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Exciting results from the latest issue of NEJM: https://lnkd.in/gXJSEkcs.   The article reports on long-term findings from an NIH-sponsored study (a taxpayer-supported study should not sit behind a paywall, but that’s a topic for another day).   The first-in-human, dose-finding study involved the intrathecal administration of an experimental gene therapy in 14 children with a rare inherited neurodevelopmental disorder known as giant axonal neuropathy (GAN).    A few quick takeaways followed by some thoughts below: - Unmet need: There is currently no treatment for GAN, and the disease is usually fatal by 30 years of age. - Novel mechanism of action (MoA) and route of administration (RoA): The gene therapy uses a modified virus to deliver functional copies of the defective GAN gene after being administered directly into the spinal fluid, allowing it to target the motor and sensory neurons affected in GAN. - Encouraging safety:  While 129 treatment-related adverse events (TRAEs) were observed, only one serious AE (fever) was potentially linked to treatment. - (Early) evidence of benefit: At some dose levels, the treatment slowed the rate of motor function decline.  Initial findings suggest regeneration of sensory nerves in some patients.   Encouraging, right?   Well yes, but key commercial strategy questions that must be addressed when considering whether such treatment will ever reach patients beyond the confines of a clinical trial:   What is the ROI one can expect for a novel, possibly game-changing therapy positioned to help only ~2,400 patients in the US/EU?     What are the minimal and optimal Target Product Profiles (TPPs) needed to justify continued investment in this program?   Are gene augmentation products de-risked from a clinical perspective?    Could regulatory incentives help mitigate commercial risk concerns?    Importantly, Taysha (the former industry sponsor) announced late last year that it was discontinuing development of the program, likely for commercial rather than clinical reasons: https://lnkd.in/gPKbED9q).    This was unquestionably a decision not made lightly by Taysha, and it underscores the importance not only of clinical but commercial considerations when allocating scarce investor resources towards the development of life-saving therapies to patients in need.   Such questions must be asked/addressed early in the product lifecycle, ideally before, or at latest shortly after entering the clinic.   We are fortunate to work in an industry built to serve the needs of both its patients AND its shareholders. We press ahead in the face of risk, but our success depends upon mitigating both clinical AND commercial risk. Addressing one without the other is a surefire recipe for failure.    #Ipsos #genetherapy #healthcare

🌟 𝗙𝗗𝗔 𝗔𝗽𝗽𝗿𝗼𝘃𝗲𝘀 𝗘𝗟𝗘𝗩𝗜𝗗𝗬𝗦 𝗚𝗲𝗻𝗲 𝗧𝗵𝗲𝗿𝗮𝗽𝘆 𝗳𝗼𝗿 𝗗𝘂𝗰𝗵𝗲𝗻𝗻𝗲 𝗠𝘂𝘀𝗰𝘂𝗹𝗮𝗿 𝗗𝘆𝘀𝘁𝗿𝗼𝗽𝗵𝘆 (𝗗𝗠𝗗) 🌟 The FDA's recent approval of ELEVIDYS (delandistrogene moxeparvovec-rokl), a gene therapy developed by Sarepta Therapeutics, marks a significant advancement in the treatment of Duchenne muscular dystrophy (DMD). This therapy is specifically designed for children aged 4 to 5 years with a confirmed mutation in the DMD gene. Patient associations highlight the importance of this milestone. As Pat Furlong, CEO of Parent Project Muscular Dystrophy (PPMD), noted, "Today’s decision marks an important moment in gene therapy for patients living with Duchenne. It’s been the lifelong work of so many in the Duchenne community. Our work continues until all patients in our community have access to therapy". The success of ELEVIDYS paves the way for further advancements in gene therapy, highlighting the importance of continued investment  in research for rare diseases. It underscores the potential of gene therapy to address other genetic disorders, offering a glimpse into a future where such innovative treatments could become standard care for a variety of conditions. This milestone fuels optimism among patients and researchers, reinforcing the belief that persistent scientific effort can lead to groundbreaking treatments and improved outcomes for those affected by rare diseases. For more detailed information, you can visit the - https://lnkd.in/eFpyXbFA -  https://lnkd.in/g5d2mqwj #GeneTherapy #DuchenneMuscularDystrophy #DMD #FDAApproval #HealthcareInnovation #RareDiseases #HopeForPatients

