• Interview with Dwight Koeberl, MD, PhD at Duke University
• Early results from Actus-101 phase 1/2 study (AAV2/8-LSPhGAA in Late-Onset Pompe Disease)
• First three people enrolled
• Have participated in 24 weeks of the study
• Results from low-dose branch
• No serious adverse events
• All three patients met efficacy goals and have now stopped ERT infusions entirely
• Clinical Trial Website
  • https://clinicaltrials.gov/ct2/show/NCT03533673
• Asklepios BioPharmaceutical
  • http://www.askbio.com

My Take:

This is really great news. The results are very preliminary, but the fact that all three study participants were able to quit ERT infusions at 24 weeks is potentially life-changing for thousands of people with Pompe. At this point in the study, it’s really the best news we could hope for at this early time.

There’s nothing negative about this interview, but there is certainly a lot riding on this trial. Many Pompe Disease patients are hopeful it will offer a “cure” for Pompe and possibly even reduce some symptoms that Myozyme/Lumizyme are typically not able to improve significantly (brain symptoms, for example).

Although many hope this will be something of a “silver bullet”. There are other gene therapy trials in the Pompe Disease treatment pipeline. Audentes Therapeutics in late July 2020 began recruiting patients for their gene therapy trial known as FORTIS.

Video via checkrare.com:

Five patients were cross‐reactive immunologic material (CRIM)‐negative, two in the 20 mg, three in the 40 mg group. We compared (ventilator‐free) survival, motor outcome, infusion associated reactions (IARs), and antibody formation. From 2012 on patients >2 months in the 40 mg group also received immunomodulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) in an enzyme replacement therapy (ERT)‐naïve setting.

Survival was 66% in the 20 mg group and 92% in the 40 mg group. Ventilator‐free survival was 50% and 92%. Both CRIM‐negative patients in the 20 mg group died, whereas all three are alive in the 40 mg group. In the 20 mg group, 67% learned to walk compared with 92% in the 40 mg group. At the age of 3 years, 33% and 92% were able to walk.

Peak antibody titers ranged from 1:1250 to 1:31 250 in the 20 mg group and from 1:250 to 1:800 000 in the 40 mg group. Five patients of the 40 mg group of whom two CRIM‐negative also received immunomodulation. B‐cell recovery was observed between 5.7 and 7.9 months after the last dose of rituximab. After B‐cell recovery titers of patients with and without immunomodulation were similar (ranges 1:6 250‐1:800 000 and 1:250‐1:781 250). This study shows that classic infantile patients treated with 40 mg/kg/week from the start to end have a better (ventilator‐free) survival and motor outcome. Immunomodulation did not prevent antibody formation in our study.

Esther PoelmanJan J. A. van den DorpelMarianne Hoogeveen‐WesterveldJohanna M. P. van den HoutLianne J. van der GiessenNadine A. M. E. van der BeekW. W. M. Pim PijnappelAns T. van der Ploeg

First published: 07 June 2020

https://doi.org/10.1002/jimd.12268