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    2021 Research Update: Early-stage treatments

    Macular disease research in the early stages of development.

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    Treatments in early-stage development

    Many potential drugs enter early-stage development. Phase I tests safety in a small number of people. Phase II extends safety testing and seeks to show a proof of concept of efficacy. Only a few treatments will progress to late-stage development.

    MDFA’s entire 2021 Macular Disease Research Update – including treatments in more advanced stages of development – is also available on our website.

    Risuteganib (Luminate®) [Other]

    Risuteganib, developed by Allegro Ophthalmics, is a small, synthetic peptide that reduces inflammation and retinal degeneration. The drug is administered by eye injection.

    Results of a phase II clinical study in patients with intermediate AMD were published in 2021. Intravitreal risuteganib was administered on day zero and week 16. At 32 weeks the drug improved vision and had an acceptable safety profile.

    It is anticipated that a phase II/III will be initiated in the USA.

    AKST4290 [nAMD] [DMO]

    AKST4290, being developed by Alkahest, is an inhibitor of CCR3, a mediator of inflammation thought to be important in AMD. The drug is taken twice daily by mouth.

    A phase II clinical trial of 30 patients with nAMD showed that a six-week course of ALK4290 was well tolerated and increased visual acuity in most patients. A second trial of 26 patients with nAMD unresponsive to prior treatment showed modest improvements in vision.

    A third phase II study included 107 patients with nAMD treated over 36 weeks with aflibercept who additionally received one of two doses of AKST4290 or placebo. This study is complete and results are expected soon.

    A phase II study of AKST4290 in patients with diabetic macular oedema was started in September 2021 and is currently recruiting patients in the USA. Results are expected in late 2022.

    RBM-007 [nAMD]

    RBM-007, in development by RIBOMIC, inhibits fibroblast growth factor 2 and aims to reduce new blood vessel formation and scarring (fibrosis) in several diseases including nAMD.

    RBM-007 is administered as monthly eye injections. Initial results of the phase I/II SUSHI trial in nAMD were positive.

    The TOFU trial in nAMD compared four monthly RBM-007 injections alone or combined with every-other-month aflibercept versus aflibercept alone. Patients completing the TOFU study can enter the RAMEN study for an additional four monthly treatments of RBM-007. Both studies are ongoing and due to complete by the end of 2021.

    Triamcinolone acetonide (CLS-TA, Xipere®) [DMO]

    CLS-TA (Xipere®), developed by Clearside Biomedical, is a proprietary formulation of the steroid triamcinolone acetonide. The product features a novel micro-injector which uses a tiny needle to deliver drug between the retina and sclera (white) of the eye called the suprachoroidal space.

    The phase II TYBEE study in patients with DMO has been published. All patients received aflibercept monthly to week 12, then as needed. Patients who also received CLS-TA at baseline and week 12 required fewer aflibercept injections over 24 weeks.

    In October 2021, Xipere® was approved in the USA for the treatment of macular oedema associated with uveitis.

    In 2021, two phase III studies (TOPAZ, SAPPHIRE) in patients with RVO were terminated due to lack of additional benefit from CLS-TA injection.

    Axitinib (CLS-AX) [nAMD]

    CLS-AX, also developed by Clearside Biomedical, is a proprietary suspension of axitinib, an inhibitor of VEGF receptors. It is expected to offer ‘pan-VEGF’ inhibition in multiple macular diseases.

    This product features the same novel micro-injector for suprachoroidal injection.

    The phase II OASIS study in nAMD is currently under way and is expected to provide results in mid-2022.

    GT005 [GA]

    GT005, developed by Gyroscope Therapeutics, is a gene vector therapy to treat geographic atrophy (atrophic ‘dry’ AMD) administered by a one-time injection under the retina. It delivers the complement factor I gene into the retina where it will inhibit the complement system which has been implicated in GA.

    Three trials are recruiting patients with GA with a genetic deficiency in complement factor I.

    The phase I/II FOCUS is testing a range of doses and injection mechanisms. Interim results presented in September 2021 indicate the treatment is well tolerated and the gene is functional.

    The phase II HORIZON study will include 180 participants and will test two different doses of the vector versus sham. Data are expected in late 2022.

    Finally, the phase II EXPLORE trial will evaluate a lower dose of GT005 compared with a high dose and sham. Results are anticipated in 2023.

    Sunitinib maleate (GB-102) [nAMD] [DMO] [RVO]

    GB-102, developed by GrayBug Vision, is a proprietary suspension of sunitinib maleate, an inhibitor of VEGF receptors. It is expected to offer ‘pan-VEGF’ inhibition in multiple macular diseases.

