G6PC1

Treatment with DTX401 resulted in a statistically significant reduction in daily cornstarch intake at Week 48 (p Company will host investor call today at 5:00 p.m. ET May 30, 2024 -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced positive topline results from the Phase 3 GlucoGene study (NCT05139316) evaluating DTX401, an investigational gene therapy for the treatment of patients aged eight years and older with glycogen storage disease type Ia (GSDIa). The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p “This is an incredible milestone for the DTX401 program. These clinically important and statistically significant results are consistent with our Phase 1/2 findings, and the continued improvement in these treated patients reflects the acquired ability to break down glycogen as a source of endogenous glucose from their treated livers,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We want to thank the patients, families and treating community for their ongoing participation in this study and their support of progress for the broader GSDIa community.” The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48. Treatment with DTX401 resulted in a mean reduction of 1.1 cornstarch doses per day in the DTX401 treatment group compared with a mean reduction of 0.2 in the placebo group (p=0.0011). Patients in the DTX401 group also showed significant improvement in both frequency and quantity of nighttime cornstarch dosing compared with the placebo group. This blinded study established non-inferiority (p The Patient Global Impression of Change (PGIC) at Week 48 showed a median score of 2.0 (moderately improved) for the DTX401 treatment group and 1.0 (minimally improved) for the placebo group (p=0.132). Moderately or higher improved PGIC scores correlated with a ≥30% reduction in total daily cornstarch intake indicating that this is a clinically meaningful threshold for patients. “With these Phase 3 results, the significant reduction in cornstarch intake with continued management of glucose control has the potential to offer meaningful benefit to patients while improving their quality of life on a daily basis,” stated Rebecca Riba-Wolman, M.D., director of the Glycogen Storage Disease Program & Disorders of Hypoglycemia at Connecticut Children’s Medical Center/University of Connecticut Medical School and study investigator. “GSDIa is a disease that never takes a break, where you must constantly think about your own, or your child's, safety and risk of severe low blood sugar and acidosis throughout the day and especially at night. A treatment that can improve these daily concerns for people with GSDIa without significant risks is essential.” The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. Anticipated vector-induced hepatic effects were all non-serious and manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity or thrombotic microangiopathy were observed in the study through Week 48. Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year. These results will be discussed with regulatory authorities to support a marketing application in 2025. Ultragenyx recently presented long-term DTX401 Phase 1/2 data demonstrating durable response, with sustained, clinically meaningful reductions in cornstarch lasting up to 5 years in patients treated with open-label DTX401 as of the data cut-off. All 12 patients in the study have been followed for an average of 4 years and continue to demonstrate improved glucose control, with a mean total daily reduction of cornstarch intake of 72% (p<0.0001) from baseline to their last available timepoint. The 48-week randomized, double-blind, placebo-controlled study treated 46 patients aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose measured by ddPCR) or placebo. There were 44 patients in the modified intention-to-treat (mITT) population with efficacy data within the Week 48 analysis period following treatment with DTX401 (n=20) or placebo (n=24). At Week 48, eligible patients crossed over and received the alternate treatment. After crossover, patients will be followed for an additional 96 weeks. After study completion, patients will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post-DTX401 infusion. GSDIa is a serious inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies. An estimated 6,000 patients worldwide are affected by GSDIa. DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon and cortisol. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted orphan drug designation, regenerative medicine advanced therapy (RMAT) designation and Fast Track designation from the U.S. FDA, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency. Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease. The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency. The content above comes from the network. if any infringement, please contact us to modify.

DUBLIN--( BUSINESS WIRE )--The "AAV vectors in gene therapy - Pipeline Insight, 2022" drug pipelines has been added to ResearchAndMarkets.com's offering. AAV vectors in gene therapy: Overview Out of the several viral vectors that have been used to date for delivering the genes of interest, the Adeno-associated viral (AAV) vector appears to be the safest and effective vehicle and can maintain long-term gene and protein expression following a single injection of the vector. AAV vectors are the leading viral vectors for gene delivery to treat a variety of human diseases. Recent advances in developing clinically desirable AAV capsids, optimizing genome designs, and harnessing revolutionary biotechnologies have contributed extensively to the growth of the gene therapy field. AAV Vectors in Gene Therapy Emerging Drugs GS010: Gensight Biologics LUMEVOQ (GS010; lenadogene nolparvovec) targets Leber Hereditary Optic Neuropathy (LHON) by leveraging a mitochondrial targeting sequence (MTS) proprietary technology platform, arising from research conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus). The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function. "LUMEVOQ" was accepted as the invented name for GS010 (lenadogene nolparvovec) by the European Medicines Agency (EMA) in October 2018. Valoctocogene roxaparvovec: BioMarin Pharmaceutical Valoctocogene roxaparvovec is an investigational AAV5 gene therapy under regulatory review for the treatment of severe hemophilia A. It is currently in preregistration stage of development. In June 2021, BioMarin resubmitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA). In the United States, BioMarin intends to submit two-year follow-up safety and efficacy data on all study participants from the Phase III GENEr8-1 study to support the benefit/risk assessment of valoctocogene roxaparvovec, as previously requested by the Food and Drug Administration (FDA). BioMarin is targeting a Biologics License Application (BLA) resubmission in the second quarter of 2022, assuming favorable study results, followed by an expected six-month review by the FDA. DTX401: Ultragenyx Pharmaceutical DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-? under control of the native promoter. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-? activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. In a Phase I/II clinical study, all nine patients showed a clinical response, with significant reductions in the need for cornstarch and improvements in glucose control and other metabolic parameters compared to baseline. The drug is currently being evaluated in Phase III clinical trial to treat patients with Glycogen storage disease type I. AAV5-RPGR: MeiraGTx AAV-RPGR is an investigational gene therapy for the treatment of patients with X-linked retinitis pigmentosa (XLRP) caused by disease-causing variants in the eye specific form of the RPGR gene (RPGR ORF15). AAV-RPGR is designed to deliver functional copies of the RPGR gene to the subretinal space in order to improve and preserve visual function. MeiraGTx and development partner Janssen are currently conducting a Phase III clinical trial of AAV-RPGR in patients with XLRP with disease-causing variants in RPGR ORF15. Timrepigene emparvovec: Biogen Timrepigene emparvovec is an AAV2 vector administered by subretinal injection, which aims to provide a functioning CHM gene and expression of the REP-1 protein to restore membrane trafficking and thereby slow, stop or potentially reverse decline in vision. Data from the Phase 1/2 studies demonstrated a slower rate of decline in visual acuity in patients treated with timrepigene emparvovec compared to untreated patients in the natural history study. In addition, some patients treated with timrepigene emparvovec showed improvements in visual acuity. The studies also demonstrated that timrepigene emparvovec was generally well tolerated with an acceptable safety profile. The safety and efficacy of a single subretinal injection of timrepigene emparvovec is currently being evaluated in the ongoing Phase III STAR study. AMT 061: UniQure AMT-061 (etranacogene dezaparvovec) is an experimental gene therapy that uniQure is developing to treat hemophilia B. AMT-061 uses a modified and harmless adeno-associated virus 5 (AAV5) to deliver a highly functional copy of the F9 gene, called FIX-Padua, to patients' cells. The FIX-Padua gene version was shown to result in FIX clotting activity eight times greater than that associated with the standard F9 gene. As such, the one-time therapy - administrated directly into the bloodstream - is expected to increase FIX levels, helping to prevent and control bleeds. If approved, the therapy will be marketed globally by CSL Behring, which closed a commercialization and licensing agreement with uniQure in May 2021. UniQure and CSL Behring expect to file a regulatory application to the U.S. Food and Drug Administration (FDA) in early 2022 seeking AMT-061's approval for hemophilia B. Research and Development. RGX-314: REGENXBIO RGX-314 is being investigated as a potential