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Clinical Trials

Date: 2018-05-18

Type of information: Presentation of results at a congress

phase: 1-2

Announcement: presentation of results the 21st Annual Meeting of the ASGCT (American Society for Gene and Cell Therapy)

Company: Abeona Therapeutics (USA - NY)

Product: ABO-102 (SC AAV-SGSH)

Action mechanism:

  • gene therapy. ABO-102 (AAV SGSH) is a next generation adeno-associated viral (AAV)-based gene therapy for MPS IIIB. This gene therapy involve a one-time delivery of a genetically modified virus to deliver a normal copy of the defective gene to cells of the central nervous system and peripheral organs with the aim of reversing the effects of the genetic errors that cause the disease. After a single dose in preclinical animal models of Sanfilippo syndrome ABO-102 induced cells in the CNS and peripheral organs to produce the missing enzymes and help repair damage caused to the cells. Preclinical in-vivo efficacy studies in animals with Sanfilippo syndrome have demonstrated functional benefits that remain for months after treatment. A single dose significantly restored normal cell and organ function, corrected cognitive defects that remained months after drug administration, increased neuromuscular control and increased the lifespan of animals with MPS III over 100% one year after treatment compared to untreated control animals.
  • ABO-102 has been granted Regenerative Medicine Advanced Therapy, Rare Pediatric Disease, and Fast Track designations in the United States, and Orphan Product Designation in both the United States and the European Union.

Disease: mucopolysaccharidosis type IIIA (Sanfilippo B syndrome)

Therapeutic area: Rare diseases - Genetic diseases

Country: USA

Trial details:

  • The ongoing Phase 1/2 clinical trial, which has received FastTrack designation, Orphan Product Designation, and Rare Pediatric Disease designation by the FDA, is designed to evaluate safety and efficacy of ABO-102 in patients with MPS IIIA. Per the design of the trial, subjects receive a single, intravenous injection of ABO-102 to deliver the AAV viral vector systematically throughout the body to introduce a corrective copy of the gene that underlies the cause of the MPS IIIA disease, particularly the CNS. Subjects are evaluated at multiple time points over the initial six-months post-injection for safety assessments and initial signals of biopotency. The global clinical study is supported by a 25-subject MPS III Natural History Study, which included potential efficacy assessments consisting of neurocognitive evaluations, biochemical assays and MRI data generated over one year of follow-up assessments. (NCT02716246)

Latest news:

