Rose Bengal Electromagnetic Activation with Green light for Infection Reduction II (REAGIR II) is a randomized, double-masked feasibility study. The purpose of this study is to determine differences in 6-month visual acuity between medical antimicrobial treatments alone versus antimicrobial treatment plus cross-linking with rose Bengal (RB-PDT).
Patients presenting to one of the Aravind Eye Hospitals in India or to the Federal University of São Paulo ophthalmology clinic in Brazil with smear-positive and/or culture positive typical (I.e. non-Nocardia or Mycobacteria) bacterial corneal ulcers and moderate to severe vision loss, defined as Snellen visual acuity of 20/40 of worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of two treatment groups:
Group 6, RB-PDT Plus Early Steroids: topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus RB-PDT
Group 7, Sham RB-PDT Plus Early Steroids: topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus sham RB-PDT

Start Date30 Apr 2024

Sponsor / Collaborator

The University of California, San Francisco

[+3]

NCT05649111 / RecruitingPhase 4IIT

A Study of the Effect of Different Doses of Difluprednate Eye Drops on the Intraocular Pressure After Phacoemulsification

The study aims at detecting the minimum effective daily dose and duration of difluprednate that can be used to treat postoperative inflammation after phacoemulsification without increasing the intraocular pressure, and whether it can be safely given within the first 24 hours after the operation.

Start Date01 Nov 2022

Sponsor / Collaborator

Kafrelsheikh University

NCT04097730 / Active, not recruitingPhase 3IIT

Steroids and Cross-linking for Ulcer Treatment

Steroids and Cross-linking for Ulcer Treatment (SCUT II) is an international, randomized, double-masked, clinical trial. The purpose of this study is to determine differences in 6-month visual acuity between medical antimicrobial treatments alone versus antimicrobial treatment plus collagen cross-linking (CXL), as well as to further evaluate findings from subgroup analyses of SCUT. Patients presenting to the Aravind Eye Care System (India), Kaiser Permanente Northern California (USA), or the University of California, San Francisco (USA) with smear-positive and/or culture-positive typical (i.e. non-Nocardia or Mycobacteria) bacterial corneal ulcers and moderate to severe vision loss, defined as Snellen visual acuity of 20/40 or worse, will be eligible for inclusion. Those who agree to participate will be randomized to one of three treatment groups:
Group 1: Standard therapy, topical 0.5% moxifloxacin plus topical placebo plus sham CXL Group 2: Early steroids, topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus sham CXL Group 3: CXL plus early steroids, topical 0.5% moxifloxacin plus topical difluprednate 0.05% plus CXL

Start Date24 Sep 2020

Sponsor / Collaborator

Aravind Eye Hospital

[+3]

100 Clinical Results associated with Difluprednate

100 Translational Medicine associated with Difluprednate

100 Patents (Medical) associated with Difluprednate

150

Literatures (Medical) associated with Difluprednate

24 Jan 2024·Journal of the American Veterinary Medical Association

Xanthogranulomatous keratitis in a mixed-breed dog

Article

Author: Herrmann, James ; Reilly, Christopher M ; Bergen, Alexandra

Abstract:

OBJECTIVE:

To evaluate the clinical and histopathological features of a case of xanthogranulomatous keratitis in a mixed-breed dog.

ANIMAL:

Mixed-breed dog.

CLINICAL PRESENTATION, PROGRESSION, AND PROCEDURES:

An 11-year-old spayed female mixed-breed dog was presented for mild blepharospasm, corneal cloudiness, and increasing conjunctival hyperemia OD. Ophthalmic examination revealed multifocal pink and cream-colored consolidated corneal infiltrative lesions and generalized neovascularization with suspected diagnosis of stromal abscessation. There was no improvement after 1 month of medical management, so a keratectomy was performed, and corneal tissue was sent for histopathological evaluation.

TREATMENT AND OUTCOME:

The nonulcerative keratitis was refractive to medical management including topical and systemic antibiotics, topical antifungal, and systemic anti-inflammatory, so keratectomy was performed. Histopathologic diagnosis of xanthogranulomatous keratitis was made 1 week postoperatively. The patient was prescribed 0.05% difluprednate ophthalmic emulsion and 0.2% tacrolimus ophthalmic ointment (initially q 8 h, OD). The difluprednate was tapered and discontinued after 2 months, but the tacrolimus was continued (q 12 h, OD). No lesion recurrence had been documented 1 year postoperatively.