one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal conditions. RGX-314 consists of the NAV AAV8 vector, which encodes an antibody fragment designed to inhibit vascular endothelial growth factor (VEGF). RGX-314 is believed to inhibit the VEGF pathway by which new, leaky blood vessels grow and contribute to the accumulation of fluid in the retina. REGENXBIO is advancing research in two separate routes of administration of RGX-314 to the eye, through a standardized subretinal delivery procedure as well as delivery to the suprachoroidal space. REGENXBIO has licensed certain exclusive rights to the SCS Microinjector from Clearside Biomedical, Inc. to deliver gene therapy treatments to the suprachoroidal space of the eye. According to the company's pipeline, the drug is currently in the Phase III stage of development. SPK-8011: Spark Therapeutics Investigational SPK-8011, a novel bio-engineered adeno-associated viral (AAV) vector utilizing the AAV-LK03 capsid, also referred to as Spark200, contains a codon-optimized human factor VIII gene under the control of a liver-specific promoter. The Food and Drug Administration (FDA) granted orphan-disease designation and breakthrough therapy designation in the US, while the European Commission has granted orphan designation to SPK-8011. NFS-01: Neurophth Investigational NR082, a novel recombinant adeno-associated viral serotype 2 vector (rAAV2) containing a codon-optimized of NADH-dehydrogenase subunit 4 (ND4) gene under the control of the cytomegalovirus promoter and enhancer, is a novel ophthalmic injection that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND4 mutations. It is currently being evaluated in Phase II/III clinical trial. GT 005: Gyroscope Therapeutics GT005 is designed as an AAV2-based one-time investigational gene therapy for GA secondary to AMD that is delivered under the retina. GT005 aims to restore balance to an overactive complement system, a part of the immune system, by increasing production of the CFI protein. Complement overactivation has been strongly correlated with the development and progression of AMD. The CFI protein regulates the activity of the complement system. It is believed that increasing CFI production could dampen the system's overactivity and reduce inflammation, with the goal of preserving a person's eyesight. Gyroscope is also evaluating GT005 in two Phase II clinical trials. Further product details are provided in the report AAV vectors in gene therapy: Therapeutic Assessment This segment of the report provides insights about the different AAV vectors in gene therapy drugs segregated based on following parameters that define the scope of the report, such as: Major Players in AAV vectors in gene therapy There are approx. 70+ key companies which are developing the therapies for AAV vectors in gene therapy. The companies which have their AAV vectors in gene therapy drug candidates in the most advanced stage, i.e. Preregistration include, BioMarin Pharmaceutical. Phases The publisher's report covers around 235+ products under different phases of clinical development like Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Key Players BioMarin Pharmaceutical Gensight Biologics PTC therapeutics Ultragenyx Pharmaceutical MeiraGTx Pfizer Biogen uniQure Pfizer Ultragenyx Pharmaceutical REGENXBIO Biogen Spark therapeuics (Roche) Sarepta therapeutics Neurophth Therapeutics LYSOGENE Gyroscope Therapeutics Nanoscope Therapeutics Homology medicines Ultragenyx Pharmaceutical Passage Bio Freeline therapeutics Astellas Pharma Aspa therapeutics Adrenas Therapeutics ESTEVE Sio Gene Therapies Amicus therapeutics 4D Molecular therapeutics Taysha Gene Therapies Atsena Therapeutics BioMarin Pharmaceutical Abeona Therapeutics REGENXBIO uniQure Taysha Gene Therapies Asklepios BioPharmaceutical Sarepta Therapeutics Abeona Therapeutics Forge Biologics Sangamo therapeuics Bayer LogicBio therapeutics Solid Biosciences Applied Genetic Technologies Spark therapeuics (Roche) Eli lilly and company Lexeo Therapeutics Spark therapeutics Gensight Biologics Alcyone Lifesciences MeiraGTx Audentes therapeutics Vivet Therapeutics Takeda Astellas Gene Therapies Homology Medicines Adverum Biotechnologies Libella Gene Therapeutics Rocket Pharmaceuticals Brain Neurotherapy Bio, Inc. Ocugen Asklepios BioPharmaceutical Neurogene Jaguar Gene Therapy, LLC Axovia Therapeutics Coave therapeutics Novartis/ Arctos medical Novartis/Vedere Bio REGENXBIO Inc. StrideBio Abeona therapeutics Sanofi/ Sirion therapeutics Capsida Biotherapeutics Kriya therapeutics Neurophth Poseida Therapeutics, BridgeBio Pharma DiNAQOR/ Biomarin ViGeneron AskBio/Selecta Biosciences Prevail therapeutics Intas Pharmaceuticals Tenaya Therapeutics Scout Bio therapeutics Ocugen Oyster Point pharmaceuticals Cyprium Therapeutics Solid Biosciences Amicus Therapeutics Coave therapeutics AvantiBio Voyager Therapeutics/ Pfizer Aruvant Sciences Alcyone Lifesciences Gene Therapy Research Institution Co., Ltd. For more information about this drug pipelines report visit https://www.researchandmarkets.com/r/ylu69s .

A potential treatment for Glycogen Storage Disease The Glycogen Storage Disease Program at Connecticut Children’s and UConn Health reported success in a Phase I/II trial of a gene therapy for GSD-Ia. A potential treatment for Glycogen Storage Disease is on its way. (Spencer Platt/Getty Images) The Glycogen Storage Disease Program at Connecticut Children’s and UConn Health reported success in a Phase I/II trial of a gene therapy for GSD-Ia. Glycogen Storage Disease Type Ia (GSD-Ia) is a metabolic disease in which the liver is unable to break down glycogen into glucose. This causes blood sugar levels to plummet. It can damage the kidneys and liver, with serious side effects, including death. In order to prevent seizures and death, patients drink a cornstarch and water solution every couple of hours, but they can’t miss a dose by even 15 minutes. Dr. Rebecca Riba-Wolman, director of the Glycogen Storage Disease Program, and a member of the Division of Pediatric Endocrinology at Connecticut Children’s said, “The participants of the Phase I/II trial overall have seen a 70% decrease in cornstarch needs. Some participants who could previously not go more than four hours without cornstarch are now able to last from 12-15 hours, significantly changing their lives.” What is the Cause of Glycogen Storage Disease? Glycogen Storage Disease Type Ia is caused by a defective gene for the enzyme glycose-6-phosphatase (G6Pase). The gene therapy is developed with Ultragenyx and is dubbed DTX401. It is an investigational AAV8 gene therapy engineered to deliver stable expression and activity of G6Pase-alpha using a single intravenous infusion. The UConn and Connecticut Children’s program was initiated by Dr. David Weinstein, who left to become Vice President, Clinical Development for PassageBio, which focuses on central nervous system disease. “Dr. Weinstein left me with an incredible team of people and I couldn’t do this without them,” Dr. Riba-Wolman said. “Including co-principal investigator Dr. Karen Loechner, and nurses with GSD and ICU experience, the team also includes a metabolic dietician, Malaya Mount, who monitors the participant’s diet and cornstarch intake based on the data from their glucose monitor.” On January 18, 2022, the inpatient clinical trial unit at UConn John Dempsey Hospital infused the first Glycogen Storage Disease patient in the Phase III trial of the gene therapy. In the study, 50% of participants will receive the therapy, and 50% will receive a placebo. It is blinded and is planned to last two years. After the first year, depending on the success of the therapy, anyone who received the placebo will be shifted to gene therapy. The first participant in the trial was first diagnosed at the age of five months. The patient is now a young adult and, instead of a water-corn starch solution, takes Glycosade, which was approved by the U.S. Food and Drug Administration (FDA) in 2012. It is a “superstarch” that maintains blood sugar levels for seven to eight hours overnight. Dr. Juan C. Salazar, Physician-in-Chief, Connecticut Children’s and Department Chair of Pediatrics at UConn School of Medicine, said, “This is very exciting. It’s a culmination of over 20 years of research initiated by our colleague Dr. David Weinstein, who was the visionary and who had the lasting capacity to move this from an idea to the animal model to trial that we are now in, Phase III, and closer to bringing this innovative, life-changing gene therapy to the broader Glycogen Storage Disease community. To me, this is very exciting that together, UConn Health, the Department of Pediatrics at the UConn School of Medicine, in partnership with Connecticut Children’s, are able to be the first in the world to move to the next phase of the trial.”