GUCY2D

FRIDAY, Sept. 6, 2024 -- Gene therapy may restore vision to children and adults robbed of their sight by a rare inherited condition called Leber congenital amaurosis, researchers report. The illness is caused by mutations in the GUCY2D gene, which is critical to producing proteins that enable vision. People with this form of Leber congenital amaurosis (LCA1) typically lose their vision in early childhood. Just under 100,000 people are thought to be affected worldwide. However, a team of researchers at the University of Pennsylvania say that a new gene therapy injected under the retinas of children and adults with LCA1 improved vision by 100 to 10,000 times. “Even though we previously predicted a large vision improvement potential in LCA1, we did not know how receptive patients’ [eye] photoreceptors would be to treatment after decades of blindness,” noted study co-lead author Artur Cideciyan , a research professor of ophthalmology at the university. “It is very satisfying to see a successful multi-center trial that shows gene therapy can be dramatically efficacious.” The findings were published Sept. 5 in The Lancet journal. A total of 15 LCA1 patients -- 12 adults and three children -- participated in the new trial. All had vision that was equal to or below 20/80, meaning that objects a normally sighted person could see at 80 feet could only be clear at 20 feet away for a person with LCA1. Glasses were of little help, because glasses only address the eye's focusing ability, not any underlying medical cause driving vision loss. The new gene therapy is called ATSN-101 and was developed by Atsena Therapeutics, which funded the new trial. This was a small phase 2 trial, meant to gauge a treatment's safety and explore differences when various dosages are used. The injected therapy was tried at three different dosages. Three adult patients each received low, medium and high doses of ATSN-101. Once the treatments' safety was assessed, six participants (including the three children) received high-dose ATSN-101. According to the research team, vision began to improve quickly in all patients, usually within a month of treatment. Improvements have lasted for at least a year. Patients' vision was tested in various ways, including their ability to move through a sometimes dimly-lit pathway, eye charts and "light flash" tests conducted in a dark environment. Two of nine patients who got the high-dose treatment had a 10,000-fold improvement in their sight, Cideciyan's group reported. “That 10,000-fold improvement is the same as a patient being able to see their surroundings on a moonlit night outdoors as opposed to requiring bright indoor lighting before treatment,” said Cideciyan, who also co-directs the Center for Hereditary Retinal Degenerations at UPenn. “One patient reported for the first time being able to navigate at midnight outdoors only with the light of a bonfire.” Side effects could happen, and were usually related to the surgery used to implant the gene therapy. These included tiny hemorrhages within the eye that later healed, or transient inflammation of the eye, treated with steroids. The patients' vision is being tracked going forward, the researchers said, and a bigger, randomized trial is being planned as a requirement of any U.S. Food and Drug Administration approval of the new therapy. The new work follows on the team's prior success using gene therapy to reverse another form of Leber congenital amaurosis, this time connected to a mutation in the CEP290 gene. “The treatment success in our most recent clinical trials together with our earlier experience brings hope for a viable treatment for about 20 percent of infantile blindness caused by inherited retinal degenerations,” study co-author Dr. Tomas Aleman said in a UPenn news release. He is research professor in ophthalmology and co-director of the Center for Hereditary Retinal Degenerations. “The focus now is on perfecting the treatments and treating earlier manifestations of these conditions once safety is confirmed," he said. "We hope similar approaches will lead to equally positive outcomes in other forms of congenital retinal blindness.” Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

