4D Molecular Therapeutics Reports Favorable 4D-150 Outcomes
4D Molecular Therapeutics announced positive interim data from the phase 2 PRISM clinical trial evaluating intravitreal 4D-150 in wet AMD patients with severe disease activity and a high treatment burden. The data, which included 24-week landmark results, were presented by Arshad M. Khanani, MD, MA, at the Angiogenesis, Exudation, and Degeneration 2024 Virtual Congress. Dr. Khanani reported that high dose 4D-150 resulted in an 89% reduction in the annualized anti-VEGF injection rate; 84% of patients received 0 or 1 injection; 63% were injection-free through 24 weeks; and VA and CST were both stable vs aflibercept.
“Results from the phase 1 and interim results from phase 2 cohorts of the PRISM study confirm that 4D-150 is well tolerated and maintains stable visual acuity in previously treated high-need patients. 4D-150 also significantly reduces treatment burden while effectively controlling disease activity without fluid fluctuations,” Dr. Khanani, Sierra Eye Associates, Reno, Nevada, said in a news release.
Adverum Announces Positive Preliminary Data From Ixo-vec in Wet AMD
Adverum Biotechnologies announced preliminary safety and efficacy data from the ongoing LUNA phase 2 trial in patients with wet AMD, at the annual meeting of the Macula Society. The presentation revealed that both the 2E11 and 6E10 doses of Ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy demonstrated maintenance of visual and anatomic outcomes, and Ozurdex (AbbVie) plus difluprednate was identified as a potential “go-forward” prophylaxis. Most patients on the “go-forward” regimen had no inflammation and greater than 90% of patients had no or minimal inflammation. Notably, both doses resulted in a potentially best-in-class reduction in annual VEGF injections, with data trending similar to or better than the OPTIC study, in which patients continued to see clinical benefit through 3 years.
“These results were seen in hard-to-treat patients, who received over 9 injections in the year prior to receiving Ixo-vec,” Laurent Fischer, MD, president and CEO of Adverum Biotechnologies, said in a news release.
Bausch + Lomb Presents Xipere Data at Macula Society Meeting
Bausch + Lomb presented findings from a study assessing the durability of Xipere and subsequent patterns for treatment of uveitic macular edema in clinical practice, at the annual Macula Society Meeting. Xipere is the first and only treatment to be approved in the United States for delivery via the suprachoroidal space and the first and only uveitic macular edema treatment to demonstrate clinical efficacy with a BCVA primary endpoint.
“Overall, 24.6% of patients required a corticosteroid in the 24 weeks after suprachoroidal triamcinolone acetonide. By comparison, rescue therapy was required by 13.5% of patients in the clinical trial despite the use of a second suprachoroidal triamcinolone acetonide injection at week 12 that was not counted as rescue. A second injection around week 12 does not appear to be part of routine clinal practice as only 2.4% of eyes had an injection in that timeframe,” Bausch + Lomb reported in a news release.
Exonate Successfully Completes Phase 1b/2a Trial in DME
Exonate announced that it has achieved its prespecified endpoints in a phase 1b/2a study of EXN407 for DME. During the trial, EXN407, which is a small molecule inhibitor of splice factor kinase SRPK1, met all safety and pharmacokinetic parameters and displayed encouraging signals of biologic activity. Patients were treated twice a day for 3 months, with either EXN407 or placebo. Study results included: no clinically meaningful changes in any safety parameters; no reported tolerability issues; and no adverse events leading to treatment or study discontinuation.
“The results from the EXN407 trial are very encouraging, with the data validating the hypothesis that modulating VEGF splicing can lead to clinical benefits. We are excited to progress to the phase 2 trial next year and welcome inquiries by potential partners for the program,” Catherine Beech, Exonate CEO, said in a news release.
Preliminary Real-world Data on Faricimab Presented
Preliminary data from VOYAGER, a noninterventional, prospective, multinational, multicenter study designed to evaluate real-world effectiveness of faricimab in patients with neovascular AMD and DME, were presented at the Angiogenesis, Exudation, and Degeneration 2024 Virtual Congress. Data were reported for 220 eyes of 174 patients with nAMD and 107 eyes of 69 patients with DME. The preliminary data show that visual acuity increased from baseline to month 3 in nAMD and DME patients who switched to faricimab from ranibizumab, aflibercept, brolucizumab, or other anti-VEGFs, upon enrollment in VOYAGER. Another important preliminary finding indicates that CST decreased rapidly from baseline to month 3 in both nAMD and DME patients who switched to faricimab from other VEGFs, upon study enrollment. Investigator tolerance of fluid was disease-dependent and treat-and-extend regimens were preferred, according to the interim analysis. The preliminary data were from sites in the United States, Canada, and Japan.