    GB-102 is formulated as a slow-release treatment that only needs to be injected into the eye twice per year.

    The phase II ALTISSIMO study in nAMD showed GB-102 had a durable effect and was well tolerated. The study is ongoing.

    A second phase II study in patients with macular oedema due to diabetes or RVO showed GB-102 was well tolerated. Development continues.

    GEM-103 [nAMD] [GA]

    GEM103, being developed by Gemini Therapeutics, is a recombinant human complement factor H protein that aims to regulate the complement system, which has been implicated in the pathology of GA.

    GEM103 is being investigated in two phase II studies. The REGATTA study in patients with GA is investigating the safety of multiple eye injections of GEM103. Results are expected early 2022.

    The second study enrolled patients with nAMD and evaluates GEM103 as an add-on to aflibercept dosed according to label.

    CU03 [nAMD]

    CU03, developed by CURACLE, is an oral medication that aims to inhibit blood vessel leakage in various diseases including nAMD and DMO.

    A phase II study to evaluate safety, tolerability and efficacy recently completed patient observations and is expected to report in late 2021.

    CU06-RE [nAMD] [DMO]

    CU06-RE is another oral medication being developed by CURACLE that aims to inhibit blood vessel leakage in various diseases including nAMD and DMO.

    A phase I clinical trial in healthy volunteers is under way to determine an appropriate dose.

    In October 2021, CURACLE agreed to partner with Théa Open Innovation to develop the product.

    RPE Cell Transplant (OpRegen®) [GA]

    Retinal pigment epithelium (RPE) cells are lost in the course of geographic atrophy. OpRegen® is a single injection of human RPE cells derived from stem cells, being developed by Lineage Cell Therapeutics, that aims to replace lost cells.

    In September 2021, interim results were reported from a phase I/II clinical trial. With a minimum of nine months observation after treatment, most patients had better vision than at baseline. Overall, the intervention appears to be well tolerated.

    These findings are from a small group of patients and are preliminary. More complete results are expected in 2022, and the study is expected to conclude in 2024.

    PAN-90806 [nAMD]

    PAN-90806, in development by PanOptica, is a once-daily topical eye drop containing a suspension of a small molecule inhibitor of VEGF receptor 2 which is involved in numerous macular diseases.

    A phase I/II clinical trial completed in 2019 and demonstrated tolerability of the treatment. No new clinical trials have been registered.

    GS030 [GENE] [GA]

    GS030, developed by GenSight, is a gene vector that delivers a photosensitive protein gene into the eye, using the same technology used by Adverum for ADVM-022, combined with goggles to enhance visual signals.

    The phase I/II PIONEER study is under way in patients with retinitis pigmentosa. Three doses are being evaluated for safety. Initial results are expected early 2022.

    Phase I studies in GA are planned.

    Axitinib intravitreal implant (OTX-TKI) [nAMD]

    OTX-TKI, under development by Ocular Therapeutix, is an extended-release intraocular hydrogel implant containing axitinib, a small molecule that inhibits VEGF receptors and is expected to offer ‘pan-VEGF’ inhibition in multiple macular diseases.

    Phase I clinical trials are ongoing to evaluate safety, tolerability and efficacy of various doses of OTX-TKI. Initial results are expected in late 2022.

    HMR59 [nAMD] [GA]

    HMP59, developed by Hemera Biosciences and Janssen Research & Development, is a gene vector therapy to treat geographic atrophy (atrophic ‘dry’ AMD) and nAMD.

    The treatment delivers a gene for soluble CD59 into the retina by a one-time eye injection. CD59 inhibits activity of the complement system and is expected to product retinal cells from complement-mediated damage.

    A phase I dose escalation study has been completed, and a second long-term safety study is under way.

    ADVM-022 [nAMD]

    ADVM-022, developed by Adverum, is a gene vector that delivers a working copy of the aflibercept gene into the eye, providing continuous long-term treatment. It is expected to be a one-time eye injection.

    In nAMD, the phase I OPTIC study is under way. This study compares two different doses of ADVM-022, with additional aflibercept as required. To date, efficacy and safety appear to be acceptable. Final results are expected in 2022 and a phase II nAMD study is planned.

    Clinical development of ADVM-022 in DMO has been discontinued based on results from the phase II INFINITY study. In May 2021, serious adverse reactions were detected, including eye inflammation and low intraocular pressure.

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