FDA expands approval of gene therapy for patients with Duchenne muscular dystrophy FDA has expanded its approval of delandistrogene moxeparvovec-rokl (Elevidys—Sarepta Therapeutics), a recombinant gene therapy, to treat Duchenne muscular dystrophy (DMD). The debilitating disease most often affects males and is characterized by muscle weakness that eventually causes mobility limitations and cardiac or respiratory problems, among other issues. I.V. Elevidys treats the condition by delivering a gene that stimulates production of micro-dystrophin, which contains selected domains of the dystrophin protein found in healthy muscle cells. While the therapy was previously approved only for ambulatory patients aged 4-5 years of age with a confirmed mutation in the DMD gene, the expanded indication includes both ambulatory and non-ambulatory patients aged 4 years and older with a confirmed mutation in the DMD gene. FDA based the decision on trial results submitted by the manufacturer, the life-threatening nature of the disease, and the dearth of effective medical interventions — which it found outweighed the potential risks of the therapy. https://buff.ly/3xwiSk3

Shared by Foundation Fighting Blindness Jul 11, 2024 Retinitis Pigmentosa Research Advances Recent developments in research on retinitis pigmintosa. FDA APPROVES SPARK’S VISION-RESTORING GENE THERAPY Spark Therapeutics’ vision-restoring RPE65 gene therapy has received marketing approval from the U.S. Food and Drug Administration, becoming the first gene therapy to gain regulatory approval in the U.S. for the eye or any inherited condition. Known as LUXTURNA™ (voretigene neparvovec), the gene therapy restored vision in a clinical trial for people between the ages of 4 and 44 with Leber congenital amaurosis (LCA) caused by mutations in the gene RPE65. Study participants with severe vision loss reported putting away their navigational canes, seeing stars, being able to read, and recognizing faces of loved ones. Vision restoration has persisted for at least three years. The treatment is also designed to work for people with retinitis pigmentosa (RP) caused by RPE65 mutations. The Foundation invested about $10 million in more than a decade of lab research that made possible the RPE65 gene therapy clinical trial at the Children’s Hospital of Philadelphia (CHOP). THREE COMPANIES ARE CONDUCTING CLINICAL TRIALS FOR THEIR OPTOGENETIC THERAPIES FOR ADVANCED RP GenSight, Bionic Sight, and Nanoscope have each launched clinical trials for their optogenetic therapies for RP and potentially other retinal diseases. The treatments are designed to provide vision to people who are completely blind from conditions such as retinitis pigmentosa and Usher syndrome. GenSight and Bionic Sight are designed to work by bestowing light sensitivity to ganglion cells in patients who have lost all of their photoreceptors. Nanoscope is targeting bipolar cells. All three companies have reported some modest restored vision in their early stage trials. for more information, please visit https://lnkd.in/d8KVbs3j

FDA expands approval of gene therapy for patients with Duchenne muscular dystrophy FDA has expanded its approval of delandistrogene moxeparvovec-rokl (Elevidys—Sarepta Therapeutics), a recombinant gene therapy, to treat Duchenne muscular dystrophy (DMD). The debilitating disease most often affects males and is characterized by muscle weakness that eventually causes mobility limitations and cardiac or respiratory problems, among other issues. I.V. Elevidys treats the condition by delivering a gene that stimulates production of micro-dystrophin, which contains selected domains of the dystrophin protein found in healthy muscle cells. While the therapy was previously approved only for ambulatory patients aged 4-5 years of age with a confirmed mutation in the DMD gene, the expanded indication includes both ambulatory and non-ambulatory patients aged 4 years and older with a confirmed mutation in the DMD gene. FDA based the decision on trial results submitted by the manufacturer, the life-threatening nature of the disease, and the dearth of effective medical interventions — which it found outweighed the potential risks of the therapy. https://buff.ly/3xwiSk3

A Phase I/II study of Lexeo Therapeutics’ gene therapy to treat patients with Alzheimer’s associated with the APOE4 genetic variant has achieved good interim results according to the company. If approved, this therapy (currently known as LX1001) would be ground-breaking as the first gene therapy for Alzheimer’s disease in a high-risk population with limited treatment options. There are many genes that can influence the risk for Alzheimer’s disease, but one of the most well-known is apolipoprotein E (APOE). The most common allele of the gene is APOE3, which is carried by more than half the population. People with two copies of this allele have a neutral or average risk for Alzheimer’s. However, those with one or more copies of the APOE4 (15–25% of people have one copy) allele are at increased risk and those with one or more copies of APOE2 (5–10% of people have one copy) are at decreased risk of developing the neurodegenerative condition. Since the approval of Biogen’s and Eisai’s Leqembi (lecanemab) in 2023 and Lilly’s Kisunla (donanemab) earlier this year, treatment options for Alzheimer’s are improving. But people with the APOE4 mutation are not eligible for these antibody treatments due to a very high risk of experiencing amyloid-related imaging abnormalities (ARIA) in this patient group. “APOE4 homozygotes are approximately 15 times more likely to develop Alzheimer’s disease than the general population, have faster disease progression, and have an increased risk of ARIA with currently available therapies that can cause serious complications,” said principal study investigator Kim Johnson, MD, division chief, memory disorders at the department of neurology of Duke University School of Medicine, in a press statement.