Opthea Completes Enrollment in First Pivotal Trial of Sozinibercept
Opthea announced that it has completed enrollment of all patients in the COAST phase 3 pivotal clinical trial investigating sozinibercept (OPT-302) in combination with aflibercept anti-VEGF-A therapy, for the treatment of wet AMD. Sozinibercept is a soluble form of VEGFR-3 that binds and neutralizes the activity of VEGF-C and VEGF-D. The sozinibercept clinical program includes 2 phase 3 pivotal trials, COAST and ShORe.
“We believe sozinibercept has the potential to provide superior clinical results, based on the strength of our phase 2b trial, which demonstrated a statistically significant improvement in visual acuity for patients treated with sozinibercept combined with Lucentis (ranibizumab) compared to ranibizumab alone,” Frederic Guerard, Opthea CEO said in a news release. Enrollment in ShORe is expected to be completed in Q2 2024. Opthea intends to report top-line results from these 2 trials by mid-2025.
Sandoz Acquisition of Cimerli From Coherus Strengthens Eye-care Portfolio
Sandoz announced that it has signed an agreement to acquire the US biosimilar ranibizumab Cimerli (ranibizumab-eqrn) from Coherus BioSciences, for an upfront cash purchase payment of $170 million. This includes a biologics license application, product inventory, ophthalmology sales and field reimbursement talent, and access to proprietary commercial software. The agreement to acquire the Cimerli business from Coherus allows Sandoz to build a more robust ophthalmic platform capable of supporting future product launches. Closing is anticipated in the first half of 2024.
Keren Haruvi, president, Sandoz North America, said in a news release, “I am pleased that we can add another high-value product to the growing Sandoz biosimilar portfolio, further strengthening our existing ophthalmology franchise. The addition of Cimerli reinforces our commitment to biosimilars and represents a huge step towards our goal of pioneering patient access to more affordable and much-needed medicines in the United States.”
Retinal Structure Improvements Seen in OpRegen RPE GA Study
Results from the phase 1/2a clinical study of Lineage Cell Therapeutics’ RG6501 (OpRegen), in GA secondary to advanced AMD, were presented at the Angiogenesis, Exudation, and Degeneration 2024 Virtual Congress, by Allen Ho, MD, Wills Eye Hospital, Philadelphia. Dr. Ho reported that following subretinal administration of OpRegen, all patients with extensive delivery to GA showed improvement in outer retinal structure on quantitative OCT analysis by a masked grader. Other key findings include: anatomic improvement correlated with greater gains in BCVA, and it was detectable within 3 months of administration; the extent of OpRegen bleb coverage may be important to optimize patient outcomes; and time of onset may be influenced by postoperative changes and interpatient variability. The findings suggest that OpRegen RPE cells may counteract RPE cell dysfunction and loss in GA by providing support to the remaining retinal cells within atrophic areas, according to Dr. Ho.
Some Wet AMD Patients Respond Better to Faricimab Than Anti-VEGF Only
In a study designed to investigate the effect of switching neovascular AMD patients from various anti-VEGF therapies to the novel, bispecific agent faricimab (Vabysmo; Genentech), researchers from Cleveland Clinic’s Cole Eye Institute found that switching to intravitreal faricimab injections resulted in stable vision and a significant improvement in macular OCT parameters. One hundred twenty-six eyes of 106 patients were included in the analysis. Before the transition to faricimab, patients received either aflibercept, bevacizumab, ranibizumab, or brolucizumab injections. The most common agent used before switching to faricimab was aflibercept. Switching to faricimab resulted in a reduction in mean CST (-11.6 μm, P=.01) and PED height (-44.2 μm, P=.01) after 3 injections, with stable VA and at a similar treatment interval to prior anti-VEGF therapy. The outcomes suggest that patients who have a suboptimal response to the anti-VEGF therapies could potentially benefit from switching to faricimab.
Home OCT Monitoring May Help in Management of Wet AMD
Home OCT monitoring has the potential to provide clinically meaningful and dense data to complement clinical management of patients with wet AMD, according to a study facilitated by Michael Elman, MD, from Elman Retina Group in Philadelphia. The study revealed that treatment decisions made by retina specialists who had access to nAMD patients’ home OCT data differed substantially from decisions made by retina specialists who did not have access to the home OCT data. Fifteen retina specialists reviewed 150 home OCT data segments from 29 patients with nAMD. They were asked to make decisions about when to offer treatments and treatment types. They were also asked to set the retinal fluid and time thresholds for notification. Based on home OCT data, they decided not to treat in 64 cases (42.7%). In actual clinical care, the patients were all treated on the last day. Out of the remaining 88 cases, they decided to treat earlier than in actual clinical care in 87 cases.