CLINICAL RELEVANCE:

There has been little published on canine xanthogranulomas, especially in veterinary ophthalmology. Ocular xanthogranulomas have been reportedly found intraocularly and at the ocular surface. Histologically, they are characterized by well-delineated nodules that contain histiocytes and abundant lipid-laden macrophages. The treatment in this clinical case was surgical excision followed with topical immunosuppression/anti-inflammatory therapy with no recurrence 1 year postoperatively. Xanthogranulomatous keratitis should be an added differential diagnosis when nonulcerative keratitis is found on examination, specifically with consolidated, corneal infiltrate and minimal pain.

17 Jan 2024·Journal of current glaucoma practice

Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction

Article

Author: Birnbaum, Faith ; Wakil, Susan ; ElMallah, Mohammed ; Vu, Daniel M ; Tseng, Henry ; McBurney-Lin, Shan

Aim:

To review the efficacy and safety of two common postoperative regimens following Kahook Dual Blade goniotomy with phacoemulsification cataract extraction (KDB-CE).

Materials and methods:

This is a retrospective review of eyes undergoing KDB-CE from May 2016 to 2018 by a single surgeon. Almost 12-month follow-up data were assessed for two common postop regimens-treatment with (1) topical prednisolone acetate 1% with pilocarpine 1% (pred-pilo) or (2) difluprednate 0.05% postoperatively. Postoperative results were compared to each respective baseline intraocular pressure (IOP) levels.

Results:

There were 53 eyes in the difluprednate group and 25 eyes in the pred-pilo group. In the difluprednate group, the IOP decreased at postoperative day 1 (POD1) [16 ± 5 baseline vs 15 ± 5 POD1, mean ± standard deviation (SD) in mm Hg, and p = 0.321], but increased at postoperative week 1 (POW1) due to a 15% rate of IOP-spikes (19 ± 9, p = 0.099). The number of IOP-lowering drops decreased from baseline (2 ± 1 drops) to 1 ± 1 drops at POD1 (p < 0.0001), and remained at 1 ± 1 drops through postoperative month 12 (POM12) (p < 0.0001). In the pred-pilo group, there was a statistically significant decrease in mean IOP at POW1 (16 ± 4 POW1 vs 18 ± 6 baseline, p = 0.044), which persisted through POM6. The number of IOP-lowering drops was not statistically significantly lower from baseline at POM3 (2 ± 1 at POM3, p = 0.188). Spikes in IOP, corneal edema, and hyphema were the most common complications.

Conclusion:

Both postoperative regimens were effective following KDB-CE at reducing IOP at 12 months. The difluprednate group was likely to experience an IOP-spike at POW1 but used fewer IOP-lowering drops 12 months after KDB goniotomy. In the pred-pilo group, the number of IOP-lowering drops was equivalent to baseline levels at POM3. Aside from IOP spikes, there were similar complication rates observed between the two postoperative regimens. Due to demographic differences, it was not possible to compare relative IOP-lowering efficacy between the two postoperative regimens.

Clinical significance:

It is efficacious and safe to use either postoperative regimen following KBD-CE. Postoperative trajectories may differ with respect to the postoperative regimen, but further randomized controlled trials are needed to compare various topical steroid medications for postoperative regimens following KDB-CE.

How to cite this article:

Birnbaum F, Wakil S, Vu DM, et al. Postoperative Management of Kahook Dual Blade Goniotomy with Phacoemulsification Cataract Extraction. J Curr Glaucoma Pract 2023;17(4):169-174.

01 Jan 2024·EClinicalMedicine

Safety and efficacy of ixoberogene soroparvovec in neovascular age-related macular degeneration in the United States (OPTIC): a prospective, two-year, multicentre phase 1 study

Article

Author: Wykoff, Charles C ; Kiss, Szilárd ; Danzig, Carl J ; Major, James C ; Joondeph, Brian C ; Turpcu, Adam ; Boyer, David S ; Regillo, Carl D ; Khanani, Arshad M ; Busbee, Brandon G ; Pieramici, Dante

Background:

Gene therapy, successfully used in rare, monogenetic disorders, may prove to be a durable management approach for common, polygenetic conditions, including neovascular age-related macular degeneration (nAMD). Repeated injections, oftentimes monthly, and possibly for decades, of vascular endothelial growth factor antagonists (anti-VEGF), is the standard for nAMD. We hypothesised that an in-office, intravitreal administration of ixoberogene soroparvovec (ixo-vec, formerly ADVM-022), a single-dose gene therapy encoding for the proven anti-VEGF protein, aflibercept, would transform retinal cells to continually produce aflibercept to minimise treatment burden in nAMD.

