A Randomized Controlled, Double-Masked, Crossover Clinical Trial Designed To Evaluate The Safety And Exploratory Efficacy Of 1.0 Mg Luminate® (Alg-1001) As A Treatment For Non-Exudative Macular Degeneration

To evaluate the safety and exploratory efficacy of 1.0mg of Luminate® in patients with Intermediate Non-Exudative Macular Degeneration

Start Date01 Aug 2017

Sponsor / Collaborator

Allegro Ophthalmics LLC

NCT02435862 / CompletedPhase 2

Protocol PVD-202: A Phase 2, Randomized, Double-Masked, Placebo-Controlled Multicenter Clinical Trial Designed to Evaluate the Safety and Efficacy Study of Luminate® in Inducing PVD in Non-Proliferative Diabetic Retinopathy

A Phase 2, Randomized, Double-masked, Placebo-controlled Multicenter Clinical Trial Designed to Evaluate the Safety and Efficacy of Luminate in Inducing PVD in Subjects with Non-Proliferative Diabetic Retinopathy.

Start Date01 Feb 2015

Sponsor / Collaborator

Allegro Ophthalmics LLC

[+2]

NCT02348918 / CompletedPhase 2

A Phase 2 Randomized, Controlled, Double-Masked, Multicenter Clinical Trial Designed to Evaluate the Safety and Exploratory Efficacy of Luminate® (ALG-1001) as Compared to Avastin® in the Treatment of Diabetic Macular Edema (DME)

A Phase 2 Multi center, Randomized, Controlled, Double-Masked Clinical Trial Designed To Evaluate The Safety And Exploratory Efficacy Of Luminate® (Alg-1001) As Compared To Avastin® In The Treatment Of Diabetic Macular Edema

Start Date13 Oct 2014

Sponsor / Collaborator

Allegro Ophthalmics LLC

[+2]

100 Clinical Results associated with Risuteganib

100 Translational Medicine associated with Risuteganib

100 Patents (Medical) associated with Risuteganib

Literatures (Medical) associated with Risuteganib

01 Mar 2024·Journal of ethnopharmacology

Anti-inflammatory effect and mechanism of active parts of Artemisia mongolica in LPS-induced Raw264.7 cells based on network pharmacology analysis.

Article

Author: Zhu, ZiWei ; Wang, Fangsheng ; Liu, Liu ; Aisa, Haji Akber ; Xin, Xuelei

ETHNOPHARMACOLOGICAL RELEVANCE:

Artemisia mongolica is well known for its use in folk medicine, it is commonly used to alleviate a variety of diseases associated with inflammation, such as laryngitis, tonsillitis, headaches and hepatitis in northwest China. However, its anti-inflammatory mechanism is still unknown.

AIM OF THE STUDY:

The most potential anti-inflammatory part (AMPA) was identified by screening individual parts of A. Mongolica. After the network pharmacological analysis, the anti-inflammation effects and molecular mechanisms of AMPA were evaluated in RAW264.7 cells induced by LPS.

MATERIALS AND METHODS:

AMPA was chosen as the most anti-inflammatory of the A. Mongolica, as measured by the effect of each part of the A. Mongolica on NO and COX-2. The chemical composition of AMPA was identified using HPLC-Q-TOF-MS/MS, and targets of bioactive chemicals and targets related to inflammation were found using open-source databases. The "Compound-targets" network and PPI network were established by combining compounds and overlapped targets, and targets in the PPI networks were analyzed by GO and KEGG enrichment. The RAW26.7 cells induced by LPS were used as a model of inflammation examination. MTT assay was performed to assess the cytotoxicity of AMPA on LPS-induced RAW264.7 cells. The level of NO was measured by the Griess method while the inflammatory factors were detected by ELISA. The protein expression levels of iNOS, COX-2, MAPK, NF-κB signaling pathway and AMPK/Nrf2-related proteins were determined by Western blot. The results of nuclear translocation of p65 and Nrf2 were analyzed by immunofluorescence assay.

RESULTS:

A total of 18 compounds with potential bioactivity were identified, and after intersecting 640 compound-predicted targets and 1608 inflammation targets, the compounds and intersected targets were utilized to structure "compound-target" and PPI networks. Among AMPA, AM6, AM7, AM11, AM8 and AM1 compounds were essential in the "compound-targets" network, meanwhile, TNF, RELA, MAPK1, NOS2, PRKAG, and PTGS2 targets play important roles in the PPI network. The top 10 terms and pathways were obtained based on GO and KEGG. The cell experiments show that 50 μg/mL was the maximum concentration of AMPA without cytotoxicity in the LPS-induced RAW264.7 cell model. When compared with the LPS group, AMPA treatment not only effectively suppressed the generation of NO, TNF-α, IL-6, PGE2, IL-1β and MCP-1 in LPS-induced RAW264.7 cells, but also down-regulated the expression of COX-2, iNOS and the protein levels p-ERK, p-p38, p-IκB-α and p-p65, inhibited the nuclear translocation of p65. Furthermore, the expression levels of p-LKB1, p-AMPK, Nrf2 and HO-1 proteins were up-regulated and Nrf2 nuclear translocation was promoted.

