Last updated Sept. 7, 2022, by Jacob Harney, PhD
 Fact-checked by Patricia Silva, PhD
What is VAL-1221 for Pompe disease?
VAL-1221 is an investigational intravenous (into-the-vein) infusion treatment for Pompe disease that was designed to improve muscle strength and function among people with the rare genetic disorder.
It initially was developed by Valerion Therapeutics, but has since been transferred to a new company called Parasail.
How does VAL-1221 work in Pompe disease?
Pompe is an inherited disease caused by a genetic defect that leads to the deficiency or dysfunction of an enzyme called acid alpha-glucosidase (GAA). This defect allows glycogen — a complex sugar molecule that the GAA enzyme is responsible for breaking down — to accumulate in various cells of the body, primarily in muscle tissues.
The buildup of glycogen disrupts cellular functions and leads to muscle weakness and the potential loss of respiratory function.
The age of disease onset and its severity depend on the extent to which the specific genetic mutation disrupts the functioning of the GAA enzyme.
Enzyme replacement therapy, in which the missing enzyme is supplied to the body externally, is commonly used to treat Pompe and can provide some relief from disease symptoms.
However, after a certain period of time, nearly all patients see a resumed decline in skeletal muscle — muscles responsible for the movements of body parts — and respiratory function.
Excessive amounts of glycogen generated in the course of the disease are stored in cellular compartments called lysosomes, as well as in other parts of the cells (extra-lysosomal storage). Enzyme replacement therapy can reduce the amount of glycogen stored in lysosomes but cannot address the problem associated with extra-lysosomal storage.
VAL-1221 is a fusion protein of Valerion’s proprietary delivery antibody 3E10 with a recombinant human GAA, the missing enzyme in Pompe disease. Due to the presence of the 3E10 antibody, the fusion protein can be delivered to both lysosomal and extra-lysosomal storages of glycogen within cells. In turn, the GAA component of the fusion protein can break down glycogen to reduce its levels inside cells.
How was VAL-1221 administered in Pompe disease?
VAL-1221 has been tested in Pompe as an intravenous infusion, given once every other week. The doses tested include: 3 mg/kg, 10 mg/kg, and 30 mg/kg.
VAL-1221 in Pompe disease clinical trials
Valerion Therapeutics conducted a Phase 1/2 clinical trial (NCT02898753) of VAL-1221 in adults with late-onset Pompe disease, known as LOPD. In this type of Pompe, the onset of disease-related symptoms begins after the age of 1 year.
The randomized, single- and multiple ascending dose-escalation, open-label study was designed to evaluate the safety, tolerability, and preliminary efficacy of VAL-1221. It also tested the medication’s pharmacokinetics — its movement in the body — and its pharmacodynamics, or its effect on the body.
Up to 12 patients were recruited; all were able to walk, did not require a ventilator to breathe, and were being treated with the enzyme replacement therapy Lumizyme.
Results showed dose-dependent improvements in several efficacy outcome parameters. For example, measures of exercise capacity — assessed through the six-minute walk test — showed the average distance walked by patients in six minutes increased by 54 meters in those receiving VAL-1221 (10 or 30 mg/kg). In comparison, control patients who received Lumizyme only saw their average six-minute distance decline by 49 meters.
Efficacy was largely stable with treatment up to 18 months, showing promising results.
According to information provided to Pompe Disease News by Parasail, the therapy’s new developer is seeking financial support to pursue a Phase 3 clinical trial in Pompe disease.
The company also plans to further establish the mechanism of action of VAL-1221, and investigate its therapeutic potential in other glycogen-related diseases that have no existing therapies available (i.e., Lafora disease).
Common side effects of VAL-1221
According to data from the single Phase 1/2 clinical trial, VAL-1221 was generally safe and well-tolerated in patients with late-onset Pompe disease. No serious or unexpected adverse events were reported. Some patients, however, experienced infusion-related adverse events that required a transient dose reduction.
Pompe Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.