Difluprednate

New Delhi: Caplin Point Laboratories Ltd on Monday said its arm Caplin Steriles Ltd has received approval from the US health regulator for its generic version of Difluprednate eye drop indicated in the treatment of inflammation and pain associated with ocular surgery. The approval granted by the US Food and Drug Administration (USFDA) is for the abbreviated new drug application (ANDA) of Difluprednate Ophthalmic emulsion, 0.05 per cent, Caplin Point Laboratories said in a regulatory filing. It is a generic therapeutic equivalent version of the Reference Listed Drug (RLD) DUREZOL, from Sandoz Inc, the company said. "We're pleased to receive a first cycle approval for this complex emulsion product. Few more emulsion and suspension products have been filed or in the pipeline, which should augment Caplin Steriles' portfolio in the US and emerging markets," Caplin Chairman CC Paarthipan said. Difluprednate ophthalmic emulsion, 0.05 per cent (eye drops) is a topical corticosteroid that is indicated in the treatment of inflammation and pain associated with ocular surgery, and in the treatment of inflammation inside the eyes. Citing IQVIA data, the company said Difluprednate ophthalmic emulsion, 0.5 per cent, had US sales of approximately USD 21 million for the 12-month period ending October 2024.

- 52-week LUNA data combined with follow-up from OPTIC at 4 years continue to support long-term potential best-in-class product profile of Ixo-vec - 6E10 dose in LUNA maintains visual and anatomic endpoints and demonstrates potential best-in-class injection-free rates and reduction in injection burden - No LUNA patients who received local steroid prophylaxis had inflammation at week 52 or at any subsequent visit, and 100% of OPTIC 2E11 patients were free of inflammation at year 1 and through year 4 - 6E10 with steroid eye drops or topical steroids to progress into two registrational studies; initial ARTEMIS Phase 3 non-inferiority study will evaluate a broad patient population; on track and expected to initiate in 1H 2025 - Investor & analyst webcast, including a key opinion leader panel, to be held Monday, November 18th at 7:30 a.m. EST REDWOOD CITY, Calif., Nov. 18, 2024 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company pioneering the use of gene therapy to preserve sight for life in highly prevalent ocular diseases, today announced topline 52-week results from the LUNA Phase 2 trial, new 4-year OPTIC long-term follow-up data and key pivotal program design elements. “We are thrilled to report 52-week LUNA data and 4-year OPTIC data that continue to support Ixo-vec as a transformative and potential best-in-class therapy, which may provide patients who have wet AMD with potentially life-long benefit and a predictable safety profile. Both OPTIC 2E11 results and LUNA efficacy data at 52 weeks show maintenance of visual and anatomic endpoints with over 80% reduction in injection burden and greater than 50% injection freedom. These consistent results are bolstered by our OPTIC long-term data where we have demonstrated stable therapeutic aflibercept levels through 5 years. The data across both studies support a reliable long-term benefit and a predictable safety profile,” stated Laurent Fischer, M.D., president and chief executive officer of Adverum Biotechnologies. “Ultimately, Ixo-vec is a potential paradigm-shifting solution for patients with wet AMD, where real-world evidence suggests that up to 57% of patients stop anti-VEGF treatment within 5 years, and the vast majority of patients end up losing vision. Designed as a single, one-time intravitreal injection, Ixo-vec has the potential to extend therapeutic benefit from weeks to years. Today’s 4-year OPTIC data suggest that Ixo-vec may preserve vision for the life of wet AMD patients.” “We have designed our Ixo-vec Phase 3 pivotal program to establish gene therapy as a standard of care for all wet AMD patients. Our ARTEMIS trial design considers feedback from key stakeholders, including global regulatory authorities, key opinion leaders, and patients, thereby optimizing for Ixo-vec’s potential clinical, regulatory and commercial success,” stated Rabia Gurses Ozden, MD, Chief Medical Officer at Adverum. “Today’s LUNA 52-week data support our decision to advance the 6E10 dose and topical-eyedrops-only prophylaxis into Phase 3. One of the unique, and in my view, profound aspects of this LUNA update was the near unanimous patient preference for Ixo-vec, as assessed via a pre-specified patient survey. The vast majority preferred Ixo-vec over their prior intravitreal injections. No patients on topical eyedrops alone stated that the steroid eyedrops were difficult to manage. And 100% of patients who received Ixo-vec 6E10 and eyedrops alone preferred Ixo-vec over prior anti-VEGF treatments.” “The LUNA 52-week clinical data further establish that the 6E10 dose of Ixo-vec has the potential to meaningfully reduce treatment burden for patients with wet AMD, even among patients with highly active disease who are receiving frequent dosing,” said Charles Wykoff, MD, PhD, Director of Research, Retina Consultants of Texas, Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital and a principal investigator for LUNA. “Encouragingly, the 6E10 dose with extended prophylaxis also resulted in less inflammation. Taking these LUNA results together with 4-year data from the 2E11 dose in OPTIC, the totality of data indicates a predictable immune response with inflammation that, if it occurs, is manageable with local steroids, doesn’t impact vision, and ultimately resolves. These data from LUNA and OPTIC studies suggest a favorable benefit-risk profile for patients, which I believe many patients would consider if Ixo-vec were available in routine clinical practice. I look forward to working with the Adverum team as Ixo-vec advances toward pivotal studies next year.” LUNA Phase 2 Trial and OPTIC First-in-Human Trial - Background and Baseline Prior Anti-VEGF Injections LUNA is an ongoing double-masked, randomized Phase 2 trial. 60 patients with wet AMD were randomized equally across two dose cohorts, 6E10 or 2E11 vg/eye. The trial is evaluating multiple prophylactic regimens, including topical steroid eyedrops (difluprednate) with or without Ozurdex® and with or without oral steroids. LUNA is designed to inform the selection of both the Ixo-vec dose and prophylactic regimen for Phase 3 registrational trials. OPTIC is an ongoing, open-label, dose-ranging first-in-human trial. 30 patients with wet AMD requiring frequent IVT injections were enrolled equally across two doses, 2E11 or 6E11. Patients received either six weeks of prophylactic topical steroid eye drops or 13 days of prophylactic oral steroids. The OPTIC trial was a two-year study, with an optional 3-year extension. The LUNA and OPTIC data cutoff dates were August 29, 2024, and August 21, 2024, respectively. At the data cutoff date for LUNA, 57 patients had completed the 52-week study visit, with 3 discontinuations due to adverse events unrelated to study drug. 23 OPTIC patients elected to participate in the OPTIC extension. At the data cutoff date for OPTIC, 21 patients had completed the 4-year study visit, with 2 discontinuations unrelated to study drug. Both LUNA and OPTIC were designed to assess a broad wet AMD population, including hard-to-treat patients with severe disease who required frequent anti-VEGF injections before enrolling in the trial. At baseline, mean annualized prior anti-VEGF injections in the year prior to enrolling in LUNA and OPTIC were 10.1 (2.6 SD) and 9.9 (1.9 SD), respectively. LUNA 52-week Analysis Topline Data Summary Both doses of Ixo-vec maintained visual and anatomic endpoints through 52 weeks. Best Corrected Visual Acuity (BCVA) - least squares mean BCVA change from baseline at week 52 (95% CI)1: 6E10: -2.1 (-4.8, 0.7)2E11: -1.8 (-4.6, 0.9) 1. Excludes 1 participant at each dose with letter loss due to cataract Central Subfield Thickness (CST) - least squares mean CST (μm) change from baseline at week 52 (95% CI): 6E10: -10.2 (-29.0, 8.5)2E11: -21.9 (-40.4, -3.3) Both doses of Ixo-vec achieved an industry leading treatment burden reduction and proportion patients who were injection free through 52 weeks. Treatment Burden Reduction - % reduction in mean annualized anti-VEGF injections: 6E10: 88% treatment burden reduction2E11: 92% treatment burden reduction Proportion of Patients Injection Free: 6E10: 54% injection free, with 75% of patients with ≤1 injection2E11: 69% injection free, with 79% of patients with ≤1 injection Both doses of Ixo-vec were well tolerated, with local steroids effectively managing inflammation when present. No 6E10 patients had inflammation at week 52 or at any subsequent visit2.No Ixo-vec-related serious adverse events. All Ixo-vec-related AEs were either mild or moderate: no episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony.The most common Ixo-vec-related AEs were dose-dependent anterior inflammation responsive to local corticosteroids and anterior pigmentary changes with no impact on vision.No new onset inflammation after week 30. 2. Inflammation defined as grade ≥ 1 AC/VC cells 6E10 dose with topical eyedrops as prophylactic regimen selected for pivotal program, providing a predictable long-term favorable safety profile. No patients at 6E10 with topical eyedrops had inflammation at week 52 or at any subsequent visit.Only one subject had inflammation, which resolved by year 1. LUNA results underscored by sub-group analyses that support potential best-in-class product profile and position Ixo-vec for potential clinical, regulatory and commercial success. Demonstrated consistent benefit in both patients with ≤300 μm baseline CST (“dry”) and patients with > 300 μm baseline CST (“wet”).Demonstrated maintenance of visual and anatomic outcomes in injection-free patients.Demonstrated even more robust clinical activity in patients with less treatment burden (experienced patients with <6 injections in year prior to LUNA). Results from our LUNA patient preference survey demonstrate strong preference for Ixo-vec over prior anti-VEGF therapies and acceptability of steroid regimen. 