4DMT’S Gene Therapy for AMD Clears Phase II, Heads to Late-Stage Studies 4D Molecular Therapeutics reported its experimental gene therapy demonstrated a nearly 90% reduction in the need for annualized standard-of-care injections in patients with wet age-related macular degeneration. 4D Molecular Therapeutics announced on Wednesday that its investigational gene therapy 4D-150 demonstrated durable clinical activity in the Phase I/II PRISM study of patients with wet age-related macular degeneration. In a 30-patient cohort, 4D-150 cut the need for standard-of-care injections by 89% through 52 weeks of follow-up, and 70% of these patients were injection-free, according to 4DMT’s announcement. In another cohort of 27 patients with severe disease, the need for standard-of-care treatment dropped by 83% and 44% were injection-free. The gene therapy also resulted in sustained benefits in terms of central subfield thickness and mean best-corrected visual acuity. In terms of safety, PRISM found 4D-150 to be well-tolerated. The frequency for of intraocular inflammation (IOI) was consistent with approved anti-VEGF therapies, which are currently widely used to treat age-related macular degeneration (AMD). Overall, 4DMT documented two IOI episodes in all 71 wet AMD patients enrolled, yielding an incidence rate of 2.8%. There were no cases of retinal artery occlusions, hypotony, vasculitis, choroidal effusions and endophthalmitis related to the gene therapy. https://lnkd.in/d7wgrPWV

Interested in Gene Therapy? Check out our review article, "Gene Therapy for Cardiac Diseases: Methods, Challenges, and Future Directions," recently published in Cardiovascular Research. In this comprehensive review, we explore the latest advancements in molecular approaches—ranging from gene replacement to prime editing—and the various vectors used in cardiac gene therapy. We delve into critical strategies to improve genetic constructs, including promoter engineering, miRNA-regulated genetic cassettes, and systems for conditional expression of siRNAs/mRNAs. Additionally, we address the key factors that could facilitate the clinical translation of cardiac gene therapy, emphasizing research that suggests that even a limited percentage of transduced cardiomyocytes may be enough to halt or reverse the progression of certain cardiac genetic diseases. Our focus throughout the review is the progress of gene therapies for inherited arrhythmia syndromes and genetic cardiomyopathies, conditions for which few effective treatment options currently exist. These life-threatening disorders demand urgent therapeutic innovations. A heartfelt thanks to my mentor, Silvia Giuliana Priori, for her guidance, and to my friends and colleagues, Matteo Gianeselli, MD and Rossana Bongianino, who co-authored the manuscript. https://lnkd.in/dy6-bkDP

Gene Therapies in Ophthalmology are revolutionizing treatment paradigms by directly targeting genetic mutations underlying inherited eye diseases, offering hope for previously untreatable conditions. By delivering functional genes to replace defective ones, these therapies hold immense promise in halting or even reversing vision loss. Companies such as AbbVie/REGENXBIO Inc. (ABBV-RGX-314), GenSight Biologics ( LUMEVOQ), MeiraGTx (Botaretigene sparoparvovec), Johnson & Johnson (JNJ-8120188), Ocugen (OCU400), 4D Molecular Therapeutics (4D-150), and others are spearheading Gene Therapies in Ophthalmology and driving innovation and collaboration, ushering in a new era of sight-saving treatments for patients worldwide. Visit and get a detailed overview of the evolving market landscape of Gene Therapies in Ophthalmology: https://lnkd.in/gujQJ8aM #genetherapy #ophthalmology #visionarysolutions #geneticmedicine #eyehealth #inheritedeyediseases #geneediting #oculargenetics #geneticrevolution #eyecareinnovation #ophthalmicresearch #genemedicine #retinaltherapies #genetech #ophthalmicadvancements #genomicsolutions #eyediseasetreatment #geneticvisioncare

FDA expands approval of gene therapy for patients with Duchenne muscular dystrophy FDA has expanded its approval of delandistrogene moxeparvovec-rokl (Elevidys—Sarepta Therapeutics), a recombinant gene therapy, to treat Duchenne muscular dystrophy (DMD). The debilitating disease most often affects males and is characterized by muscle weakness that eventually causes mobility limitations and cardiac or respiratory problems, among other issues. I.V. Elevidys treats the condition by delivering a gene that stimulates production of micro-dystrophin, which contains selected domains of the dystrophin protein found in healthy muscle cells. While the therapy was previously approved only for ambulatory patients aged 4-5 years of age with a confirmed mutation in the DMD gene, the expanded indication includes both ambulatory and non-ambulatory patients aged 4 years and older with a confirmed mutation in the DMD gene. FDA based the decision on trial results submitted by the manufacturer, the life-threatening nature of the disease, and the dearth of effective medical interventions — which it found outweighed the potential risks of the therapy. https://lnkd.in/gCiuijUv