MBX Biosciences is a clinical-stage biopharmaceutical company focused on developing novel precision peptide therapies for metabolic and endocrine diseases. It has announced a promising Phase 2 result from the Avail™ trial evaluating canvuparatide. It is a once-weekly treatment for chronic hypoparathyroidism (HP). The 12-week randomized phase of the trial met its primary endpoint with statistical significance: 63% of patients treated with canvuparatide maintained normal serum calcium levels compared with 31% of the placebo group. Notably, this response was achieved without any rescue treatment. In the open-label extension (OLE), effectiveness continued to improve, with 79% of patients achieving a response status at 6 months, including those initially allocated to the placebo group. All 64 patients finished the initial trial, and 94% transferred to the OLE, reflecting both the potential efficacy and tolerability of the treatment.
Secondary endpoints revealed strong biological activity. Bone markers, such as BSAP, CTx, and P1NP, showed elevated activity consistent with increased bone remodeling. Kidney function markers also showed a benefit, with a 48% reduction in mean urine calcium in canvuparatide-treated patients with increased baseline levels, compared with 33% in the placebo group. Pharmacokinetic results supported a once-weekly dosing regimen, aligning with earlier phase 1 data. These data suggested that canvuparatide can provide continuous PTH-like exposure with decreased variations compared with a daily dosage regimen.
The Avail trial results indicate that canvuparatide is generally well-tolerated. No serious adverse events or discontinuations were reported. Most adverse events were mild to moderate, with injection site reactions occurring in 19% of the treated patients. No deaths were recorded, which highlights the favourable safety profile. The clinical significance is noteworthy, as existing standards of care treatments do not address the underlying PTH deficiency, leaving patients vulnerable to unexpected calcium fluctuations and long-term complications. The results offer a significant advancement by addressing the hormonal deficit at the core of HP.
The company announced a plan to start a Phase 3 clinical trial in 2026 to build a strong naïve for the Phase 2 result. Canvuparatide, also known as MBX 2109, is a parathyroid hormone peptide prodrug developed using the proprietary Precision Endocrine Peptide™ of MBX. It has received orphan drug designation by the U.S. FDA to treat hypoparathyroidism.
The Avail trial (NCT06465108) was a multicenter, randomized, double-blind, placebo-controlled Phase 2 study enrolling 64 patients. Participants were randomized into four groups: canvuparatide at three different dosages (400 µg, 600 µg, and 800 µg once per week by subcutaneous injection) and placebo. The 12-week treatment consisted of a 4-week fixed dosage phase, followed by an 8-week titration phase with 200 µg dose adjustments as needed. Patients who achieved serum calcium normalization without the use of active vitamin D or calcium supplements were considered responders, and these criteria formed the primary endpoint. After completing the trial, 60 patients continued into the two-year OLE, which showed high patient engagement.
Hypoparathyroidism is a rare endocrine disorder affecting about 250,000 people in Europe and the U.S. It is caused by parathyroid hormone deficiency, which leads to hypocalcemia. Symptoms include cognitive impairment, confusion, depression, and neuromuscular issues. Current management relies heavily on a supplement-heavy regimen, which fails to replicate the physiological PTH activity. Canvuparatide represents a potential paradigm shift, offering a physiological and long-acting replacement treatment. With its demonstrated safety profile, effectiveness, and potential to decrease the retreatment burden, canvuparatide has the potential to transform the therapeutic landscape for hypoparathyroidism.
Reference: MBX Biosciences, Inc. Announces Once-Weekly Canvuparatide Achieved Primary Endpoint in Phase 2 Avail Trial and Demonstrated Sustained Improvement Over 6 Months in Open-Label Extension. Published September 22, 2025. Accessed September 23, 2025. MBX Biosciences Announces Once-Weekly Canvuparatide Achieved Primary Endpoint in Phase 2 Trial with 63% Responder Rate at 12 Weeks; 79% Responder Rate at 6 Months in Open-Label Extension