93% (n=56) of LUNA patients at 52 weeks prefer Ixo-vec, including accompanying steroid regimen, over prior treatments. Patient preference for Ixo-vec over prior treatments increased over time, from 88% (n=57) at 26 weeks.95% (n=56) of LUNA patients would elect to receive Ixo-vec in the other eye if both eyes had wet AMD.96% (n=56) of LUNA patients would recommend Ixo-vec to their family or friends with wet AMD.100% (n=10) of patients on the 6E10 pivotal dose and topical eyedrop steroid regimen prefer Ixo-vec over prior treatments for wet AMD.100% (n=10) of patients on the 6E10 pivotal dose and topical eyedrop steroid regimen would elect to receive Ixo-vec in other eye if both eyes had wet AMD.100% (n=10) of patients on the 6E10 pivotal dose and topical eyedrop steroid regimen would recommend Ixo-vec to their family or friends with wet AMD.No patients receiving topical eyedrop alone prophylaxis (n=20) stated it was difficult to manage. OPTIC (2E11) 4-year Analysis Topline Data Summary Patients in OPTIC received 9.9 mean annualized injections prior to receiving Ixo-vec. Despite significant treatment need at baseline, these patients continue to experience long-term benefit from Ixo-vec through at least 4 years of follow up, including maintenance of vision, durability of anatomical improvements and sustained reduction in anti-VEGF treatment burden. Aflibercept levels have been demonstrated up to 5-years post-treatment. Patients had an 86% reduction in annualized anti-VEGF injections through year 4, with a robust reduction in treatment burden demonstrated in each year following Ixo-vec administration. Through Year 1: 84% reduction in anti-VEGF injectionsThrough Year 2: 81% reduction in anti-VEGF injectionsThrough Year 3: 84% reduction in anti-VEGF injectionsThrough Year 4: 86% reduction in anti-VEGF injections 4-year OPTIC data underscore Ixo-vec’s reliable long-term benefit. Nearly 50% of patients were injection free through 4 years following Ixo-vec treatment.78% of OPTIC participants who were injection free through year 1 remained injection free through year 4.88% of OPTIC participants who were injection free through year 2 remained injection free through year 4.Durable aqueous aflibercept protein levels up to 5 years after a single Ixo-vec IVT injection. Ixo-vec at 2E11 was generally well tolerated and demonstrated a favorable safety profile. Inflammation was dose dependent, did not impact vision and, when present, was responsive to local corticosteroids.Long-term data establish a 10-fold safety margin from highest dose tested in nAMD. Key Design Elements of the Ixo-vec Phase 3 Pivotal Program The company plans to conduct two, double-masked, randomized Phase 3 clinical trials.The initial 284-patient, US-based ARTEMIS Phase 3 study is expected to enroll a broad patient population, including both treatment-naïve and treatment-experienced wet AMD patients.The primary endpoint, measured at an average of weeks 52 and 56, is non-inferiority (NI) in mean BCVA change from baseline between Ixo-vec (6E10 vg/eye) and aflibercept (2mg Q8W). The non-inferiority margin for this study is -4.5 letters.All patients will receive three monthly loading doses of aflibercept prior to Ixo-vec.The study will utilize a sham in the control arm to support masking. Patients in both arms will be eligible for supplemental injections of aflibercept and will receive topical steroid eye drops.This trial design is based on our end-of-Phase 2 feedback from the U.S. Food and Drug Administration (FDA).ARTEMIS remains on track and is expected to initiate in 1H 2025. Updated Cash Runway Guidance As of September 30, 2024, the company had $153.2 million in cash, cash equivalents and short-term investments. The company expects to be able to fund operations into the second half of 2025, which does not include completion of the ARTEMIS Phase 3 trial. Webcast Details The live webcast will be accessible under Events and Presentations in the Investors section of the company’s website. Listeners can access the webcast through this link: https://investors.adverum.com/events-and-presentations. A replay 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 www.adverum.com. 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 long-term potential best-in-class product profile of Ixo-vec; potential best-in-class injection-free rates and reduction in injection burden of Ixo-vec; the trial design of the Ixo-vec Phase 3 pivotal program and anticipated initiation timing; the potential of Ixo-vec to be transformative and a best-in-class therapy; the potential life-long therapeutic benefit and predictable safety profile of Ixo-vec; the potential of Ixo-vec to shift the treatment paradigm for patients with wet AMD; the ability to establish gene therapy as a standard of care for wet AMD patients; the likelihood of clinical, regulatory and commercial success of Ixo-vec; the Company’s cash sufficiency and runway; and other statements that are not historical fact. 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; the potential for future complications or side effects in connection with use of Ixo-vec; and risks associated with market condition. 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, 2024 filed with the SEC on November 4, 2024 and subsequent filings with the SEC. 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