  • • On May 18, 2018, Abeona Therapeutics announced updated clinical data from the Phase 1/2 trial for ABO-102 (AAV-SGSH), the company’s clinical gene therapy for the treatment of Sanfilippo syndrome type A (MPS III A) during the 21st Annual Meeting of the ASGCT (American Society for Gene and Cell Therapy) in Chicago, IL. The ongoing ABO-102 (AAV-SGSH) trial results demonstrate robust and durable clinical effects achieved throughout various timepoints post-administration. To date, 11 patients have been dosed with a single intravenous injection of ABO-102. Each subject received a single intravenous injection of the gene therapy for systemic delivery of a functional copy of the missing SGSH gene associated with onset and progression of the disease. Select updated data from the presentation are highlighted below: Biopotency Assessments: ABO-102 continues to demonstrate significant dose-dependent and time-dependent responses in key biomarkers through 18-months post-injection, including sustained reductions of heparan sulfate, the sugar molecule that is the hallmark of MPS IIIA, in the cerebral spinal fluid (CSF) and urine. CSF heparan sulfate: Day 360 assessment Cohort 1 (n=2) demonstrated a reduction of 69.3% Cohort 2 (n=2) demonstrated a reduction of 65.7% Day 180 assessment Cohort 1 (n=3) demonstrated a reduction of 58.7% Cohort 2 (n=3) demonstrated a reduction of 60.5% Cohort 3 (n=1) demonstrated a reduction of 83.3% Day 30 assessment Cohort 1 (n=3) demonstrated a reduction of 25.8% Cohort 2 (n=3) demonstrated a reduction of 52.1% Cohort 3 (n=4) demonstrated a reduction of 67.1% Urine heparan sulfate: Day 540 assessment Cohort 1 (n=3) demonstrated a reduction of 30.0% Day 360 assessment Cohort 1 (n=3) demonstrated a reduction of 29.2% Cohort 2 (n=2) demonstrated a reduction of 45.1% Day 180 assessment Cohort 1 (n=3) demonstrated a reduction of 29.2% Cohort 2 (n=2) demonstrated a reduction of 57.6% Cohort 3 (n=1) demonstrated a reduction of 75.0% Day 90 assessment Cohort 1 (n=3) demonstrated a reduction of 54.2% Cohort 2 (n=3) demonstrated a reduction of 63.1% Cohort 3 (n=4) demonstrated a reduction of 77.1% Day 30 assessment Cohort 1 (n=3) demonstrated a reduction of 64.2% Cohort 2 (n=3) demonstrated a reduction of 54.0% Cohort 3 (n=3) demonstrated a reduction of 90.3% Biophysical Assessments: A supportive natural history study (Truxal et. al., 2016, Mol. Genet. Metab.) in MPS IIIA demonstrated that subjects showed, on average, 2.2 times increased liver volumes over normal. Results from the Phase 1/2 clinical trial for ABO-102 demonstrate durable biophysical reductions of disease burden including reductions in liver volume. Safety Assessments: ABO-102 is well-tolerated in all subjects to date, with no drug-related serious adverse events (SAE) reported through over 4,200 cumulative days post-injection. • On February 8, 2018, Abeona Therapeutics announced updated clinical data from the ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH), the company’s investigational gene therapy for the treatment of Sanfilippo syndrome Type A (MPS IIIA). The results demonstrate robust and durable clinical effects achieved throughout various timepoints post-administration. To date, 10 patients have been dosed with a single intravenous injection of ABO-102. Results were reported during the WORLDSymposium for Lysosomal Diseases. In the trial, subjects received a single intravenous injection of ABO-102 to facilitate systemic delivery of a corrective copy of the gene associated with onset and progression of MPS IIIA. Subjects were evaluated at multiple time points post-injection for safety assessments and signals of biopotency and clinical activity.
  • Select updated data from the presentation are highlighted below:
  • Biopotency Assessments: ABO-102 continues to demonstrate significant dose-dependent and time-dependent responses in measured biomarkers, including rapid and sustained reductions of heparan sulfate (HS), the sugar molecule that is the hallmark of MPS IIIA, in the cerebral spinal fluid (CSF) and urine.CSF heparan sulfate: Day 180 assessment Cohort 2 (n=3) demonstrated a reduction of 57.1% +/- 7.14%
  • Day 30 assessment Cohort 3 (n=3) demonstrated a reduction of 64.4% +/- 2.2% Urine heparan sulfate (HS):
  • Day 30 assessment Cohort 3 (n=3) demonstrated a reduction of 91.9% +/-1.5% Cohort 2 (n=3) demonstrated a reduction of 54.0% +/- 18.0%
  • Day 60 assessment Cohort 3 (n=4) demonstrated a reduction of 73.4% +/- 13.5% Cohort 2 (n=3) demonstrated a reduction of 65.2% +/- 5.5%
