ENB-0040 is an investigational product currently being studied as an enzyme replacement therapy in Phase 2 clinical trials for the treatment of hypophosphatasia (HPP). It is an engineered form of the key enzyme that individuals with HPP lack, is delivered subcutaneously, and is designed to specifically target the patient’s bones.
Enzyme Replacement Therapy to Restore Bone Mineralization
Enzyme replacement therapies (ERTs) work by reintroducing a missing enzyme directly to the diseased target tissue. ENB-0040 is an investigational treatment developed by Enobia Pharma that aims to replace a functional alkaline phosphatase that people with HPP cannot make on their own. ENB-0040 is a recombinant, or genetically engineered, enzyme.
In healthy individuals, the enzyme called tissue non-specific alkaline phosphatase (TNSALP) breaks down inorganic pyrophosphate in the body, which is critical for bone mineralization. The loss of TNSALP in patients with HPP leads to a build up of this compound in the body, which prevents the formation of strong bones and teeth. Treatment with ENB-0040 aims to directly target functional TNSALP to the patient’s bones to help correct this deficiency, leading to restoration of normal bone mineralization.
Scientists have attempted to construct the enzyme in such a way that it is targeted directly to the bone. This ability to target bones will be critical to the success of any therapy for this disease; previous attempts to introduce the missing enzyme have failed because it failed to reach affected bones in sufficient quantities to have a clinical impact.
HPP Clinical Trials
Phase 2 clinical trials are ongoing in infants with hypophosphatasia (HPP) and are planned for children with HPP and adults with HPP-related osteomalacia. A Phase 1 safety trial in adult HPP patients has been completed.
Phase 1 study in adult HPP patients (completed)
Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein (ENB-0040) in Adults with Hypophosphatasia (HPP)
Clinicaltrials.gov ID: NCT00739505
Study design
- One-month, open-label protocol; tested repeat doses.
- Patients received an intravenous infusion of ENB-0040 infusion followed by weekly subcutaneous injections of ENB-0040.
A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of ENB-0040 (Enobia's Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein) in up to 10 Severely Affected Patients With Infantile Hypophosphatasia (HPP)
Clinicaltrials.gov ID: NCT00744042
Study design
- Six-month, open-label protocol involving up to 10 infants with potentially lethal HPP (ages 36 months to six years) with provisions for dose increases based on clinical response and pharmacokinetic (PK) data.
Study of Safety, Efficacy and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) for Treatment of Hypophosphatasia in Children
Clinicaltrials.gov ID: NCT00952484
Study design
- Patients will be randomized to receive subcutaneous injections of either 2 mg/kg or 3 mg/kg ENB-0040 three times weekly for 24 weeks.