Methods:

In this two-year, open-label, prospective, multicentre phase 1 study, patients with nAMD responding to anti-VEGF were assigned to four cohorts differing by ixo-vec dose (2 × 10¹¹ vs 6 × 10¹¹ vector genomes (vg/eye)) and prophylactic steroids (oral prednisone vs topical difluprednate). The primary outcome was the type, severity, and incidence of ocular and systemic adverse events (AEs); secondary endpoints included vision, central subfield thickness (CST), and the number of supplemental injections. This study was registered with ClinicalTrials.gov, NCT03748784.

Findings:

Thirty patients with nAMD were enrolled between November 14, 2018 and June 30, 2020 at nine study sites in the United States. No systemic ixo-vec related AEs were noted. Across both dose groups the most common adverse event was anterior chamber cell, which was reported in 11 participants in the 6 × 10¹¹ dose group and in 7 participants in the 2 × 10¹¹ dose group; intraocular inflammation was responsive to topical corticosteroids, with no anterior chamber cells or vitreous cells observed in 2 × 10¹¹ vg/eye patients at the end of the study. Vision and CST remained stable throughout two years with annualised anti-VEGF injections reduced by 80% (10.0 mean annualised anti-VEGF injections to 1.9) in 2 × 10¹¹ vg/eye and 98% (9.8 mean annualised anti-VEGF injections to 0.2) in 6 × 10¹¹ vg/eye cohorts.

Interpretation:

Ixo-vec was generally well-tolerated, maintained vision, and improved anatomical outcomes in nAMD, with a substantial reduction in anti-VEGF injections. A single administration of an in-office gene therapy, with vectorised protein with an already established clinical benefit, has the potential to revolutionise the management of common ocular disorders requiring ongoing, frequent therapeutic interventions.

Funding:

Adverum Biotechnologies.

News (Medical) associated with Difluprednate

08 Feb 2024

·www.fiercebiotech.com

UPDATE: Adverum's gene therapy reduces treatment burden in wet AMD, but questions remain

