MBX Biosciences announced today the completion of enrollment in its Phase 2 Avail™ trial evaluating canvuparatide (MBX 2109) for the treatment of chronic hypoparathyroidism. The company has successfully enrolled 64 patients, exceeding its original target of 48 participants.
Canvuparatide is a parathyroid hormone (PTH) peptide prodrug designed to be long-acting and to address the underlying cause of hypoparathyroidism, a rare endocrine disorder affecting approximately 120,000 people in the United States and more than 250,000 across the U.S. and Europe.
"Completion of enrollment in our Phase 2 trial in hypoparathyroidism marks a significant milestone for MBX and brings us closer to our goal of delivering a long-acting PTH therapy designed to treat the underlying disease pathophysiology," said Kent Hawryluk, President and Chief Executive Officer of MBX Biosciences. "We believe canvuparatide could transform the hypoparathyroidism treatment landscape, potentially providing a more consistent therapeutic effect, while offering improved patient convenience and minimizing symptoms associated with large fluctuations in calcium."
Trial Design and Endpoints
The Phase 2 Avail™ trial (NCT06465108) is a randomized, multicenter, 12-week, double-blind, placebo-controlled study evaluating the safety, pharmacokinetics, and efficacy of canvuparatide in adults with hypoparathyroidism.
The primary endpoint of the clinical trial is the proportion of patients who can discontinue active vitamin D and reduce calcium supplements to less than or equal to 600 mg per day after 12 weeks of treatment while maintaining normal serum albumin-adjusted calcium levels (8.2-10.6 mg/dL).
Secondary endpoints include:
- Safety and tolerability of canvuparatide
- Characterization of pharmacokinetics and pharmacodynamic activity
- Measurement of urine calcium, serum phosphorus, 1,25 dihydroxyvitamin D, and bone biomarkers
- Impact on quality of life using patient-reported outcome tools
Top-line results from the Phase 2 Avail trial are expected in the third quarter of 2025.
Understanding Hypoparathyroidism
Hypoparathyroidism is a rare endocrine disease caused by a deficiency of PTH released by the parathyroid glands, resulting in decreased calcium levels in the blood (hypocalcemia). This condition can lead to a variety of acute symptoms, including:
- Muscle cramping or spasm
- Tingling sensations
- Neurological symptoms such as depression, confusion, and cognitive impairment
- More serious complications including seizures and cardiac arrhythmia
The most common cause of hypoparathyroidism, accounting for approximately 75% of cases, is the inadvertent removal of or damage to the parathyroid glands during neck surgery. Other causes include autoimmune processes and genetic conditions.
Current standard of care does not address the underlying PTH deficiency but instead focuses on managing symptoms through high doses of oral calcium supplements and active vitamin D. This approach often leads to inconsistent calcium levels and potential long-term complications.
Innovative Approach to Treatment
Canvuparatide leverages MBX Biosciences' proprietary Precision Endocrine Peptide™ (PEP™) platform technology. The drug was designed to provide:
- Convenient once-weekly administration
- Continuous, infusion-like PTH exposure
- Lower daily peak-to-trough ratios than observed with daily PTH dosing regimens
This approach aims to provide more stable calcium levels while reducing the burden of multiple daily medications. Canvuparatide has received orphan drug designation from the U.S. Food and Drug Administration for the treatment of hypoparathyroidism.
"The current standard of care for hypoparathyroidism patients is inadequate, requiring multiple daily doses of calcium and vitamin D supplements that don't address the underlying hormone deficiency," explained Hawryluk. "Our once-weekly therapy has the potential to significantly improve disease management and quality of life for these patients."
About MBX Biosciences
MBX Biosciences is a clinical-stage biopharmaceutical company based in Carmel, Indiana, focused on the discovery and development of novel precision peptide therapies for the treatment of endocrine and metabolic disorders.
The company's pipeline includes:
- Canvuparatide (MBX 2109) for hypoparathyroidism (Phase 2)
- MBX 1416 for post-bariatric hypoglycemia (Phase 1)
- MBX 4291 and other candidates for obesity (preclinical)
MBX Biosciences' proprietary PEP™ platform was designed to overcome limitations of traditional peptide therapies by creating optimized pharmaceutical properties, including extended time-action profiles, consistent drug concentrations, and less frequent dosing requirements.
As the company moves forward with the Phase 2 trial, the potential for canvuparatide to address a significant unmet need in hypoparathyroidism treatment becomes increasingly promising.