CONCLUSION:

AMPA should be considered an anti-inflammatory agent for the results of network pharmacology and in vitro, which could inhibit the MAPK pathway and NF-κB pathway and activate the AMPK/Nrf2 pathway in LPS-stimulated RAW264.7 cells.

05 Oct 2023·Pharmaceutics

Systemic Dendrimer-Peptide Therapies for Wet Age-Related Macular Degeneration.

Article

Author: Wu, Tony ; Kannan, Rangaramanujam M ; Liu, Chang

Wet age-related macular degeneration (AMD) is an end-stage event in a complex pathogenesis of macular degeneration, involving the abnormal growth of blood vessels at the retinal pigment epithelium driven by vascular endothelial growth factor (VEGF). Current therapies seek to interrupt VEGF signaling to halt the progress of neovascularization, but a significant patient population is not responsive. New treatment modalities such as integrin-binding peptides (risuteganib/Luminate/ALG-1001) are being explored to address this clinical need but these treatments necessitate the use of intravitreal injections (IVT), which carries risks of complications and restricts its availability in less-developed countries. Successful systemic delivery of peptide-based therapeutics must overcome obstacles such as degradation by proteinases in circulation and off-target binding. In this work, we present a novel dendrimer-integrin-binding peptide (D-ALG) synthesized with a noncleavable, "clickable" linker. In vitro, D-ALG protected the peptide payload from enzymatic degradation for up to 1.5 h (~90% of the compound remained intact) in a high concentration of proteinase (2 mg/mL) whereas ~90% of free ALG-1001 was degraded in the same period. Further, dendrimer conjugation preserved the antiangiogenic activity of ALG-1001 in vitro with significant reductions in endothelial vessel network formation compared to untreated controls. In vivo, direct intravitreal injections of ALG-1001 and D-ALG produced reductions in the CNV lesion area but in systemically dosed animals, only D-ALG produced significant reductions of CNV lesion area at 14 days. Imaging data suggested that the difference in efficacy may be due to more D-ALG remaining in the target area than ALG-1001 after administration. The results presented here offer a clinically relevant route for peptide therapeutics by addressing the major obstacles that these therapies face in delivery.

01 Nov 2022·Ophthalmology. Retina

Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry Age-Related Macular Degeneration

Article

Author: Jaffe, Glenn J ; Farsiu, Sina ; Srivastava, Sunil K ; Karageozian, Vicken ; Sarayba, Melvin ; Kaiser, Peter K ; Abraham, Joseph R ; Chiu, Stephanie J ; Loo, Jessica ; Ehlers, Justis P ; Bouckaert, Laurens

OBJECTIVE:

The purpose of the study was to perform a post hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from the completed phase II study in subjects with dry age-related macular degeneration (AMD).

DESIGN:

Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study.

SUBJECTS:

Eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. Patients with concurrent vision-influencing or macula-obscuring ocular pathologies were excluded.

METHODS:

Patients were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. A second 1-mg intravitreal injection of risuteganib was given at week 16 to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT to explore features associated with positive responses to risuteganib.

MAIN OUTCOME MEASURES:

Treatment response was defined as a gain of ≥ 8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib.

RESULTS:

Thirty-nine patients completed the study and underwent analysis. In the treatment arm, 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. In the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib.

CONCLUSIONS:

This post hoc analysis demonstrated that baseline OCT features may help determine the likelihood of a functional response to risuteganib. The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment.