"On first blush," Mizuho analysts have dubbed Adverum Biotechnologies’ new data positive. Adverum Biotechnologies' gene therapy for wet age-related macular degeneration (AMD) reduced treatment burden and maintained visual acuity in a phase 2 study, though a full picture can't be formed yet from the slice of early data. The company's stock has fallen 18% to $2.28 compared to yesterday's market close price of $2.80 as of 10:45 a.m. ET today. The data center around ixo-vec, an AAV-based gene therapy formerly known as ADVM-022 but renamed in 2022. Adverum had previously assessed the intravitreal injection in diabetic macular edema, an effort that was eventually discontinued after a patient went blind in the treated eye. Now, interim ixo-vec data come from a phase 2 wet AMD study dubbed LUNA, with Adverum claiming the preliminary results demonstrate "potential best-in-class clinical activity in hard-to-treat patients including treatment burden reduction and maintenance of both visual acuity and anatomic endpoints." The phase 2, double-masked trial is designed to evaluate the safety and efficacy of a single IVT injection of ADVM-022 at one of two doses, a high dose (2E11 vg/eye) and low dose (6E10 vg/eye), accompanied by one of four prophylactic corticosteroid treatment regimens designed to reduce anticipated inflammation that is associated with AAV-based gene therapy. Among the 60 patients in the trial, no serious adverse events tied to the gene therapy were reported, according to Adverum. The biotech said ixo-vec was generally well tolerated, though specific safety data were not shared. According to Adverum, the best performing prophylactic regimen appears to be a combination of Ozurdex and Durezol eye drops, with "the vast majority of patients" receiving the combo having no inflammation and over 90% of patients having minimal inflammation. On the efficacy side, the biotech reported maintenance of both visual acuity and anatomic endpoints that measures central subfield thickness (CST). In a sub-group analysis of patients with higher baseline CST, a greater CST reduction was seen, according to Adverum. When looking at treatment burden reduction at 26 weeks, ixo-vec demonstrated annualized reduction in anti-vascular endothelial growth factor (anti-VEGF) injection rates of 90% among the 19 patients in the 6E10 cohort and 94% of the 20 patients in the 2E11 arm. At 26 weeks, ixo-vec demonstrated injection free rates of 68% for the 6E10 group and 85% of the patients in the 2E11 cohort. "Our goal with Ixo-vec is to provide patients virtually injection-free management of their wet AMD lasting years and potentially for life," Adverum CEO Laurent Fischer, M.D., said in a Feb. 8 release, dubbing ixo-vec a "one-and-done" gene therapy on a call with Fierce Biotech. Mizuho analysts' "initial reaction" to the data was positive: "On first blush, we saw no serious adverse events, and with respect to efficacy, the data appear to be better than that recently reported from two wAMD gene therapy competitors over the past week." The analyst firm is referring to data from competitor 4D Molecular Therapies and Regenxbio, both of which recently dropped respective phase 2 data in the indication. 4DMT reported an 89% and 85% reduction in annualized anti-VEGF injection rates in its high (3E10 vg/eye) and low (1E10 vg/eye) dose arms for 4D-150, rates slightly lower than those seen for Adverum. Regenxbio’s AbbVie-partnered ABBV-RGX-314 demonstrated the highest reduction in treatment burden in more than 50 patients receiving the third dose level, with an 80% reduction in annualized injection rate. Mizuho wasn’t quick to form a hard opinion, though, noting that “it may take time to fully digest the totality of this data set and others before we understand fully the efficacy and safety profile of ixo-vec and how it may stack up against its competitors.” Adverum is expected to share a 26-week interim analysis from LUNA in mid-2024. The biotech anticipates engaging in official discussions with the FDA about phase 3 trial design after those results are shared, Fischer told Fierce, with a potential phase 3 launch slated for the first half of 2025. Editor's note: This story was updated at 12:35 p.m. ET on Feb. 8 to include commentary from Adverum CEO Laurent Fischer.

Phase 2Phase 3Clinical ResultGene Therapy

08 Feb 2024

·www.biospace.com

Adverum Biotechnologies Announces Positive Preliminary Efficacy and Safety Data from LUNA Phase 2 Trial of Ixo-vec in Patients with Wet AMD

