MBX Biosciences: one-year canvuparatide data in hypoparathyroidism
MBX Biosciences has released one-year data from the open-label extension (OLE) of its Phase 2 Avail trial of canvuparatide, a once-weekly parathyroid hormone (PTH) peptide prodrug, in adults with chronic hypoparathyroidism. The Nasdaq-listed company said 57% of evaluable patients achieved responder status at 12 months, broadly consistent with the 63% rate recorded at the 12-week primary endpoint of the controlled phase.
The primary composite endpoint required patients to maintain albumin-adjusted serum calcium within the normal range while remaining independent of active vitamin D and high-dose calcium supplementation. MBX reported no contribution from rescue therapy in the final week of the one-year period, which the company said supports the durability of the response. Of the 64 patients randomised in the controlled trial, 94% elected to continue into the two-year OLE, and 90% of those who entered the extension remained in the study at the one-year mark.
Clinical data in detail
Beyond the responder rate, MBX presented data across several secondary markers. Mean serum calcium was maintained within the normal range throughout 12 months, while 24-hour urinary calcium levels fell from baseline and stayed within normal bounds. Mean estimated glomerular filtration rate, a measure of kidney function, increased from baseline at week 12 and held that improvement through one year, a finding MBX and its clinical advisers characterise as consistent with physiological PTH restoration rather than the supraphysiological calcium loading associated with conventional supplementation.
Bone turnover markers, specifically C-terminal peptide and procollagen type 1 N-terminal propeptide, showed the pattern expected with PTH replacement, and bone mineral density scores were described as consistent with restoration of physiological remodelling. On the pharmacokinetic side, canvuparatide demonstrated a peak-to-trough ratio of approximately 1.3 over a weekly interval and a time to maximum concentration of two to three days, which MBX says supports the once-weekly subcutaneous regimen and differentiates it from daily PTH formulations.
Safety across the OLE was described as generally favourable. Most treatment-emergent adverse events were mild or moderate, no treatment-related serious adverse events were reported, and injection-site reactions occurred in 10% of OLE participants. The company said no new safety signals emerged during the extension period.
Michael T. Collins, Senior Clinical Adviser at the National Institutes of Health and an endocrinologist who participated in the programme, said the pattern of calcium homeostasis, improved kidney function, and bone remodelling observed through one year was "encouraging and consistent with the physiologic effects of restored PTH action."
Market context and competitive landscape
Hypoparathyroidism is estimated to affect more than 250,000 patients in the United States and Europe. The condition carries orphan drug designation in several jurisdictions, including from the FDA for canvuparatide, making it an attractive development target despite its relatively small patient population. The approved PTH replacement landscape is limited: Shire's Natpara (rhPTH 1-84), which received FDA approval in 2015, has faced manufacturing and supply constraints that have kept patient access patchy. A convincing once-weekly peptide prodrug with a stable PK profile could therefore address an unmet need that persists despite an existing approved therapy.
MBX is not alone in pursuing next-generation PTH replacement. A number of companies and academic groups are investigating modified PTH peptides and delivery technologies, though no other once-weekly subcutaneous PTH analogue had reached Phase 3 as of this announcement. The company said its Phase 3 pivotal trial remains on track to initiate in the third quarter of 2026. Investors and clinicians will be watching for the full 12-week Phase 2 dataset, due to be presented at the ENDO 2026 conference on 13 June in Chicago, as the next key read on statistical robustness before the pivotal trial enrols.