News (Medical) associated with Risuteganib

20 Feb 2024

·www.pharmaceutical-technology.com

Singapore HSA accepts AffaMed’s NDA for ocular treatment

DEXTENZA is a corticosteroid intracanalicular insert designed to be placed into the punctum and canaliculus of the eye. Credit: 4 PM production/Shutterstock.com. The Singapore Health Sciences Authority (HSA) has accepted the new drug application (NDA) for AffaMed Therapeutics’ DEXTENZA (0.4 mg dexamethasone ophthalmic insert) to treat ocular inflammation and pain. The treatment is indicated following ophthalmic surgical procedures and for ocular itching linked to allergic conjunctivitis. This marks a significant milestone for the company as it seeks to expand the reach of DEXTENZA, which is already approved in the US and listed in Macau for similar indications. DEXTENZA is a corticosteroid intracanalicular insert designed to be placed into the punctum and canaliculus of the eye. It offers dexamethasone to the ocular surface for up to 30 days without the use of preservatives. See Also: US FDA accepts review of argenx’s VYVGART Hytrulo for CIDP Iovance’s Amtagvi for melanoma treatment gains FDA approval The insert’s unique feature is its reabsorption, enabling it to exit the nasolacrimal system on its own. AffaMed is progressing the development of DEXTENZA as the first physician-administered, sustained-release intracanalicular insert available to patients in ASEAN countries and Greater China. The convenience of a single administration that delivers a preservative-free dose of dexamethasone over 30 days provides significant benefits over existing therapies, which typically require multiple daily eye-drop applications. The company has also initiated a registrational trial to assess the efficacy and safety of DEXTENZA against a placebo vehicle for treating inflammation and pain post-cataract surgery in mainland China. Topline data from this trial is anticipated in the third quarter of 2024. AffaMed entered a licensing agreement with Ocular Therapeutix in October 2020 in a strategic move to broaden its market. The agreement covers the development and commercialisation of DEXTENZA in South Korea, Greater China and some ASEAN [Association of South East Asian Nations] markets. AffaMed CEO Vijay Karwal stated: “As the first NDA filing by AffaMed, the acceptance of our DEXTENZA NDA in Singapore represents an important milestone in our company’s journey to successfully advance much-needed therapeutic candidates through regulatory pathways across multiple regions in Asia. “DEXTENZA is the lead candidate in AffaMed’s innovative and differentiated ophthalmology pipeline and represents an important advancement in the treatment of ocular inflammation and pain following ophthalmic surgery and ocular itching associated with allergic conjunctivitis.” In September 2023, the company received approval from China’s National Medical Products Administration for a clinical trial application of risuteganib (Luminate ) to treat intermediate dry age-related macular degeneration.

License out/inNDADrug Approval

25 Sep 2023

·www.prnewswire.com

AffaMed Therapeutics Announces Clinical Trial Application Approval in Mainland China for Risuteganib (Luminate®) First-in-Class Candidate for the Treatment of Intermediate Dry AMD

SHANGHAI, Sept. 25, 2023 /PRNewswire/ -- AffaMed Therapeutics ("AffaMed"), a global biotechnology company dedicated to developing and commercializing transformative pharmaceutical, digital and surgical products that address critical unmet medical needs in ophthalmological, neurological and psychiatric disorders, today announced that China's National Medical Products Administration has approved AffaMed's Clinical Trial Application (CTA) to investigate the efficacy and safety of Risuteganib (Luminate®), its First-in-Class, new Mechanism of Action ophthalmic intravitreal injectable product candidate for the treatment of Intermediate Dry Age-related Macular Degeneration (Dry AMD). Under the CTA approval, AM011 is expected to become the first product in China to enter Phase 3 development for the treatment of Dry AMD. In December 2021, AffaMed Therapeutics entered into a licensing agreement with Hanmi Pharmaceutical Co., Ltd. ("Hanmi") for the manufacturing, development and commercialization of Risuteganib (Luminate®) in Greater China (mainland China, Hong Kong, Taiwan and Macau). Dr. Dayao Zhao, CEO of AffaMed commented: " To date there is no approved and effective treatment in China for patients suffering from Dry AMD which represents the vast majority of the AMD patient population. We are encouraged by the Chinese regulator's efficiency in approving our application for this innovative therapy. We are looking forward to bringing this innovative treatment to Dry AMD patients in Greater China as soon as possible." About Dry AMD Age-related macular degeneration (AMD) is a progressive blinding disease that currently affects millions of people worldwide and is the leading cause of blindness in the elderly. Dry AMD accounts for approximately 80-90% of the total AMD patient population. As of 2020, the number of Dry AMD patients in China was estimated at 33.5 million and is projected to exceed 43 million by the end of this decade[1]. There are currently no approved therapies for the treatment of Intermediate Dry AMD. About Risuteganib (Luminate®) In 2015, Hanmi acquired the exclusive rights for intravitreal use from Allegro Ophthalmic LLC, for the development and commercialization of Risuteganib (Luminate®) in Korea and China. Luminate® is a first-in-class integrin regulator with a novel mechanism of action to regulate multiple pathways of oxidative stress response, including mitochondrial dysfunction, which contributes to diseases such as intermediate Dry AMD. Risuteganib (Luminate®) has successfully met the primary endpoint in a Phase 2 proof of concept clinical trial with statistically significant vision improvement in patients with intermediate Dry AMD versus placebo. Allegro has entered into a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration to advance Risuteganib (Luminate®) into a Phase 2b/3 pivotal registration program. About AffaMed Therapeutics AffaMed Therapeutics is a clinical stage biopharmaceutical company focused on developing and commercializing transformative pharmaceutical, digital and surgical products that address critical unmet medical needs in ophthalmological, neurological and psychiatric disorders for patients in Greater China and around the world. The leadership team at AffaMed Therapeutics has gained deep industry expertise and an extensive track record in high-quality discovery, clinical development, regulatory affairs, business development, manufacturing, and commercial operations at leading multi-national biopharmaceutical companies in China and globally. About Hanmi Pharmaceuticals Hanmi Pharmaceutical, founded in 1973, is an R&D-oriented biopharmaceutical company representing Korea. After the establishment by Pharmacist Lim Sung-ki, it was converted into a holding company system in 2010 and incorporated into a subsidiary of Hanmi Science. Hanmi Pharmaceutical invests more than 15% of its sales in R&D every year and is developing 26 drug candidates for innovative new drugs in three major fields; 1) Biologics: LAPSCOVERY platform applied long-acting pipeline; 2) NCE: Primarily oncology and auto-immune disease targeted pipelines; and 3) Fixed-dose combination programs. Hanmi Pharmaceutical's representative new drug target diseases include metabolic diseases such as obesity, rare diseases, and various types of cancer. In addition, Hanmi Pharmaceutical operates production facilities ranging from raw materials to chemicals and biopharmaceuticals and has more than 5,000 employees in Korea and China. SOURCE AffaMed Therapeutics Ltd.

