AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort

Al-Zaidy, Samiah; Kolb, Stephen J.; Lowes, Linda; Alfano, Lindsay; Shell, Richard; Church, Kathleen; Nagendran, Sukumar; Sproule, Douglas M.; Feltner, Douglas E.; Wells, Courtney; Ogrinc, Francis G.; Menier, M.; L’Italien, James; Arnold, W. David; Kissel, John T.; Kaspar, Brian K.; Mendell, Jerry R.

doi:10.3233/jnd-190403

Cited by 138 publications

(147 citation statements)

References 22 publications

(49 reference statements)

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“…However, for sure, for the production of other viral vectors, such as AAV, larger bioreactors are needed, as the required viral vector numbers per patient are often higher compared to lentiviral vectors. 8,37,38 Adenoviral vector production in iCELLis Nano and scale-X bioreactors…”

Section: Lentiviral Vector Yields In Icellis Nano and Scale-x Bioreacmentioning

confidence: 99%

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

et al. 2020

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We have previously produced viral vectors (lentiviral vector, adenoviral vector, and adeno-associated viral vector) in small and in commercial scale in adherent cells using Pall fixed-bed iCELLis Ò bioreactor. Recently, a company called Univercells has launched a new fixed-bed bioreactor with the same cell growth surface matrix material, but with different fixed-bed structure than is used in iCELLis bioreactor. We sought to compare the new scale-XÔ hydro bioreactor (2.4 m 2) and iCELLis Nano system (2.67 m 2) to see if the difference has any effect on cell growth or lentiviral vector and adenoviral vector productivity. Runs were performed using parameters optimized for viral vector production in iCELLis Nano bioreactor. Cell growth was monitored by counting nuclei, as well as by following glucose consumption and lactate production. In both bioreactor systems, cells grew well, and the cell distribution was found quite homogeneous in scale-X bioreactor. Univercells scale-X bioreactor was proven to be at least equally efficient or even improved in both lentiviral vector and adenoviral vector production. Based on the results, the same protocol and parameters used in viral vector production in iCELLis bioreactor can also be successfully used for the production in scale-X bioreactor system.

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Section: Lentiviral Vector Yields In Icellis Nano and Scale-x Bioreacmentioning

confidence: 99%

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

et al. 2020

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“…15 However, correlation was based on two infants who had very high baseline function at 1 month of age, who are not representative of the population of postsymptomatically identified patients. 16,17 SMN2 copy number was not significantly correlated with attainment of the sitting position. Although three copies of SMN2 are not associated with a better prognosis in patients with symptomatic SMA1 treated with nusinersen, 6,8,9 preliminary results from a study of infants treated presymptomatically with nusinersen indicated that patients with three SMN2 copies have better improvement than patients with two copies.…”

Section: Discussionmentioning

confidence: 74%

“…In the clinical trial of the gene therapy onasemnogene abeparvovec, the baseline CHOP‐INTEND score in conjunction with age was demonstrated to be a strong predictive factor of walking acquisition . However, correlation was based on two infants who had very high baseline function at 1 month of age, who are not representative of the population of postsymptomatically identified patients …”

Section: Discussionmentioning

confidence: 93%

Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Aragon-Gawinska

Daron

Ulinici

et al. 2019

Develop Med Child Neuro

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Aim To determine factors associated with acquisition of a sitting position in patients with spinal muscular atrophy type 1 (SMA1) treated with nusinersen. Method Using data from the registry of patients with SMA1 treated with nusinersen, we compared the subgroups of sitters and non‐sitters after 14 months of therapy as a function of baseline level, SMN2 copy number, age at treatment initiation, and improvement at 2 and 6 months post‐treatment initiation. We used Hammersmith Infant Neurological Examination, Section 2 (HINE‐2) and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders for motor evaluation. Results Fifty children (22 females, 28 males), mean age 22 months (SD 20.7; range 2.5–102.8mo) were treated. Data on sitting position acquisition were collected for 47 patients at month 14. Fifteen patients were able to sit unassisted; 11 of 15 had a baseline HINE‐2 score of at least 2 points and 11 of 14 had an improvement over baseline of at least 2 points at month 6. Patients who improved by 2 or more points at month 6 were three times more likely to be sitters at month 14 than those who did not. Interpretation High baseline motor function and improvement in HINE‐2 score after 6 months of treatment are associated with the probability of acquiring a sitting position in patients with SMA1 treated with nusinersen. What this paper adds Fifteen of 47 patients with spinal muscular atrophy could sit unaided 14 months after treatment with nusinersen. The number of SMN2 copies were not predictive of acquisition of a sitting position. Baseline condition and clinical response after 6 months of treatment were most predictive of sitting position acquisition.

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“…Furthermore, because muscle cells are non-dividing and long-lived, there is potential that a one-time treatment could have long-term and perhaps even life-long benefits. In fact, preclinical and clinical studies in neuromuscular diseases to date indicate no loss in durability [25,[52][53][54][55]. The objective of gene therapy for DMD is to deliver a gene encoding a functional version of dystrophin systemically to all target tissues involved in DMD pathology and thereby ameliorate the progression of the disease.…”

Section: Special Considerations For Dmd Gene Therapymentioning

confidence: 99%

“…Clinical research on gene transfer therapy has demonstrated positive outcomes including improvements in muscle function, developmental milestones, and survival in spinal muscular atrophy [22]; restoration of vision in patients who were blind; eradication of blood cancers for patients not responding to other treatments; correction of hemoglobinopathies and coagulation factor deficiencies; and immune system restoration in children born with primary immune deficiency [19,23,24]. Notably, many clinical studies report successful results with gene therapy agents in pediatric patients [25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Clinical development on the frontier: gene therapy for duchenne muscular dystrophy

Asher

Thapa

Dharia

et al. 2020

Expert Opinion on Biological Therapy

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AVXS-101 (Onasemnogene Abeparvovec) for SMA1: Comparative Study with a Prospective Natural History Cohort

Cited by 138 publications

References 22 publications

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

Sitting in patients with spinal muscular atrophy type 1 treated with nusinersen

Clinical development on the frontier: gene therapy for duchenne muscular dystrophy

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