First time patients with LCA1 have been treated with gene therapy ATSN-101 demonstrated durable, clinically significant improvements in vision at the high dose and was well-tolerated 12 months post-treatment in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D DURHAM, N.C., Sept. 05, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced that 12-month safety and efficacy data from Atsena’s Phase I/II clinical trial evaluating the investigational gene therapy ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) were published in The Lancet. ATSN-101 was originally developed by Atsena’s founders, Shannon and Sanford Boye at the University of Florida, and is the first gene therapy being studied to treat patients with LCA1. “There are no approved treatments for LCA1, an inherited retinal disease that affects the retina and causes severe vision impairment or blindness in infancy,” said Artur Cideciyan, PhD, Research Professor of Ophthalmology at the Scheie Eye Institute of the University of Pennsylvania and senior author of the paper. “The improvements in visual function and tolerability we saw at the high dose of ATSN-101 at 12 months post-treatment in the ongoing Phase I/II trial support a future randomized, controlled Phase III trial to further evaluate this subretinal gene therapy in patients with LCA1. ATSN-101 represents a significant advancement in the reversal of blindness that begins in childhood.” All 15 enrolled patients with genetically confirmed LCA1 received unilateral subretinal injections to determine the safety and preliminary efficacy of ascending doses of ATSN-101. Thirteen of the patients were treated at the Scheie Eye Institute. Two were treated at the Oregon Health & Science University (OHSU) Casey Eye Institute, under the guidance of Paul Yang, MD, PhD, and Andreas Lauer, MD. In the dose escalation phase, three adult cohorts (n=3 each) were treated with three ascending doses: 1.0E10 vg/eye (low dose), 3.0E10 vg/eye (mid dose), and 1.0E11 vg/eye (high dose). In the dose expansion phase, one adult and one pediatric cohort (n=3 each) were treated at the high dose. The primary endpoint of the Phase I/II clinical trial is the incidence of treatment-emergent adverse events (TEAEs), and secondary endpoints include full-field stimulus test (FST) and best-corrected visual acuity (BCVA). A multi-luminance mobility test (MLMT) was also performed. “This is the first time patients with LCA1 have been treated with gene therapy, making this promising treatment potentially the first-ever gene therapy for this inherited retinal disease,” said Paul Yang, MD, PhD, Associate Professor of Ophthalmology in the OHSU School of Medicine and lead author of the paper. “We are excited to have these results published in The Lancet, a top-tier medical journal, which helps broaden the reach of the important work underway at Atsena to the wider medical community.” For high-dose subjects, mean change in dark-adapted FST was 20.3 decibels, representing a 100-fold improvement for treated eyes. Improvements were first observed at day 28 and persisted over 12 months (p = 0.012). Modest improvements in BCVA were also observed with an average improvement of -0.16 logMAR or 8 letters 12 months post-treatment for high-dose subjects (p = 0.10). Three of six high-dose subjects that performed MLMT achieved the maximum score in the treated eye at Month 12. All adverse events were either mild (91%) or moderate (9%) in severity, and TEAEs (including serious adverse events) were similar to those reported in previous subretinal gene therapy studies. No serious TEAEs were related to ATSN-101, and the majority of TEAEs were related to the surgical procedure. Ocular inflammation was mild and reversible with steroid treatment. “The preliminary efficacy and robust safety data from our ongoing Phase I/II trial underscore the potential of ATSN-101 to be a first-in-class gene therapy for LCA1. It is encouraging that improvements in retinal sensitivity were observed as early as 28 days post-treatment and persisted over at least 12 months, highlighting the durability of our investigational gene therapy,” said Kenji Fujita, MD, Chief Medical Officer of Atsena Therapeutics and co-author of the paper. “We are thrilled that the 12-month data have been published for the first time in this prestigious medical journal.” The published manuscript, titled “Safety and Efficacy of ATSN-101 in Patients with Leber Congenital Amaurosis caused by Biallelic Mutations in GUCY2D : A Phase 1/2, Multi-Center, Open-Label, Unilateral Dose Escalation Study,” is available online and will appear in the print issue of The Lancet at a later date. About GUCY2D -associated Leber congenital amaurosis (LCA1) LCA1 is a monogenic eye disease that disrupts the function of the retina. It is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D -LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this group of inherited retinal diseases. There are currently no approved treatments for LCA1. About ATSN-101 ATSN-101 is an investigational, subretinal AAV5 gene therapy being evaluated in an ongoing Phase I/II clinical trial for Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). ATSN-101 was originally developed at the University of Florida and introduces functional human GUCY2D to photoreceptors. At 12 months post-treatment, ATSN-101 has demonstrated durable, clinically meaningful improvements in vision at the high dose and is well-tolerated. Atsena has received Rare Pediatric Disease designation, Regenerative Medicine Advanced Therapy designation, and Orphan Drug designation from the U.S. Food and Drug Administration for ATSN-101 for the treatment of GUCY2D -associated LCA1. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing best-in-class treatments for the reversal or prevention of blindness from inherited retinal diseases. The company’s lead program is evaluating ATSN-201 in an ongoing Phase I/II clinical trial for X-linked retinoschisis (XLRS), a progressive genetic condition affecting boys and men that is typically diagnosed in childhood. Another ongoing Phase I/II clinical trial is evaluating ATSN-101 for Leber congenital amaurosis type 1 (LCA1), one of the most common causes of blindness in children. Atsena’s pipeline is powered by novel adeno-associated virus (AAV) technology tailored to overcome the hurdles presented by inherited retinal diseases. Founded by pioneers in ocular gene therapy, Atsena is led by an experienced team dedicated to addressing the needs of patients with vision loss. For more information, please visit . Media Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com Business Contact: info@atsenatx.com

DURHAM, N.C., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation to ATSN-101, the company’s investigational gene therapy being evaluated in an ongoing Phase I/II clinical trial in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). The FDA previously granted Regenerative Medicine Advanced Therapy (RMAT) designation and orphan drug designation to ATSN-101 for the treatment of LCA1. RPD designation is granted by the FDA for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a Biologics License Application for ATSN-101 for the treatment of LCA1 is approved by the FDA, Atsena may be eligible to receive a Priority Review Voucher that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. “Rare Pediatric Disease designation is a significant milestone for our LCA1 program as we explore options to advance ATSN-101 into a pivotal clinical trial,” said Patrick Ritschel, MBA, Chief Executive Officer of Atsena Therapeutics. “The FDA designations that have been granted to ATSN-101 not only emphasize the tremendous need for a treatment for patients with LCA1, but also the potential for our subretinal gene therapy to be a major advance in reversing pediatric blindness.” Positive 12-month safety and efficacy data from the company’s ongoing Phase I/II clinical trial of ATSN-101 will be presented at the 47th Annual Macula Society Meeting, which is being held February 7-10, 2024, in Palm Springs, CA. ATSN-101 has demonstrated clinically meaningful improvements in vision at the highest dose and is well-tolerated 12 months post-treatment. Details of the presentation are as follows: Title: Twelve-month safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) Session: Inherited Retinal Dystrophy I (Treatment Trials) Date and Time: Wednesday, February 7, 2024, 6:04 p.m. PST Presenter: Christine Nichols Kay, MD About GUCY2D-associated Leber congenital amaurosis (LCA1) LCA1 is a monogenic eye disease that disrupts the function of the retina. It is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this group of inherited retinal diseases. There are currently no approved treatments for LCA1. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company has two clinical-stage programs, ATSN-201 for X-linked retinoschisis (XLRS) and ATSN-101 for GUCY2D-associated Leber congenital amaurosis (LCA1). ATSN-201, which leverages the company’s novel spreading capsid AAV.SPR, is being evaluated in XLRS patients in a Phase I/II clinical trial known as the LIGHTHOUSE study. The company’s additional proprietary asset is ATSN-301, a dual AAV vector-based gene therapy to prevent blindness from MYO7A-associated Usher syndrome (USH1B). Interim safety and efficacy data from the company’s ongoing Phase I/II clinical trial in patients with LCA1 have demonstrated ATSN-101 is well tolerated and clinically meaningful improvements in vision were observed 12 months post-treatment. Founded by ocular gene therapy pioneers Dr. Shannon Boye and Sanford Boye of the University of Florida, Atsena is based in North Carolina’s Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com. Media Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com Business Contact: info@atsenatx.com