AskBio Evaluates ACTUS-101 Gene Therapy for Late-Onset Pompe Disease


The more recent data were presented at the 2022 ASGCT Meeting.

ACTUS-101 is an adeno-associated virus (AAV) gene therapy that aims to address the deficiency of acid-alpha-glucosidase (GAA) in patients with Pompe disease. GAA deficiency leads to deleterious progressive accumulation of glycogen in organs and tissues, especially skeletal and cardiac muscle, leading to high morbidity and premature death. The current standard of care for patients with Pompe is enzyme replacement therapy (ERT).

Asklepios BioPharmaceuticalsis evaluating ACTUS-101 (AAV2/ 8-LSPhGAA) in patients with late-onset Pompe disease (LOPD) in a phase 1/2 clinical trial (NCT03533673).1The company announced that it had dosed the first patient in January 2019, although updates have been few and far in between since then. The trial is currently marked as active and not recruiting on

“This is an exciting milestone for our company but most importantly, if ACTUS-101 is successful, it could have a meaningful impact on the quality of life for those who suffer from Pompe Disease. Further, ACTUS 101 could replace enzyme replacement therapy (ERT) every other week with the potential to be a groundbreaking metabolic treatment for an unforgiving disease now showing up in an increasing number of patients” Sheila Mikhail, JD, Chief Executive Officer and Co-Founder at the time, AskBio, said in a statement about the milestone.2

The most recent data from the trial were presented at American Society of Gene & Cell Therapy 25th Annual Meeting (ASGCT) in May 2022, by Edward C. Smith, MD, pediatric neurologist and professor of pediatrics at Duke University School of Medicine.3

Investigators found that 2 weeks after treatment with AAV8-LSPhGAA, all participants demonstrated sustained serum GAA levels from 101% to 235% of baseline trough activity. All participants met criteria for ERT withdrawal at week 24 and continued to meet criteria to remain off ERT at weeks 52 and 104, although 1 participant chose to resume ERT at week 97.3

“Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for ERT by creating a liver depot for acid-GAA production,” Smith and colleagues wrote.3

The clinical trial is assessing the safety, bioactivity, and immune responses following treatment with a single infusion of ACTUS-101. The study is primarily measuring the incidence of patient reported treatment emergent adverse events (TEAEs), serious AEs, and the number of participants with abnormal laboratory values. Secondary outcome measures include muscle AAV bioactivity; serum GAA bioactivity; glycogen content in muscle, anti-rhGAA antibody formation, muscle status testing by 6 minute walk test, Gross Motor Function Measure, Quick Motor Function Test (QMFT) Measure,Timed up and Go (TUG), and Gait, Stairs, Gower, Chair;and Pulmonary Function Testing.1

The inclusion criteria for the study are individuals diagnosed with Pompe disease via blood or skin fibroblast GAA assay and confirmed with 2 pathogenic variants in the GAA gene, aged 18 years or older at enrollment, capable of providing written informed consent, able to walk at least 100 meters on the 6-minute walk test (with assistive devices allowed), and having forced vital capacity (FVC) within the range of 30% to less than 90% of predicted in the upright position. Additionally, eligible subjects must have confirmed LOPD, have received enzyme replacement therapy ERT for at least 104 weeks immediately preceding screening, and have been on a stable ERT dose for the 52-week period immediately preceding dosing.

The exclusion criteria for the study include individuals requiring invasive or noninvasive ventilation while awake and upright, having FVC less than 20% of predicted in the supine position, receiving a live vaccination within 2 months prior to study Day 1, being pregnant or nursing, having serology consistent with exposure to HIV or active hepatitis A, B, or C infection, having any active liver disease or infection based on clinical symptoms, initiating or discontinuing respiratory muscle strength training within 6 months prior to study Day 1, or unwillingness to continue training for the first year of study participation if training began more than 6 months before study Day 1. Additionally, participants who received an investigational drug or participated in another interventional study within 90 days before Study Day 1, or those planning to participate in another interventional clinical trial within the first 78 weeks after receiving ACTUS-101, are ineligible.

1. AAV2/ 8-LSPhGAA (ACTUS-101) in Late-Onset Pompe Disease. AskBio.
First Patient Dosed with Gene Therapy in Phase 1/2 Study of ACTUS-101 in Patients with Pompe Disease. News release. Ask Bio. January 22, 2019.
3. Smith EC, Hopkins S, Case LE, et al. Phase 1 Study of Gene Therapy in Late-onset Pompe Disease: Initial 104-Week Experience. Presented at: ASGCT 25th Annual Meeting; May 16-19, 2022; Washington DC. Abstract #1211
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