One-Year Canvuparatide Data Support Once-Weekly PTH Replacement Approach in Chronic Hypoparathyroidism

MBX Biosciences has reported one-year data from the ongoing open-label extension (OLE) of its Phase 2 Avail trial, showing sustained clinical benefits for once-weekly canvuparatide in adults with chronic hypoparathyroidism (HP). The findings, presented ahead of ENDO 2026, support the company’s plans to initiate a pivotal phase 3 study in the third quarter of 2026.¹

Chronic HP is a rare endocrine disorder caused by insufficient production of parathyroid hormone (PTH), resulting in hypocalcemia and a range of neuromuscular, cognitive, and cardiovascular complications. Current standard treatment relies on calcium and active vitamin D supplementation but does not replace the missing hormone or fully restore physiologic calcium regulation.²

In the Phase 2 Avail study, 63% of patients receiving canvuparatide achieved the primary composite endpoint at 12 weeks compared with 31% of patients receiving placebo (p=0.042). The endpoint required maintenance of normal serum calcium levels while remaining independent of active vitamin D and requiring no more than 600 mg of daily calcium supplementation. At one year, 57% of evaluable patients maintained responder status without rescue therapy during the final week of treatment.

“These results continue to support the potential of once-weekly canvuparatide to address important unmet needs for patients with hypoparathyroidism,” said Michael T. Collins, MD, endocrinologist and senior clinical advisor at the National Institutes of Health, in a company statement.“The maintenance of calcium homeostasis, increased eGFR, decreased urine calcium and bone remodeling observed through one year are encouraging and consistent with the physiologic effects of restored PTH action.”

What Did the Long-Term Data Show?

Beyond the primary responder analysis, investigators reported evidence consistent with physiologic PTH replacement. Mean serum calcium levels remained within the normal range through one year, while 24-hour urine calcium levels decreased and remained normalized. Improvements in estimated glomerular filtration rate (eGFR), a measure of kidney function, were also maintained throughout the extension study.

Researchers additionally observed changes in bone turnover markers, including C-terminal peptide (CTx) and procollagen type 1 N-terminal propeptide (P1NP), that were consistent with restoration of normal bone remodeling activity.

Pharmacokinetic findings continued to support once-weekly dosing. Canvuparatide demonstrated stable drug exposure with a peak-to-trough ratio of approximately 1.3 and a time to maximum concentration of two to three days, suggesting relatively consistent systemic hormone replacement throughout the dosing interval.¹

Why Is PTH Replacement an Important Goal in Hypoparathyroidism?

Interest in hormone replacement approaches stems from the limitations of conventional therapy. While calcium and vitamin D supplementation can help manage symptoms, they do not fully replicate the physiologic actions of PTH on the kidneys, skeleton, and mineral metabolism. As a result, many patients continue to experience symptoms, impaired quality of life, kidney complications, or abnormal bone metabolism despite treatment.²

Canvuparatide was designed using MBX’s Precision Endocrine Peptide platform to provide continuous, infusion-like PTH exposure with less frequent administration. The therapy has received orphan drug designation from both the US Food and Drug Administration and the European Medicines Agency.³

Safety findings remained consistent with previous reports. No new safety signals were identified during the OLE, most adverse events were mild or moderate, and no treatment-related serious adverse events were reported. Injection-site reactions occurred in 10% of patients. Additionally, 90% of patients entering the extension study remained on treatment after one year, indicating strong long-term retention.

MBX plans to present the one-year OLE results at the 3rd Parathyroid Summit during ENDO 2026 and remains on track to initiate a phase 3 pivotal trial later this year.¹

References

1. MBX Biosciences Announces One-Year Data Demonstrating Sustained Benefit of Once-Weekly Canvuparatide as a Potential PTH Replacement Therapy in Chronic Hypoparathyroidism. (2026 Jun 12). MBX Biosciences. Available at: MBX Biosciences Investor Relations
2. MBX Biosciences Completes Enrollment in Phase 2 Avail Trial of Canvuparatide for Hypoparathyroidism. (2025 Mar 3). Yahoo Finance. https://finance.yahoo.com/news/mbx-biosciences-completes-enrollment-phase-130000129.html
3. EU/3/25/3182 Orphan Designation for Treatment of Hypoparathyroidism. (2026 Jan). European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-25-3182