– Both dose levels (2E11 & 6E10) demonstrate potential best-in-class clinical activity in hard-to-treat patients including treatment burden reduction and maintenance of both visual acuity and anatomic endpoints – – Preliminary safety data support a favorable benefit-risk pro both dose levels – – Ozurdex + difluprednate identified as potential “go-forward” prophylaxis – – The vast majority of patients on the “go-forward” regimen had no inflammation and >90% of patients have no or minimal inflammation (0 or 0.5+ AC cells) – – Preliminary efficacy and safety data trending similar to or better than the OPTIC study, in which patients continue to see on-going clinical benefit through at least 3 years – – Webcast to be held today Thursday, February 8 at 8:00 a.m. EST – REDWOOD CITY, Calif., Feb. 08, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy as a new standard of care for highly prevalent ocular diseases, today announced preliminary safety and efficacy data from the ongoing LUNA Phase 2 trial in patients with wet age-related macular degeneration (AMD). These data are being presented by Dr. Arshad Khanani today at the 47th Annual Meeting of the Macula Society. The presentation titled “Ixoberogene soroparvovec (Ixo-vec) Intravitreal Gene Therapy for Neovascular Age-Related Macular Degeneration: Preliminary Results from the LUNA Phase 2 Study" is scheduled for 10:56am ET. “Wet AMD is a leading cause of blindness in people over the age of 65, requiring life-long anti-VEGF injections. Our goal with Ixo-vec is to provide patients virtually injection-free management of their wet AMD lasting years and potentially for life,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “We are pleased with the emerging treatment pro Ixo-vec, showing potential for best-in-class efficacy and over 90% of subjects having no or minimal inflammation with our go-forward local prophylactic regimen. Underscoring the potential best-in-class pro Ixo-vec, these early activity results were seen in hard-to-treat patients, who received over 9 annualized injections in the year prior to receiving Ixo-vec. Going into LUNA, we looked to replicate the robust clinical activity seen in OPTIC, in which patients continued to see clinical benefit through 3 years, with measured stable aflibercept through 4.5 years. We are proud to build upon our pioneering efforts with the most mature dataset and longest follow-up of all wet AMD intravitreal gene therapies currently in development.” Dr. Fischer continued, “Going into LUNA, we also looked to establish that an enhanced prophylactic regimen combined with highly active doses of Ixo-vec would further enhance its long-term benefit-risk profile. With these early data, we are pleased with the promising pro Ozurdex plus difluprednate which we expect to be our go-forward regimen. We look forward to sharing the maturing LUNA dataset with the goal of confirming the optimal dose(s) and prophylactic regimen for pivotal studies and with the plan to present our 26-week interim analysis in the middle of 2024.” “Based on my experience as an investigator for over five years across multiple clinical trials with Ixo-vec for wet AMD, it’s promising to see the sustained disease control and a significant treatment burden reduction after a single intravitreal injection of Ixo-vec in previously treated patients with wet AMD,” said Arshad M Khanani, M.D., M.A., FASRS, Managing Partner and Director of Clinical Research at Sierra Eye Associates, Clinical Associate Professor at University of Nevada, Reno and Principal Investigator in LUNA trial. “Ixo-vec has the potential to shift the treatment paradigm for patients with wet AMD and I look forward to working with the Adverum team to advance Ixo-vec into pivotal studies.” LUNA Trial Background and Baseline Demographics The LUNA trial is an ongoing double-masked, randomized, Phase 2 trial. 