  • Day 90 assessment Cohort 3 (n=1) demonstrated a reduction of 94.9 % Cohort 2 (n=3) demonstrated a reduction of 63.1%+/- 8.2%
  • Day 180 assessment Cohort 2 (n=2) demonstrated a reduction of 55.0% +/- 5.0% Cohort 1 (n=2) demonstrated a reduction of 29.2% +/- 35.6%
  • Biophysical Assessments: A separate natural history study (Truxal et. al., 2016, Mol. Genet. Metab.) of MPS IIIA demonstrated that subjects showed an average 220% increase in liver volume at baseline. Result from the Phase 1/2 clinical trial for ABO-102 demonstrate durable biophysical reductions of disease burden including reductions in liver volume.Cognitive Assessments: ABO-102 continues to show evidence of stabilization or improvement in cognitive function at six months in Cohort 2 and one year in Cohort 1.Two of the three treated patients from Cohort 2 showed evidence of improvement in the Leiter-R non-verbal IQ and stabilized Vineland (adaptive behavior) scales. Safety Assessments: ABO-102 is well-tolerated in all subjects to date, with no drug-related serious adverse events (SAE) reported through over 3,100 cumulative days post-injection.
  • • On May 12, 2017, Abeona Therapeutics announced updated data from the ongoing gene therapy clinical trial for Sanfilippo syndrome Type A (MPS IIIA) at the American Society Gene and Cell Therapy (ASGCT) 20th Annual Meeting. “Abeona continues to advance gene therapy for MPS IIIA patients and we are excited about the positive dose response in the CNS seen in Cohort 2. The observation of a dose response supports our clinical approach, and we are encouraged to observe further reductions in central nervous system (CNS) heparan sulfate, reduction in liver volume, and preliminary evidence of slowed neurocognitive decline, are very encouraging. We look forward to accelerating enrollment with the recently initiated global sites (Spain and Australia) and reporting additional clinical data in the ABO-102 global MPS IIIA trial later this year,” stated Timothy J. Miller, Ph.D., President and CEO of Abeona Therapeutics.
  • Highlights reported data on five (n=3 Cohort 1, n=2 Cohort 2) out of the six patients treated to date in the gene therapy trial included:
  • Biopotency: positive dose response observed in Cohort 2.
  • --At 30 days post-injection, two patients in the Cohort 2 demonstrated 60.7%(+/- 8.8%) reduction in cerebral spinal fluid (CSF) heparan sulfate (HS).
  • Hepatosplenomegaly: consistent reduction in liver volume observed.
  • --At 30 days post-injection, Cohort 2 subjects demonstrated reductions in liver volumes of 14.81% (+/- 1.2%).
  • --The natural history study in 25 subjects with MPS III (Truxal et. al., 2016, Mol. Genet. Metab.) demonstrated that subjects had increased liver volumes averaging 116% at baseline that did not change over a year of follow-up.
  • Cognitive Assessments: evidence of cognitive stabilization at six months in Cohort 1.
  • --Cognitive assessments, taken at baseline, at the six-month timepoint for the Cohort 1 (n=3), subjects showed evidence of stabilization or improvement in the Leiter-R non-verbal IQ and Vineland (adaptive behavior) scales.
  • --Cognitive assessments are taken at six-month and twelve-month follow-up visits.
  • --Leiter Nonverbal IQ assessments in Cohort 1 subjects demonstrated stabilized or improved scores at six-months post-injection. Notably, one subject improved +10 (+/-6) points, while age-matched controls in the Natural History study would have predicted a decrease of -11.1 (+/-2.7) points over 6 months.
  • --Vineland assessments in Cohort 1 at six months post-injection suggest stabilization in adaptive behavior scores.
  • Safety: well-tolerated in all subjects through 1100 days cumulative post-injection.
  • --No serious adverse events (SAEs) reported in subjects in either cohort receiving ABO-102 (Cohort 1: 5E12 vg/kg and Cohort 2: 1E13 vg/kg).
  • • On May 9, 2017, Abeona Therapeutics announced Australian regulatory approval to initiate a Phase 1/2 for the ABO-102 gene therapy program for patients with Sanfilippo syndrome type A (MPS IIIA). The clinical study was approved by the Australian Government Department of Health Therapeutic Goods Administration and the Company is conducting the Phase 1/2 clinical study at Adelaide Women’s and Children’s Hospital, Australia.