First Phase 1 Study Results of Kodiak’s Bispecific KSI-501ABC Reported
The first results from Kodiak Sciences’ phase 1 multiple ascending dose study of KSI-501ABC in patients with DME were presented at the Angiogenesis, Exudation, and Degeneration 2024 Virtual Congress, by Mark R. Barakat, MD, of Retina Macula Institute of Arizona. The study enrolled treatment-naïve and previously treated DME patients with an 8-week washout period. Study patients received 3 monthly doses and were followed for 24 weeks. Dr. Barakat reported that repeated monthly dosing of KSI-501 was safe and well tolerated. Bioactivity was demonstrated in both functional BCVA and anatomic OCT and CST measures, and meaningful and sustained gains in BCVA were achieved. KSI-501 is designed to inhibit both IL-6 mediated inflammation and VEGF-mediated angiogenesis and vascular permeability. It is being developed as KSI-501ABC (antibody biopolymer conjugate) for the treatment of high-prevalence retinal vascular diseases, and KSI-501P, its unconjugated bispecific protein, for the treatment of macular edema secondary to inflammation.
In Brief
Ascidian Therapeutics announced that the FDA has cleared its investigational new drug (IND) application and granted Fast Track designation for ACDN-01, the first clinical-stage RNA exon editor and the only clinical-stage therapeutic targeting the genetic cause of Stargardt disease. Ascidian expects to initiate enrollment in the phase 1/2 STELLAR study, which will evaluate the safety and efficacy of a single dose of ACDN-01 administered via subretinal injection in individuals with Stargardt disease and other ABCA4 retinopathies, in the first half of 2024.
Ikerian AG and RetinAI announced that they have launched the Discovery for Clinics practice management program for ophthalmologists and optometrists. The platform aggregates and connects large data sets on a single, cloud-based repository. The data are then automatically analyzed with RetinAI’s CE-marked and Research Use Only (RUO) artificial intelligence (AI) algorithms for accelerated and AI-biomarker–based treatment decisions.
Ocular Therapeutix announced that the FDA has agreed to a Special Protocol Assessment (SPA) Agreement Modification for the company’s pivotal phase 3 SOL clinical trial of the axitinib intravitreal implant, also known as OTX-TKI, for the treatment of wet AMD. The amendment expands the eligibility criteria for the SOL trial, such as including treatment-naïve wet AMD subjects with VA of approximately 20/80 or better at the initial screening visit. Broadening of eligibility criteria is expected to accelerate overall trial enrollment.
Nanoscope Therapeutics provided an update following regulatory discussions with the FDA and the Icelandic Medicines Agency (IMA), regarding the regulatory path of MCO-010 for the treatment of retinitis pigmentosa. Based on these discussions, Nanoscope announced that it has reverted to VA as the primary endpoint in RESTORE, the ongoing randomized, double-masked, multicenter phase 2b study of MCO-010.
Ophthalmologists at New York Eye and Ear Infirmary of Mount Sinai (NYEE) have created a novel protocol to rapidly diagnose eye stroke and expedite care to prevent irreversible vision loss. Their study, published in Ophthalmology, describes using high-resolution retinal imaging in the emergency room, along with rapid remote consultation to confirm diagnosis and expedite care, improving outcomes for eye stroke patients and preserving vision.
Kiora Pharmaceuticals announced that it has entered a strategic agreement with Théa Open Innovation (TOI) that grants TOI exclusive worldwide development and commercialization rights (excluding Asia) to KIO-301 for the treatment of degenerative retinal diseases. In exchange, Kiora will receive an upfront, payment of $16 million and up to $285 million upon achievement of prespecified clinical development, among other things.
The first patient has been dosed in a phase 1 study of one of the novel therapeutics being developed by Inflammasome Therapeutics for the treatment of DME. The 24-week study is designed to assess safety and initial evidence of efficacy of a dual inflammasome inhibitor, K-8, that targets inflammasome activation in the eye believed to be associated with DME. The K-8 will be delivered via sustained-release implant. Primary outcome measurements include mean change in CST from baseline, and mean change in BCVA. The study will enroll 5 patients and is expected to be completed this year.