60 patients with wet AMD were enrolled equally across two dose cohorts, 2E11 and 6E10 vg/eye. The study is designed to assess optimized prophylactic regimens, with patients receiving one and/or two locally administered corticosteroid regimens, with or without oral prednisone. The LUNA trial builds on our experience with the OPTIC study, where landmark 2-year data was recently published in The Lancet’s eclinicalmedicine. The data cut-off for these data is November 15, 2023, except for treatment burden reduction, which is of January 2, 2024. LUNA Preliminary Efficacy and Safety Data Summary Both the 2E11 and 6E10 doses demonstrated maintenance of visual and anatomic outcomes. Notably, both doses resulted in a potentially best-in-class reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients remaining free of annualized injections, with data trending similar to or better than the OPTIC study. Treatment Burden Reduction At 26 weeks, Ixo-vec demonstrated annualized reduction in anti-VEGF injection rates of 90% (n=19) at 6E10 and 94% (n=20) at 2E11. At 26 weeks, Ixo-vec demonstrated injection free rates of 68% (n=19) at 6E10 and 85% (n=20) at 2E11. Visual (BCVA) and Anatomic (CST) Outcomes: Visual acuity was maintained at both dose levels - mean BCVA change from baseline to last visit (95% CI): 2E11: -1.7 (-4.5, 1.2) 6E10: +0.5 (-2.2, 3.3) Anatomic endpoints were maintained at both dose levels - mean CST (μm) change from baseline to last visit (95% CI): 2E11: -16.4 (-31.5, -1.3) 6E10: -7.9 (-30.9, 15.0) In a sub-group analysis of patients with higher baseline CST, a greater reduction in CST was demonstrated, indicating the robust efficacy potential of Ixo-vec gene therapy. Safety Preliminary data suggest corticosteroid prophylaxis optimization at both the 2E11 and 6E10 doses appears to result in improved inflammatory profiles in LUNA as compared to OPTIC study results. Ixo-vec was generally well-tolerated, and when present intraocular inflammation was responsive to local corticosteroids. No Ixo-vec related serious adverse events were reported. No episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported. Preliminary data indicate that select prophylactic regimens are outperforming others that do not provide sustained prophylaxis. Early on in the study, the company implemented a protocol amendment to augment the Ozurdex containing regimens with a course of Durezol eye drops. Preliminary data indicate that the amended Ozurdex + Durezol regimen may be the favorable prophylactic regimen for future pivotal studies. In this potential “go-forward” regimen, the vast majority of patients had no inflammation, with over 90% of these patients having no or minimal inflammation. Oral corticosteroids showed no incremental benefit. Upcoming Ixo-vec Milestones LUNA 26-week interim analysis expected mid-2024 Continued FDA and EMA formal and informal regulatory interactions Initiation of Phase 3 trial expected H1’25 Webcast Details The live webcast will be accessible under Events and Presentations in the Investors section of the company's website. Listeners can register for the webcast via this webcast link. Analysts wishing to participate in the question and answer session should use this dial-in link. A replay of the webcast will be available on the company’s website shortly after the conclusion of the webcast. About Wet Age-Related Macular Degeneration Wet AMD, also known as neovascular AMD or nAMD, is a VEGF driven advanced form of AMD affecting approximately 10% of patients living with AMD associated with the build-up of fluid in the macula and the retina. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases. Additionally, wet AMD is a bilateral disease, and incidence of nAMD in the second eye is up to 42% in the first two to three years. The current standard of care requires frequent life-long repeated bolus injections of anti-VEGF in the eye. IVT gene therapy has the promise to preserve vision and reduce most or all injections for the life of the patient by delivering stable therapeutic levels of anti-VEGF to control macular fluid. About Ixo-vec in Wet AMD Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-VEGF, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, FDA granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec has also received PRIME designation from the EMA and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD. About Adverum Biotechnologies Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. Additionally, by overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit Forward-looking Statements Statements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding the potential benefits of Ixo-vec as a one-time IVT injection for the treatment of wet AMD, including its potential to improve vision outcomes, the potential best-in-class efficacy of Ixo-vec, and anticipated timing of preliminary and interim data from the Phase 2 LUNA trial and initiation of a Phase 3 trial. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 9, 2023. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Inquiries: Adverum Investor Relations Email: ir@adverum.com