  • • On February 17, 2017, Abeona Therapeutics announced updated data from the ongoing gene therapy clinical trial for Sanfilippo syndrome Type A (MPS IIIA), at the 13th Annual WORLDSymposium™ 2017 lysosomal storage disorders conference.  Per the design of the clinical trial, subjects received a single, intravenous injection of ABO-102 to deliver the AAV viral vector systematically throughout the body to introduce a corrective copy of the gene that underlies the cause of the MPS IIIA disease. Subjects are evaluated at multiple time points post-injection for safety assessments and initial signals of biopotency and clinical activity, which suggest that ABO-102 successfully reached target tissues throughout the body, including the central nervous system. Observations reported at the WORLDSymposium™ conference included:
  • Safety: ABO-102 is well-tolerated in subjects injected with the low dose of 5E13 vg/kg ABO-102, with no treatment related adverse events or serious adverse events (SAEs) through over 650 days cumulative post-injection. Enrollment in the high dose cohort has commenced with no Serious Adverse Events (SAEs) reported to date.
  • Biopotency: As reflected in published natural history studies evaluating MPS III subjects, cerebral spinal fluid (CSF) and urine GAG (heparan sulfate or “HS”) are significantly elevated in the subject population as a symptom of disease pathology. As announced previously, all subjects in the low-dose cohort experienced reductions from baseline in CSF HS of 25.6% +/- 0.8%, suggesting ABO-102 crossed the blood brain barrier after intravenous administration. At the six-month follow-up (n=2), CSF HS continued to decrease to 63.1% +/- 0.5% of baseline values, suggesting further improvement in the elimination of the storage pathology. Data presented showed reduction in urinary heparan sulfate and urinary total GAG fragments. Hepatosplenomegaly: The natural history study in 25 subjects with MPS III (Truxal et. al., 2016, Mol. Genet. Metab.) demonstrated that subjects had increased liver and spleen volumes averaging 116% and 88%, respectively at baseline that did not change over a year of follow-up. All three subjects demonstrated significant reductions in liver volumes at 30-days post injection (17.1% +/- 1.9%). At the six-month follow-up in low dose subjects (n=2), this effect was sustained, with a liver volume further decreased by 29.7 – 30.3% and spleen volume by 2.2 – 12.9% from baseline. Cognitive Assessments: The clinical trial utilizes three validated neurocognitive and behavioral assessment tools, including the Leiter International Performance Scale Third Edition (Leiter-3), the Vineland Adaptive Behavior Scale, Second Edition (Vineland-II) and the Mullen Scale of Early Learning. Cognitive assessments are taken at baseline, and have been taken at the six-month (n=2) and will be taken at the twelve-month follow-up visits. These assessments provide the opportunity to measure several sub-domains, such as fine motor, visual acuity, expressive language, receptive language, among others. Assessments at six-month for the first two lose-dose patients provided early evidence of cognitive stabilization. The two subjects assessed at the 6-month timepoint showed evidence for stabilization or improvement of scores (average of 60% across 2 subjects) in several Mullen subdomains. Adaptive behavior ratings on the Vineland also stabilized. Both subjects showed improved ability to complete individual items on the Leiter-R non-verbal IQ assessment resulting in improved raw scores.
  • •  On February 1, 2017, Abeona Therapeutics announced that the first high-dose subject was enrolled in the ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH). Previously announced 30-day post-injection data for the low dose cohort indicated:
  • ABO-102 reduced GAG (heparan sulfate) in urine 57.6% +/- 8.2% ABO-102 reduced GAG (heparan sulfate) in the CSF 25.6% +/- 0.8% Reduction in liver volume of 17.7% +/- 1.9% Reduction in spleen volume of 17.6% +/- 7.1%