Phase 2License out/inClinical Result

13 Apr 2023

·www.prnewswire.com

Allegro Ophthalmics Receives FDA Agreement Under Special Protocol Assessment (SPA) for Phase 2b/3 Clinical Trial of Risuteganib for the Treatment of Intermediate Dry AMD

- Intermediate Dry AMD Treatment Is a Significant Unmet Need - Mitochondrial Stabilizing Candidate Risuteganib Has Shown Best Corrected Visual Acuity Gains in Dry AMD Patient Population Allegro Ophthalmics, LLC, a privately held biopharmaceutical company focused on the development of novel mitochondrial stabilizers for the treatment of ocular diseases, today announced that the Company has received agreement from the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the design of its Phase 2b/3 clinical trial of risuteganib (Luminate®) for the treatment of intermediate, non-exudative age-related macular degeneration (dry AMD). Finalization of this assessment indicates that the FDA agrees that critical elements of the overall protocol design (e.g., entry criteria, dose selection, endpoints, and planned analyses) are adequate and acceptable for a study intended to support a future marketing application. "We are excited that the overall protocol design of our Phase 2b/3 dry AMD clinical trial was finalized by the FDA," said Vicken Karageozian, M.D., President and CEO of Allegro Ophthalmics, LLC. "The agreement by the FDA of the SPA provides a clear regulatory path for our first-in-class drug, risuteganib, for the treatment of intermediate dry AMD for an unmet medical need. This is important because dry AMD leads to irreversible, and in many cases catastrophic, vision loss. A therapy to treat this disease is greatly needed." The agreement by the FDA of the SPA provides a clear regulatory path for risuteganib for intermediate dry AMD. The Phase 2b/3 study design is based on Allegro's successfully completed U.S. Phase 2a study, in which the primary endpoint was the proportion of subjects with a gain of ≥ 8 letters of vision with two risuteganib injections versus one sham treatment. The Phase 2a trial was a prospective, randomized, double masked, placebo-controlled, multi-center U.S. study that evaluated the safety and efficacy of risuteganib in patients with intermediate dry AMD. The primary endpoint was met, with 48 percent of patients in the risuteganib arm at week 28 and 7 percent of patients in the sham group at week 12 gaining ≥ 8 letters from baseline (p=0.013). Risuteganib was found to be safe, with no reported drug related serious adverse events (SAEs). Additional findings that support the visual acuity improvement included improvements in retinal sensitivity (microperimetry) and color vision (Lanthony color test). The Phase 2b/3a study will evaluate efficacy at 52 weeks and safety through 96 weeks. Patients will receive 5 intravitreal injections (IVTs) 12 weeks apart with continued IVT treatment during the follow-up safety portion of the study. The primary endpoint of the study is the improvement in best corrected visual acuity (BCVA) at 52 weeks in the active risuteganib group vs the sham control group. This study design also includes threshold OCT screening, such as minimum ellipsoid zone and photoreceptor layer thickness, that strongly predicts BCVA response to treatment, thus helping clinicians predict outcomes and select the patients most likely to benefit from treatment. About Allegro Ophthalmics, LLC Allegro Ophthalmics, LLC is a privately held biopharmaceutical company focused on the development of novel oxidative stress stabilizers for the treatment of ocular diseases. Pre-clinical data suggest that risuteganib (Luminate®), Allegro's lead investigational compound in retina, may simultaneously act on the angiogenic, inflammatory and mitochondrial metabolic pathways implicated in diseases, such as dry AMD. A U.S. Phase 2a study with risuteganib in less advanced dry AMD met its primary endpoint of vision recovery. Expanding its oxidative stress-stabilizing portfolio, Allegro developed ALG-1007 for topical use in dry eye disease. ALG-1007 demonstrated promising results in two ex-U.S. studies in humans. For more information, visit www.allegroeye.com. SOURCE Allegro Ophthalmics