Clinical ResultPhase 2Gene TherapyFast TrackPhase 3

25 May 2023

·www.biospace.com

Adverum Biotechnologies Announces New Executive Leadership Roles

Richard Beckman, M.D., chief medical officer, transitions to senior medical advisor - Star Seyedkazemi, Pharm.D., chief development officer, expands her responsibilities to lead Adverum’s clinical development, medical affairs and pharmacovigilance teams - REDWOOD CITY, Calif., May 25, 2023 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced new executive leadership roles that support the ongoing development of the investigational gene therapy ixoberogene soroparvovec (Ixo-vec). Ixo-vec is currently being evaluated in the Phase 2 LUNA trial as a one-time intravitreal (IVT) injection for patients in the treatment of neovascular or wet age-related macular degeneration (wet AMD). On June 1, 2023, Richard Beckman, M.D., will transition to the new role of senior medical advisor. Dr. Beckman will continue to advise on Adverum’s pipeline, including Ixo-vec, and support our external engagement with key stakeholders. Star Seyedkazemi, Pharm.D., chief development officer, is expanding her responsibilities to lead Adverum’s clinical development, medical affairs and pharmacovigilance teams. Dr. Seyedkazemi brings extensive experience in clinical development and medical affairs from Tobira, Allergan, Gilead Sciences and Johnson & Johnson. Dr. Seyedkazemi will be supported by Kali Stasi, M.D., Ph.D., senior vice president of clinical development. Dr. Stasi brings over 20 years of experience in both ophthalmology and drug development, specializing in retinal gene and cell therapies. She was previously at Novartis Institute for Biomedical Research and Tenpoint Therapeutics. Dr. Beckman and Dr. Seyedkazemi will continue to report to Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “On behalf of Adverum and our Board of Directors, I’d like to thank Rick for his important contributions to Adverum in advancing Ixo-vec in the clinic and building out the clinical development and pharmacovigilance teams,” commented Dr. Fischer. “I am pleased that he will continue to work with Adverum in his role as senior medical advisor. Over the last year, Adverum has made tremendous progress, including the successful launch of our LUNA trial and outstanding progress in the global development strategy for Ixo-vec, including attaining of PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency.” “Throughout my career, I have wanted to advance transformational medicines with the potential to improve the practice of ophthalmology and bring tangible benefits to patients,” stated Richard Beckman, M.D., chief medical officer of Adverum Biotechnologies. “The Phase 2 LUNA trial brings us a step closer to our mission of establishing gene therapy as a new standard of care for wet AMD. I look forward to my continued work with Laurent, Star and the team.” Anticipated LUNA 2023 Milestones 2H 2023 – Anticipate full enrollment of the Phase 2 LUNA trial Q3 2023 – Anticipate LUNA 14-week data, including aflibercept protein levels for a percentage of the cohort Q4 2023 – Anticipate LUNA preliminary efficacy and safety data About Wet Age-Related Macular Degeneration Wet AMD, also known as neovascular AMD or nAMD, is an advanced form of AMD affecting approximately 10% of patients living with AMD. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases. Additionally, wet AMD is a bilateral disease and incidence of nAMD in the second eye is up to 42% in the first two to three years. About Ixo-vec in Wet AMD Adverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD. About LUNA Trial of Ixo-vec in Wet AMD The LUNA trial is a double-masked, randomized, Phase 2 trial being conducted at approximately 40 sites in the U.S. and Europe. LUNA will evaluate Ixo-vec in subjects with wet AMD who are 50 years or older and have demonstrated a response to anti-VEGF treatment. Up to 72 subjects will be randomized equally between the previously evaluated 2E11 vg/eye dose and a new, lower 6E10 vg/eye dose. Four prophylactic corticosteroid regimens will be studied with the aim of establishing a prophylactic corticosteroid regimen with minimal need for inflammation management post prophylaxis. Prophylactic regimens being evaluated include 22 weeks of a tapered regimen of topical difluprednate (Durezol®), a single administration of IVT dexamethasone (Ozurdex®), and a combination of either topical Durezol® or IVT Ozurdex® with up to 10 weeks of a tapered regimen of oral prednisone. All four prophylactic corticosteroid regimens in LUNA cover the period of peak immunogenicity observed in non-clinical studies and in the Phase 1 OPTIC study. The LUNA trial primary endpoints are mean change in best corrected visual acuity (BCVA) from baseline to one year, as well as the incidence and severity of adverse events. Important secondary endpoints in LUNA include the mean change in central subfield thickness (CST) from baseline to one year and assessing the effectiveness of prophylactic corticosteroid regimens on minimizing inflammation. Additionally, LUNA will assess aflibercept protein levels starting at Week 14 and include an interim analysis at Week 26. Study participants will have the option to enroll in a long-term extension study. About Adverum Biotechnologies Adverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit Forward-looking Statements Statements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding the potential benefits of Ixo-vec in the treatment of wet AMD, the design of and enrollment in the LUNA trial, including the prophylactic corticosteroid regimens, and anticipated interim data from the LUNA trial. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 filed with the SEC on May 11, 2023. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Corporate, Investor and Media Inquiries Anand Reddi Vice President, Head of Corporate Strategy, External Affairs and Engagement Adverum Biotechnologies, Inc. T: 650-649-1358 E: areddi@adverum.com

Phase 2Gene TherapyFast TrackPhase 1Executive Change

100 Deals associated with Difluprednate

External Link

KEGG	Wiki	ATC	Drug Bank
D01266	Difluprednate	D07AC19	DB06781

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Uveitis, Anterior	US	Sandoz, Inc.	13 Jun 2012
Inflammation	US	Sandoz, Inc.	23 Jun 2008
Pain	US	Sandoz, Inc.	23 Jun 2008
Alopecia Areata	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Eczema	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Erythrodermic psoriasis	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Granuloma	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Insect Bites and Stings	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Keloid	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Lupus Erythematosus, Discoid	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986
Prurigo	JP	Mitsubishi Tanabe Pharma Corp.	30 Jun 1986