  • •  On October 20, 2016, Abeona Therapeutics provided at the Orphan Drugs & Rare Disease Conference (London, UK), an update on clinical results through 30 days post-injection for the completed low-dose cohort (n=3) in the ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH). Observations 30 days post-injection for the low dose cohort demonstrated: ABO-102 is well-tolerated in subjects injected with the low dose of 5E13 vp/kg ABO-102 with no treatment related adverse events or serious adverse events (SAEs). Following favorable review of the safety data by the independent Data Safety Monitoring Board (DSMB), enrollment in the high dose cohort has commenced. In the natural history study evaluating MPS III subjects it was shown that urine and cerebral spinal fluid GAG (heparan sulfate or "HS") are significantly elevated in the subject population as a symptom of disease pathology. All subjects in the low-dose cohort experienced reductions from baseline in both urinary HS and CSF. At 30 days post-injection, urinary HS reduction was 57.6% +/- 8.2%. Reduction in CSF HS was 25.6% +/- 0.8%, suggesting that ABO-102 crossed the blood brain barrier after intravenous administration. All three subjects demonstrated significant reductions in liver volume (17.1% +/- 1.9%), and spleen volume (17.6% +/- 7.1%) from baseline, as measured by MRI at 30 days post-injection. Per the design of the clinical trial, subjects in the low-dose cohort received a single, intravenous injection of AB0-102 to deliver the AAV viral vector systematically throughout the body to introduce a corrective copy of the gene that underlies the cause of the MPS IIIA disease. Subjects were evaluated at multiple time points over the initial 30 days post-injection for safety assessments and initial signals of biopotency, which suggest that ABO-102 successfully reached target tissues throughout the body, including the central nervous system, to reduce GAG content that underlies the lysosomal storage pathology central to Sanfilippo syndrome type A (MPSIIIA). A more complete analysis of these data will be presented from the low-dose cohort and initial high dose cohort at a scientific conference in the first quarter of 2017. The Data Safety Monitoring Board has approved dose escalation of the high dose cohort this quarter.
  • •  On August 29, 2016, Abeona Therapeutics announced that enrollment has been completed for the low-dose cohort (n=3) in its ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH). The company recently announced that ABO-102 is well tolerated in initial subjects and preliminary biopotency appears promising.
  • • On August 4, 2016,  Abeona Therapeutics announced European regulatory approval for a Phase 1/2 Gene Therapy Clinical Trial utilizing ABO-102 (AAV-SGSH) for patients with Sanfilippo syndrome type A (MPS IIIA). The clinical study was approved by the Agencia Espanola de Medicamentos y Productos Sanitarios, and the Company is conducting the Phase 1/2 clinical study at Cruces University Hospital (Bilbao, Spain).
  • •  On August 2, 2016, Abeona Therapeutics provided an update on its ongoing Phase 1/2 trial for ABO-102 (AAV-SGSH), enrolling at Nationwide Children's Hospital (Columbus, Ohio). Following a review of safety data by independent Data Safety and Monitoring Board (DSMB) on the initial patient enrolled, a second patient has been enrolled and treated. Additionally, preliminary measures of clinically relevant biomarkers provide promising signals of potential systemic and CNS clinical benefits for patients suffering with MPS IIIA.
  • •  On May 17, 2016, Abeona Therapeutics announced that the first patient in a Phase 1/2 trial for ABO-102 (AAV-SGSH), a single treatment gene therapy strategy for patients with Sanfilippo syndrome type A has been enrolled at Nationwide Children's Hospital (Columbus, Ohio). The clinical study is supported by neurocognitive testing data generated in a 25-subject MPS III Natural History Study, where all patients are through 1 year of follow up assessments.
  • •  On February 29, 2016, Abeona Therapeutics announced the FDA cleared the Company's Investigational New Drug Application for ABO-102 (AAV- SGSH) for mucopolysaccharidosis type IIIA (MPS IIIA). The ABO-102 IND application is now active and enables Nationwide Children's Hospital (Columbus, OH) to initiate a Phase 1/2 clinical study designed to assess the safety, tolerability and potential efficacy of ABO-102 in children with MPS IIII A.
  • • On January 11, 2016, Abeona Therapeutics announced the Interministerial Council of Genetically Modified Organisms has approved the Genetically Modified Organism (GMO) Voluntary Release regulatory filings for Phase 1/2 gene therapy clinical study to treat patients with  ABO-102 (AAV SGSH) for patients with Sanfilippo syndrome type A (MPS IIIA). Additionally, the Comite Etico De Investigacion Clinica de Euskadi (CEIC-E) has approved the ethical committee regulatory filings for ABO-102. The company plans to file CTAs for the program shortly for the upcoming clinical studies to be conducted at Cruces University Hospital (Bilbao, Spain).
 

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