This study consists of two parts. Part A will evaluate the safety and tolerability of multiple doses of OXB-102 (AXO-Lenti-PD) in participants with Parkinson's disease. Part B will assess the safety and efficacy of the selected dose of OXB-102 in participants with Parkinson's disease.

Start Date17 Oct 2018

Sponsor / Collaborator

Sio Gene Therapies, Inc.

NCT01856439

/ TerminatedPhase 1/2

A Multicentre, Open-label Study to Determine the Long Term Safety, Tolerability and Efficacy of ProSavin in Patients With Bilateral, Idiopathic Parkinson's Disease.

The study is designed to assess the long term tolerability of ProSavin and whether it is safe and efficacious in patients administered ProSavin from the PS1/001/07 study .

Start Date01 May 2011

Sponsor / Collaborator

Axovant Sciences, Inc.

[+1]

NCT00627588

/ CompletedPhase 1/2

A Phase I/II Study of the Safety, Efficacy and Dose Evaluation of ProSavin®, Administered Using Stereotactic Injection to the Striatum of Patients With Bilateral, Idiopathic Parkinson's Disease.

The primary objectives of the trial are to assess the safety and efficacy of ProSavin.
Patients in the trial will have been diagnosed with Parkinson's disease and will be failing on current treatment with L-DOPA but they will not have progressed to drug-induced dyskinesias. The first stage is an open-label dose escalation to evaluate up to three dose levels of ProSavin in cohorts of three patients each. Following a recommendation by the DMC the study may proceed to the second stage of the trial, a further 12 patients will be recruited to confirm efficacy of the optimal dose in the randomized phase of the study.
The efficacy of ProSavin will be assessed using the Unified Parkinson's Disease Rating Score (UPDRS). Patients will be monitored at regular intervals, with the primary endpoint being an efficacy assessment at six months after treatment. The secondary objective of the trial is to asses the extent to which patients' current therapy (L-DOPA) can be reduced following administration of ProSavin.

Start Date01 Jan 2008

Sponsor / Collaborator

Oxford Biomedica Plc

100 Clinical Results associated with AXO Lenti PD(Oxford Biomedica)

100 Translational Medicine associated with AXO Lenti PD(Oxford Biomedica)

100 Patents (Medical) associated with AXO Lenti PD(Oxford Biomedica)

Literatures (Medical) associated with AXO Lenti PD(Oxford Biomedica)

05 Feb 2023·Cureus

A Review of Genetic and Gene Therapy for Parkinson’s Disease

Review

Author: Dumbhare, Omkar ; Gaurkar, Sagar S

Parkinson's disease (PD) is a syndrome with deterioration of neurons, with its onset starting in the '20s, known as the young beginning of Parkinson's to the late inception of the ailment in the 60s. The majority of the environmental risk associated with PD is age. The pathophysiology of PD is related to the accretion of synuclein alpha (SNCA) protein leading to toxicity. This toxicity further leads to a depletion in dopamine levels, creating both motor and non-motor symptoms. PD is the combination of genetic and environmental risk factors. Linkage and association studies provided data on autosomal dominant and recessive genes linked to PD. Current treatment regimes involve using levodopa, catechol-O-methyl transferase inhibitors, anticholinergics, and monoamine oxidase B (MAO-B) inhibitors. Genetic treatment is done by identifying possible targets. Gene therapy includes silencing, replacing, or correcting the flawed gene with a good gene. This therapy has the advantage of eliminating significant PD symptoms with fewer to no adverse effects than conventional treatment. These targets are organized into disease-modifying or non-disease modifying. The distinction between these two is that disease-modifying treatment stops the degeneration of neurons, while non-disease modifying treatment involves dopaminergic enzyme expression. In non-modifying targets, aromatic L-amino acid decarboxylase (AADC) therapy is used but not as a standalone, so the presentation of AADC, tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH) is done together as a tricistronic system. With these developments, a drug named prosavin is under clinical phase 1 trial. Disease-modifying targets involve glial cell-derived neurotrophic factor (GDNF). Direct GDNF delivery reduces PD symptoms. This GDNF infusion technique works with a tetracycline-controlled transactivator. Gene therapy introduction into the treatment of PD would be beneficial as there would be lesser adverse effects seen as linked with conventional treatment involving levodopa, MAO-B inhibitors, and anticholinergics, among a few. This article discusses the genetic basis and genetic model of therapy for PD.