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Eye Pain	Phase 3	IN	Sun Pharma Advanced Research Co. Ltd.	30 Jan 2022
Ocular inflammation	Phase 3	IN	Sun Pharma Advanced Research Co. Ltd.	30 Jan 2022
Cataract	Phase 3	US	Alcon Research Ltd.	01 Aug 2010
Uveitis	Phase 3	US	Sirion Therapeutics, Inc.	16 Jul 2007
Post procedural inflammation	Phase 3	-	Sirion Therapeutics, Inc.	01 Apr 2004
Cyclitis	Phase 2	-	Sirion Therapeutics, Inc.	01 Mar 2000
Iridocyclitis	Phase 2	-	Sirion Therapeutics, Inc.	01 Mar 2000
Iritis	Phase 2	-	Sirion Therapeutics, Inc.	01 Mar 2000
Diabetic macular oedema	Phase 2	JP	Senju Pharmaceutical Co., Ltd.	-
Dry Eye Syndromes	Phase 2	US	Alcon AG	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2023	Not Applicable	Non-infectious posterior uveitis	22	difluprednate	txugrymdmn(wgxbftwtse) = mkdioyxssk qsnksudwsm (oqzmuikbbo, 32(27 - 36))	-	01 Jun 2023
ARVO2023	Not Applicable	Non-infectious posterior uveitis	22	difluprednate	txugrymdmn(wgxbftwtse) = uqdngtixoh qsnksudwsm (oqzmuikbbo, 32(27 - 36))	-	01 Jun 2023
PO440 (AAO2022)	Not Applicable	Scleritis	31	Difluprednate and systemic therapy	imvusawwyu(cadjosroqi) = kvezgfbodt wzcvxburty (ufkvjrwpjo )	Positive	29 Sep 2022
ARVO2022	Not Applicable	-	39	Topical difluprednate	nnmpusvkmz(gfdegfcthk) = oyztowjjto eeelbwztsf (oeiuvznkci )	-	01 May 2022
ARVO2021	Not Applicable	Scleritis	-	Difluprednate	aorxlywfho(rughvkmlnu) = mqyvbhpvjj hbfkhrmjnz (naaaxkzxls ) View more	-	01 Jun 2021
ARVO2021	Not Applicable	Uveitis	30	Patients treated with topical difluprednate	qwmhqjwytk(hygbnuivds) = wbdpmnaizz edmjtakjpf (enpmiqtndc ) View more	-	01 Jun 2021
NCT03426267 (CTgov)	Phase 3	Pain \| Inflammation	325	SDN-037 (SDN-037)	qhkwwuftjw(bwidionzyc) = spvnykgekx xosjkmkgzm (rlcuajsmvf, pryovrvpbq - qkplvtzzpm) View more	-	17 May 2021
NCT03426267 (CTgov)	Phase 3	Pain \| Inflammation	325	Placebo (Vehicle)	qhkwwuftjw(bwidionzyc) = jecenvrdmq xosjkmkgzm (rlcuajsmvf, qgphwgtejn - gchyitbxaz) View more	-	17 May 2021
NCT03693989 (phase III, ARVO2020)	Phase 3	Post procedural inflammation	171	Difluprednate 0.05%	nnwsztgtdo(lgydosseep) = tftmpxvwqm ukwsohwxkk (srjhuyyymh ) View more	Positive	01 Jun 2020
NCT03693989 (phase III, ARVO2020)	Phase 3	Post procedural inflammation	171	Prednisolone acetate 1%	nnwsztgtdo(lgydosseep) = ardqmxkkve ukwsohwxkk (srjhuyyymh ) View more	Positive	01 Jun 2020
NCT03693989 (phase III, CTgov)	Phase 3	Cataract \| Pain \| Inflammation	178	Difluprednate 0.05% (PRO-145.)	symmbvbdho(yrqjlkvxkn) = bixckxuvaa cpajstdptz (asdydvwrjo, bwyxqbfkiv - pmknubsdob) View more	-	02 Dec 2019
NCT03693989 (phase III, CTgov)	Phase 3	Cataract \| Pain \| Inflammation	178	Prednefrin (Prednefrin)	symmbvbdho(yrqjlkvxkn) = eieeydpuwc cpajstdptz (asdydvwrjo, hcswdeijtw - uwxavsyizc) View more	-	02 Dec 2019
PO131 (AAO2016)	Not Applicable	Non-infectious posterior uveitis	-	Topical Difluprednate 0.05%	gsmajxmcxc(djxapkgidz) = xwtcnlhasx xlhxphaskj (kyhrrwoeew ) View more	Positive	16 Oct 2016
ARVO2016	Not Applicable	Non-infectious posterior uveitis	6	Topical difluprednate	rdnfbjdgle(rsqerfefwp) = ghweatvchh watlskxxpe (tspbkmxkof, 0.6)	-	01 Sep 2016

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Leverages most recent intelligence information, enabling fullest potential.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis