achieved statistical significance based on the prespecified hierarchical analysis. Treatment with Eylea reduced vision-threatening complications (VTCs) by 82% to 85% and the development of center-involved diabetic macular edema (CI-DME) by 68% to 74% compared with sham injection.

The development of VTCs (proliferative diabetic retinopathy and anterior segment neovascularization) was 3% for the Eylea every 8-week group, 4% for the Eylea every 16-week group, and 20% for the sham injection group. CI-DME occurred in 8% of the Eylea every 8-week group, 7% of the Eylea every 16-week group, and 26% of the sham injection group. These events collectively occurred in 11% and 10% of patients receiving Eylea every 8 weeks or every 16 weeks, respectively, compared to 41% of patients receiving sham injection.

“In this trial of patients with diabetic eye disease and normal vision, it is notable that without treatment more than one third of patients developed a vision-threatening complication or diabetic macular edema within 1 year,” said George D. Yancopoulos, MD, PhD, president and chief scientific Officer of Regeneron, in a news release. “Eylea was able to reduce these complications by 68% to 85% even with every 4-month dosing, and moreover was able to reverse the anatomic severity of the disease. These results point to the potential value of earlier intervention in diabetic retinopathy.”

The average number of injections in the first year was 8.6 (of 9 planned) for the Eylea every-8-week group and 5.5 (of 6 planned) for the Eylea every-16-week group. Adverse events were consistent with the known profile of Eylea.

Brolucizumab Shows Continued Efficacy at Year 2

Additional data announced from phase 3 trials.

■ Novartis announced additional brolucizumab phase 3 results from year 2 (96 weeks) that reaffirmed its positive year 1 (48 weeks) findings from the large-scale HAWK and HARRIER trials. Brolucizumab met its primary endpoint of noninferiority versus aflibercept (Eylea; Regeneron) in BCVA and exhibited superiority in key retinal outcomes at year 1 while maintaining robust visual gains in year 2 in patients with wet AMD. These new 96-week data, based on prespecified secondary endpoints, were presented at the AAO 2018 annual meeting as a follow-up to year 1 data.

Relative to aflibercept, fewer brolucizumab 6 mg patients with wet AMD had intraretinal fluid and/or subretinal fluid at week 96 (24% for brolucizumab 6 mg vs 37% for aflibercept in HAWK and 24% vs 39% in HARRIER). Of the patients on brolucizumab 6 mg who successfully completed year 1 on a 12-week dosing interval, 82% in HAWK and 75% in HARRIER were maintained on a 12-week dosing interval in year 2. No new, previously unreported types of safety events were identified at week 96, and brolucizumab continued to be comparable to aflibercept with the overall incidence of adverse events balanced across all treatment groups in both studies.

According to Novartis, brolucizumab (RTH258) is a humanized single-chain antibody fragment and the most clinically advanced, humanized single-chain antibody fragment to reach this stage of development. The company says single-chain antibody fragments have characteristics such as small size, enhanced tissue penetration, rapid clearance from systemic circulation, and drug delivery characteristics. The proprietary innovative structure results in a small molecule (26 kDa) with potent inhibition of, and high affinity to, all VEGF-A isoforms.

Chinese Anti-VEGF Shows Good Durability

Conbercept may be a candidate for US approval.

■ Recently published data from the 114-patient, phase 3 PHOENIX trial in wet AMD shows that the anti-VEGF conbercept (Chengdu Kanghong Biotech), a recombinant fusion protein, provided a mean gain of almost 10 letters at 12 months with 12-week dosing. The data were published in the American Journal of Ophthalmology.

The conbercept group received intravitreal injections of conbercept (0.5 mg) once monthly for the first 3 months, then once quarterly until month 12. A sham group received first 3 monthly sham injections and then 3 monthly injections of conbercept (0.5 mg) followed by quarterly administrations until month 12. The primary endpoint was mean change from baseline in BCVA at month 3, which was +9.20 letters for the conbercept cohort and +2.02 letters for the sham group. The conbercept group also achieved a mean 79.2 micron reduction in central retinal thickness at 3 months.

At 12 months, the mean changes from baseline in BCVA letter score were +9.98 letters in the conbercept group and +8.81 letters in the sham group. The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage and increased IOP.

There has been much speculation in the retina community as to whether Chendu Kanghong plans to eventually file for US approval of conbercept, already approved for wet AMD in China. That will largely depend upon the results of the ongoing, 1,140-patient phase 3 PANDA study for treatment-naïve patients, which is scheduled to be completed in 2020. The PANDA study has 2 conbercept arms (0.5 mg and 1.0 mg) plus an Eylea (aflibercept; Regeneron) 2.0 mg arm as a comparator. In 2020, conbercept may face a crowded field of other durable potential competitors.

Orion Cortical Prosthesis System Now in Home Testing

Some users can sort laundry and identify curbs.

■ Second Sight Medical recently reported that 4 of 5 patients in its feasibility study of the company’s next-generation Orion Cortical Prosthesis System are now using the device at home and achieving some level of functional vision. The Orion attaches directly to the brain’s visual cortex, thus making it suitable to address almost any cause of blindness. Some of the patients in the feasibility study have shown that they are able to identify curbs, locate signs, locate a person in front of them, and/or distinguish light from dark laundry.

Second Sight President and CEO Will McGuire said the company is in the process of gathering data for the FDA on the device’s ability to provide functional vision for various tasks and improve the user’s quality of life. The data will be used as the basis for designing a 30-patient (or more) pivotal trial of the Orion.

In related news, the Centers for Medicare & Medicaid Services has finalized its Medicare hospital outpatient payment rate of $152,500 for the company’s first-generation Argus II Retinal Prosthesis System and the associated surgical implantation procedure for calendar year 2019. This is a significant increase from the $122,500 CMS allotted for the Argus II in 2018.

“We are delighted to have received CMS’ final 2019 outpatient payment rate, which provides Medicare patients continued access to our life changing technology,” said McGuire. “We are also happy to see the change in methodology that considers multiple years of historic data when setting a rate for a low volume device such as Argus. We believe this change will temper future year-to-year fluctuations in the reimbursement rate.”

In recent months, Second Sight has been primarily funded by company chairman Gregg Williams, but McGuire said Second Sight is now evaluating possible long-term financing options.