01 Sep 2019·Molecular therapy. Methods & clinical developmentQ2 · MEDICINE

Gene Therapy for Parkinson’s Disease: Preclinical Evaluation of Optimally Configured TH:CH1 Fusion for Maximal Dopamine Synthesis

Q2 · MEDICINE

ArticleOA

Author: Hosomi, Koichi ; Kelleher, Michelle ; Gipchtein, Pauline ; Robert, Camille ; Palfi, Stéphane ; Mitrophanous, Kyriacos A ; Stewart, Hannah ; Hantraye, Philippe ; Ralph, G Scott ; Fayard, Audrey ; Gourlay, Jeanne ; Van Camp, Nadja ; Binley, Katie ; Lad, Yatish ; Jan, Caroline ; Badin, Romina Aron ; Loader, Julie

A recent phase I-II, open-label trial of ProSavin, a lentiviral vector delivering the key enzymes in the dopamine biosynthetic pathway to non-dopaminergic striatal neurons, demonstrated safety and improved motor function in parkinsonian patients. However, the magnitude of the effect suggested that optimal levels of dopamine replacement may not have been achieved. OXB-102, a lentiviral vector with an optimized expression cassette for dopamine biosynthesis, has been shown to achieve a significantly higher dopamine yield than ProSavin. We assessed the efficacy of OXB-102 in the MPTP macaque model of Parkinson's disease (PD). At 6 months post-vector administration, all treated animals showed significant improvements in clinical scores and spontaneous locomotor activity compared to controls, with the highest recovery observed in the OXB-102 high-dose (HD) group. Positron emission tomography quantification of 6-[¹⁸F]-fluoro-L-m-tyrosine uptake showed a significant increase in amino acid decarboxylase activity for all treated animals, compared with controls, where the OXB-102 HD group showed the highest level of dopaminergic activity. A toxicology study in macaques demonstrated that the vector was safe and well tolerated, with no associated clinical or behavioral abnormalities and no immune response mounted against any transgene products. Overall, these data support the further clinical development of OXB-102 for the treatment of PD.

01 Sep 2018·Human gene therapy. Clinical developmentQ3 · MEDICINE

Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease

Q3 · MEDICINE

Article

Author: Mason, Sarah ; Hantraye, Philippe ; Palfi, Stéphane ; Gurruchaga, Jean Marc ; Tuckwell, Nicola J. ; Ralph, G. Scott ; Howard, Katy ; Lepetit, Hélène ; Buttery, Philip C. ; Mitrophanous, Kyriacos A. ; Barker, Roger A. ; Gouello, Gaëtane ; Domenech, Philippe

Parkinson's disease is typically treated with oral dopamine replacement therapies. However, long-term use is complicated by motor fluctuations from intermittent stimulation of dopamine receptors and off-target effects. ProSavin, a lentiviral vector based gene therapy that delivers local and continuous dopamine, was previously shown to be well tolerated in a Phase I/II first-in-human study, with significant improvements in motor behavior from baseline at 1 year. Here, patients with Parkinson's disease from the open-label trial were followed up in the long term to assess the safety and efficacy of ProSavin after bilateral injection into the putamen. Fifteen patients who were previously treated with ProSavin have been followed for up to 5 years, with some having been seen for 8 years. Eight patients received deep brain stimulation at different time points, and their subsequent assessments continued to assess safety. Ninety-six drug-related adverse events were reported (87 mild, 6 moderate, 3 severe) of which more than half occurred in the first year. The most common drug-related events were dyskinesias (33 events, 11 patients) and on-off phenomena (22 events, 11 patients). A significant improvement in the defined "off" Unified Parkinson's Disease Rating Scale part III motor scores, compared to baseline, was seen at 2 years (mean score 29 · 2 vs. 38 · 4, n = 14, p < 0.05) and at 4 years in 8/15 patients. ProSavin continued to be safe and well tolerated in patients with Parkinson's disease. Moderate improvements in motor behavior over baseline continued to be reported in the majority of patients who could still be evaluated up to 5 years of follow-up.

News (Medical) associated with AXO Lenti PD(Oxford Biomedica)

26 May 2021

·www.globenewswire.com

Global Gene and Cell Therapies Targeting CNS Disorders

Dublin, May 26, 2021 (GLOBE NEWSWIRE) -- The "Gene and Cell Therapies Targeting CNS Disorders - Market Insights and Market Forecast - 2026" report has been added to ResearchAndMarkets.com's offering. This 'Gene and Cell Therapies targeting CNS Disorders - Market Insights and Market Forecast - 2026' report delivers an in-depth understanding of the market trends of Gene and Cell Therapies targeting CNS Disorders in in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom), and Japan. The Gene and Cell Therapies targeting CNS Disorders market report provides current treatment practices, emerging drugs, market share of the individual therapies, current and forecasted Gene and Cell Therapies targeting CNS Disorders market size from 2018 to 2026, in the 7MM. The report also covers the current Gene and Cell Therapies targeting CNS Disorders treatment practice, market drivers, market barriers, and unmet medical needs to curate the best opportunities and assesses the underlying market potential. Gene and Cell Therapies targeting CNS Disorders emerging drugs NurOwn (BrainStorm Cell Therapeutics) is is mesenchymal stromal stem cells based therapy secreting neurotrophic factors (MSC-NTF) cells. It is designed to target disease pathways in neurodegenerative disorders by effectively delivering NTFs directly to the site of damage. MSC-NTF cells are generated using autologous, mesenchymal stem cells (MSCs) that have been extracted from bone marrow, expanded and differentiated ex-vivo. The therapy is currently under clinical evaluation in phase III for the treatment of Amyotrophic lateral sclerosis (ALS) and in phase II for treatment of Multiple Sclerosis, Chronic Progressive. Neuro-Cells (Neuroplast) is an autologous cell preparation that aims to decrease inflammation and reduce cell death. Neuro- Cells is produced in a certified and patented closed system manufacturing process from bone marrow and is a registered Advanced Therapy Medicinal Product (ATMP). Based on these mechanisms, Neuroplast focuses on developing a stem cell therapy, which can inhibit the inflammatory processes following damaged/dying neural tissue cells and sees its Neuro-Cells as a disease-modifying therapy (DMT). Currently it is being evaluated in phase I and phase II/III clinical studies in treatment of Spinal Chord Injuries (SCI). Gene and Cell Therapies targeting CNS Disorders Drugs Uptake This section focuses on the rate of uptake of the potential drugs recently launched or expected to get launched in the market during the study period 2018-2026. The analysis covers Gene and Cell Therapies targeting CNS Disorders market uptake by drugs, patient uptake by therapies, and sales of each drug. This helps in understanding the drugs with the most rapid uptake, reasons behind the maximal use of new drugs, and allow the comparison of the drugs based on market share and size, which again will be useful in investigating factors important in the market uptake and in making financial and regulatory decisions. Gene and Cell Therapies targeting CNS Disorders Pipeline Development Activities The report provides insights into different therapeutic candidates in Phase III, Phase II/III, Phase II, and Phase I/II stage. It also analyses Gene and Cell Therapies targeting CNS Disorders' key players involved in developing targeted therapeutics. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition, and merger, licensing, and patent details for Gene and Cell Therapies targeting CNS Disorders emerging therapies. Key Topics Covered: 1. Key Insights2. Report Introduction3. Executive Summary4. Gene and Cell Therapies targeting CNS disorders: Overview4.1. Introduction to CNS Disorders4.2. Role of Cell and Gene Therapy in CNS Disorders4.3. Multiple Sclerosis4.4. Parkinson's disease4.5. Spinal cord injury4.6. Amyotrophic Lateral Sclerosis4.7. Huntington's disease4.8. Alzheimer's disease4.9. Spinal Muscular Atrophy5. Landscape Assessment5.1. Regulatory Scenario of Cell and Gene Therapies in the 7MM5.2. United States5.3. The European Union5.3.1. United Kingdom5.3.2. Germany5.3.3. France5.3.4. Italy5.3.5. Spain5.4. Japan5.5. Reimbursement Scenario of Cell and Gene Therapies in the 7MM5.5.1. United States5.5.2. United Kingdom5.5.3. Germany5.5.4. France5.5.5. Italy5.5.6. Spain5.5.7. Japan5.6. Mergers and Acquisitions5.7. Industry News and Policies by Regions5.7.1. Industry News5.7.2. Policies and Government Initiatives for Cell and Gene Therapies6. Marketed Products6.1. Zolgensma: Novartis7. Emerging Therapies for Amyotrophic Lateral Sclerosis7.1. NurOwn: BrainStorm Cell Therapeutics7.2. Engensis: Helixmith7.3. HYNR-CS inj: Corestem7.4. Q Cells: Q therapeutics7.5. VM202: Helixmith7.6. RAPA-501 Autologous T cells: Rapa Therapeutics8. Emerging Therapy for Multiple sclerosis8.1. NurOwn: BrainStorm Cell Therapeutics8.1.1. Product Description8.1.2. Product Developmental Activities9. Emerging Therapy for Spinal Cord Injury9.1. Neuro-Cells: Neuroplast9.2. Umbilical Cord Blood Mononuclear Cell: StemCyte9.3. FAB117-HC: Ferrer Internacional9.4. Human spinal cord stem cells: Neuralstem9.5. FAB117-HC: Ferrer Internacional10. Emerging therapies for Alzehimer10.1. itMSCs: Stemedica Cell Technologies10.2. AAV-hTERT: Libella Gene Therapeutics10.3. ST-501: Sangamo Therapeutics11. Emerging Therapies for Parkinson Disease11.1. VY-AADC: Hoffmann-La Roche11.2. Lomecel-B: Longeveron11.3. OXB-102: Sio Gene Therapies11.4. PR001: Prevail Therapeutics (Eli Lilly and Company)11.5. Neural Stem Cell-Derived Neurons: NeuroGeneration11.6. AAV2-GDNF: Brain Neurotherapy Bio (AskBio)12. Emerging Therapy for Huntington12.1. Intra-striatal rAAV5-miHTT: UniQure Biopharma12.1.1. Product Description12.1.2. Research and Development12.1.3. Product Developmental Activities13. Company Profiles For more information about this report visit