Clinical Result

100 Deals associated with Risuteganib

External Link

KEGG	Wiki	ATC	Drug Bank
D11436	-	-	DB14911

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
dry age-related macular degeneration	Phase 3	-	Hanmi Pharmaceutical Co., Ltd.	30 Jan 2022
Wet Macular Degeneration	Phase 2	MX	Allegro Ophthalmics LLC	17 Aug 2016
Nonproliferative diabetic retinopathy	Phase 2	US	Allegro Ophthalmics LLC	01 Feb 2015
Peripheral Vascular Diseases	Phase 2	US	Allegro Ophthalmics LLC	01 Feb 2015
Vitreomacular Adhesion	Phase 2	US	Allegro Ophthalmics LLC	01 Feb 2014
Wet age-related macular degeneration	Phase 2	MX	Allegro Ophthalmics LLC	01 Mar 2012
Diabetic macular oedema	Phase 2	MX	Allegro Ophthalmics LLC	01 Jan 2011
Retinal Diseases	Phase 2	-	Allegro Ophthalmics LLC	-
Retinitis Pigmentosa	Phase 1	KR	Hanmi Pharmaceutical Co., Ltd.	31 Dec 2018

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03626636 (Pubmed) Manual	Phase 2	Age Related Macular Degeneration	39	risuteganib	rrysozaiex(lgbnsvvbvd) = qrcerynqeh wsxaeocgco (gpksraeqgs ) View more	Positive	01 Aug 2022
				sham injection	rrysozaiex(lgbnsvvbvd) = jjgsirxugw wsxaeocgco (gpksraeqgs ) View more
NCT03626636 (Pubmed \| Ophthalmic Surg Lasers Imaging Retina) Manual	Phase 2	Age Related Macular Degeneration	45	risuteganib	girzkpqmyf(mmyemqupks) = frbgqzmyla vabbkedevg (mvahkmiqlw ) View more	Positive	01 Jun 2021
				sham injection	girzkpqmyf(mmyemqupks) = pozxmjqijm vabbkedevg (mvahkmiqlw ) View more
AAO2020	Phase 2	Age Related Macular Degeneration	-	Risuteganib 1.0mg	rgcurhgntr(xyyjpkvobk) = nonmrrbspz dhebkoicei (aftyceqlkp )	-	13 Nov 2020
				Risuteganib	rgcurhgntr(xyyjpkvobk) = lxgqimywxu dhebkoicei (aftyceqlkp )
Phase 2 study (ARVO2020)	Phase 2	Wet age-related macular degeneration	-	Risuteganib 1.0mg	lqtjupwfts(gaaafxbdsr) = qtzaiwoyef lonvkgovse (sqiowdlqxd ) View more	Positive	01 Jun 2020
				Risuteganib	lqtjupwfts(gaaafxbdsr) = jbjjaecvwr lonvkgovse (sqiowdlqxd )
NCT02348918 (CTgov)	Phase 2	Diabetic macular oedema	218	Luminate 1.0mg (Luminate 1.0mg Group)	gsiyyazipm(yguhtljkkz) = sebapysekz dwqfpuvood (fufmjgrhrz, shqlfcnpmn - bjufrwfvqm) View more	-	07 Dec 2018
				Luminate 2.0mg (Luminate 2.0mg Group)	gsiyyazipm(yguhtljkkz) = ckkthaxurn dwqfpuvood (fufmjgrhrz, qlctwvbvuv - lrivspajfz) View more
ARVO2018	Not Applicable	stress oxidative	-	ALG-1001 peptide	irngwxhmro(mwjpsguolc) = ynsmzgazst kppkaxipht (frwphythqg ) View more	-	01 Jul 2018

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