Gene TherapyCell TherapyAcquisitionCollaborate

11 Mar 2019

·www.biospace.com

Axovant Releases Positive Interim Updates for Parkinson’s and Tay-Sachs Gene Therapy Trials

Axovant has been busy, releasing interim results from two different clinical trials, one for Tay-Sachs, the other for Parkinson’s disease. Axovant has been busy, releasing interim results from two different clinical trials, one for Tay-Sachs, the other for Parkinson’s disease. For Parkinson’s disease, Axovant released positive interim results from the first cohort of its SUNRISE-PD Phase II clinical trial of AXO-Lenti-PD. AXO-Lenti-PD is a gene therapy that delivers three genes, tyrosine hydroxylase, cyclohydrolase 1, and aromatic L-amino acid decarboxylase, by way of a single lentiviral vector. These genes code for a group of enzymes required for dopamine synthesis. The cohort involved two patients with advanced Parkinson’s disease. They both received a single administration of the lowest dose of the therapy. It was well-tolerated, and no serious adverse events were observed. At three months after receiving the therapy, improvements of an average of 55 percent from baseline were observed, based on the Unified Parkinson’s Disease Rating Scale (UPDRS) Total OFF score. “Our focus in this first cohort of the SUNRISE-PD study was on the safety and tolerability of AXO-Lenti-PD, as well as the evaluation of efficacy using well-validated, objective measures,” stated Gavin Corcoran, Axovant’s executive vice president of Research and Development. “These early data support the safety of the lowest dose of AXO-Lenti-PD, similar to what was observed with the earlier generation construct, ProSavin, and also suggest substantially greater biological activity than the highest dose of ProSavin previously tested. These findings are highly encouraging, and we look forward to advancing to higher dose cohorts where we will explore the full clinical potential of AXO-Lenti-PD in patients with Parkinson’s disease.” The bottom line appears to be that AXO-Lenti-PD is safe at the lower dosage and appears at least as effective as an early version, ProSavin, significantly improving motor function in patients with advanced Parkinson’s disease. Axovant also announced a clinical update on its first patient dosed with AXO-AAV-GM2 gene therapy for advanced infantile Tay-Sachs disease. AXO-AAV-GM2 is a gene therapy for GM2 gangliosidosis, also known as Tay-Sachs and Sandhoff diseases. They are a group of rare and fatal pediatric neurodegenerative diseases caused by mutations in the HEXA gene, which causes Tay-Sachs, and the HEXB gene, which causes Sandhoff disease. These genes code for two subunits of the ß-hexosaminidase A (Hex A) enzyme. The announcement described three-month data from the trial evaluating dose of the therapy in a 30-month-old child with advanced infantile Tay-Sachs. It was administered into the cisterna magna and lumbar spinal canal only. Because of the patient’s advanced disease, the intrathalamic injection wasn’t administered. The company indicates that future patients, who are expected to be treated earlier in the disease, will also receive the therapy into the thalamus bilaterally in addition to into the cisterna magna and spinal canal. The therapy was generally well-tolerated. No serious adverse events were reported as of the three-month visit. The patient’s clinical condition was stable from baseline to the third month without any neurological clinical deterioration observed in either the neurological exam or the MRI. There was also an increase of ß-Hexosaminidase A to 1.44 percent of normal. “Our first priority has been to identify a vector construct and route of delivery that can reconstitute a clinically important level of enzyme activity in a safe manner,” stated Terence R. Flotte, professor of pediatrics and dean of the School of Medicine at the University of Massachusetts Medical School. Flotte is the principal investigator of the trial. “This first demonstration of the feasibility of human gene therapy for Tay-Sachs disease is a tribute to the tremendous collaborative effort between the research teams at UMass Medical School and Auburn University, and provides a strong foundation for the transition of this program to the team at Axovant.”

Clinical ResultGene TherapyPhase 2

10 Dec 2018

·www.biospace.com

Axovant Abandons Another Dementia Drug After Failed Trial

There is very little doubt that developing drugs for neuroscience disorders in general and dementias in particular is a high-risk business. Axovant Sciences, unfortunately, seems to be finding that out the hard way. There is very little doubt that developing drugs for neuroscience disorders in general and dementias in particular is a high-risk business. Axovant Sciences , unfortunately, seems to be finding that out the hard way. The company announced today that its Phase II clinical trial of nelotanserin for the treatment of REM sleep behavior disorder (RBD) in patients with Lewy body dementia (LBD) failed to meet its primary efficacy endpoint. The endpoint was reduction in frequency of RBD events as measured by sleep laboratory video. “While secondary measures of efficacy suggest biologic activity for nelotanserin, Axovant has been focused on developing innovative gene therapies and we will not undertake further clinical studies with our legacy small molecule portfolio, including nelotanserin,” stated Pavan Cheruvu , Axovant’s chief executive officer. “The completion of this study closes a chapter in the company’s history. We are grateful to the patients and clinical investigators who participated in this study, and we look forward to advancing Axovant’s gene therapy pipeline through multiple important milestones in 2019.” Axovant is under Vivek Ramaswam y’s Roivant Sciences ’ umbrella. Broadly speaking, Ramaswamy’s business model is to acquire cast-off drugs from larger pharma companies to develop them in smaller, more focused or “other” indications. At least in Axovant’s case, this isn’t working well. Most notoriously—and one suspects Axovant and Ramaswamy wish the media would stop bringing it up—Axovant’s first drug, intepirdine, failed a Phase III MINDSET clinical trial in Alzheimer’s disease in September 2017. Ramaswamy and Axovant bought the drug for $5 million from GlaxoSmithKline . It showed a favorable safety and tolerability profile, and even demonstrated immediate and sustained efficacy over placebo in a Phase IIb trial. But GSK had run four clinical trials, all failures, and abandoned the drug. Axovant studied the drug in 1,315 patients on a stable background therapy of donepezil (Aricept) and received either intepirdine or a placebo. But the drug failed to meet its co-primary efficacy endpoints. The company stated at the time, there was “essentially no difference between the intepirdine and placebo arms in change from baseline in activities of daily living.” The company then spent the next six months reorganizing . In May 2018, it announced these changes. David Hung , the founder, president and chief executive officer of Medivation , had taken over Axovant in April 2017 after Pfizer acquired Medivation in September 2016. He stuck around until the intepirdine failure, then left. Gavin Corcoran joined Axovant as executive vice president of Research & Development, and Michael Hayden was appointed senior scientific advisor and chairman of the Scientific Advisory Board. Cheruvu came on as chief executive in February. The Axovant restructuring was also part of an overall Roivant restructuring, where more of the companies under the Roivant umbrella shared resources. In June, 2018, Axovant licensed OXB-102, now called AXO-Lenti-PD, from Oxford BioMedica . The drug is an investigational gene therapy for Parkinson’s disease, designed to deliver three genes that encode a set of enzymes required for dopamine synthesis in the brain. The company indicates that since it licensed OXB-102, it has been focused on gene therapies. It is currently in the SUNRISE-PD Phase II clinical trial with data expected in March 2019. Axovant is also developing AXO-AAV-OPMD, a gene therapy using Silence-and-Replace technology to restore normal muscle function in patients with oculopharyngeal muscular dystrophy (OPMD). It expects to launch a clinical trial for that therapy in the second half of 2019. Meanwhile, today’s news was met with a 27 percent drop in stock.

Phase 2Gene TherapyAcquisitionExecutive ChangePhase 3

100 Deals associated with AXO Lenti PD(Oxford Biomedica)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 2	France	Oxford Biomedica Plc	01 Jan 2008
Parkinson Disease	Phase 2	United Kingdom	Oxford Biomedica Plc	01 Jan 2008

Clinical Result

Indication

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03720418 (SUNRISE-PD, MDS2021)	Phase 1/2	Parkinson Disease	4	ALPD low dose (4.2E+6 TU)	evksguyvzk(djhcesfopj) = One subject had two serious adverse events of confusional state and wound infection which resolved and were unrelated to ALPD and possibly related to the surgical procedure firiueqoib (nbhmvktqom ) View more	-	17 Sep 2021
				ALPD mid dose (1.4E+7 TU)
NCT03720418 (GlobeNewswire) Manual	Phase 2	Parkinson Disease	4	AXO-Lenti-PD Gene Therapy	kbkboftlnq(cnvegfdyqk) = lwddchbivr zyvczmnrng (jszfjoqywe ) View more	Positive	06 Oct 2020
OXB-102 (ASGCT2014)	Not Applicable	Parkinson Disease tyrosine hydroxylase \| aromatic L-amino acid decarboxylase \| GTP-cyclohydrolase	-	OXB-102 full-strength dose	cubikwfjrg(acusnbdaoi) = muscmwgjhb tnxisnmimx (ohovhpfsjj ) View more	Positive	01 May 2014
				OXB-102 1/5th dose	cubikwfjrg(acusnbdaoi) = gjniuwwshf tnxisnmimx (ohovhpfsjj ) View more
ProSavin (ESGCT2010)	Phase 1	Parkinson Disease	-	ProSavin	irfunyourp(xiidssovcc) = quuhwizusa thjickykna (vexfdcucqr )	Positive	22 Oct 2010

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AXO Lenti PD(Oxford Biomedica)

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