Once-weekly therapy may address unmet needs for patients with hypoparathyroidism, phase 2 study suggests
Presenter: Mishaela R. Rubin, MD, Assistant Professor of Clinical Medicine, Columbia University Irving Medical Center, New York, NY
Efficacy and safety of once-weekly canvuparatide in patients with hypoparathyroidism: results from AVAIL, a phase 2 randomized clinical trial. Presented June 13, 2026.
In the AVAIL trial, 63% of participants with hypoparathyroidism receiving the experimental parathyroid hormone peptide prodrug canvuparatide achieved normal serum calcium levels by 12 weeks without active vitamin D therapy and while limiting calcium supplementation to less than 600 mg/day, compared with 31% of participants on placebo (P = .043), according to results presented at ENDO 2026 by Mishaela R. Rubin, MD, of Columbia University.
Dr. Rubin also reported that canvuparatide was generally well tolerated at all dose levels and reduced urinary calcium excretion in most participants. Canvuparatide, given as a once-weekly subcutaneous injection, is designed as a potential long-acting hormone replacement therapy to treat hypoparathyroidism.
“The results from the AVAIL trial are encouraging. A once-weekly therapy could simplify administration and help address important unmet medical needs of patients with hypoparathyroidism,” said Dr. Rubin.
A substantial disease burden
Hypoparathyroidism is a rare endocrine disease, affecting more than 250,000 patients in the United States and Europe. Caused by parathyroid hormone deficiency, it results in hypocalcemia, which can cause symptoms such as muscle cramping or spasm, tingling, and neurologic symptoms such as depression, confusion, and cognitive impairment. More serious complications can include seizures and cardiac arrhythmias.
The current standard of care for hypoparathyroidism requires multiple daily doses of vitamin D supplements and high doses of oral calcium with frequent monitoring; it does not address the underlying cause of the disease.
“Hypoparathyroidism poses a substantial burden to patients, who often face complex treatment regimens and unpredictable swings in calcium levels that can lead to serious complications,” said Dr. Rubin.
Early evidence suggests potential option for unmet need
The AVAIL phase 2 trial was a 12-week, multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of canvuparatide in patients with hypoparathyroidism. It enrolled 64 participants (87.5% female) at 33 locations (27 in the United States, 5 in Argentina, and 1 in Türkiye).
Participants were randomized to receive canvuparatide 400 µg, canvuparatide 600 µg, canvuparatide 800 µg, or placebo. The treatment period included a 4-week fixed-dose period followed by an 8-week titration period during which canvuparatide dosing could be adjusted every 2 weeks in 200-µg increments up to a maximum of 1,600 µg. Forty-eight participants received canvuparatide and 16 received placebo.
The primary composite efficacy endpoint was normalization of albumin-adjusted serum calcium while independent from active vitamin D and calcium supplements (receiving less than 600 mg/day) at 12 weeks. Secondary endpoints included safety and tolerability, urinary calcium excretion, and bone biomarkers. All participants completed the treatment period and 60 (94%) enrolled in the 2-year open-label extension study.
Canvuparatide meets primary endpoint
Compared with placebo, canvuparatide significantly increased the proportions of participants who achieved normal albumin-adjusted serum calcium levels (81% vs 44%, P < .01), remained independent of active vitamin D therapy (98% vs 63%, P < .001), and required no more than 600 mg/day of oral calcium supplementation (75% vs 31%, P < .01).
Mean 24-hour urinary calcium excretion decreased from baseline by 91.8 mg/day in participants receiving canvuparatide, with greater reductions in those with baseline levels of 250 mg/day or higher, in whom it decreased by 203.1 mg/day.
Markers of bone turnover and formation increased in participants receiving canvuparatide: bone-specific alkaline phosphatase levels increased by 12 U/L, C-terminal telopeptide of type I collagen increased by 459 ng/L, and procollagen 1 intact N-terminal propeptide increased by 74 µg/L, compared with minimal changes with placebo.
Most adverse events were mild or moderate. The most common adverse events were headache (which occurred in 21% of canvuparatide recipients vs 6% of placebo recipients), hypercalcemia (19% vs 6%) arthralgia (15% vs 0%), and nausea (13% vs 6%). No deaths or drug-related serious adverse events occurred during the trial. Antidrug antibody incidence was low, occurring only in two patients, who had preexisting antibodies at baseline.
In the open-label extension, 79% of participants receiving canvuparatide kept their serum calcium levels in the normal range (8.2–10.6 mg/dL) and remained independent from conventional therapy (active vitamin D and more than 600 mg/day of calcium supplements) at 6 months.
“The 12-week and 6-month data provide promising early evidence that this investigational therapy may offer a potential option for long-term management, pending further study,” said Dr. Rubin.
Disclosures
No disclosures.
References
Rubin RR, Abbott LG, DiMarchi, RD, et al. Efficacy and safety of once-weekly canvuparatide in patients with hypoparathyroidism: results from AVAIL, a phase 2 randomized clinical trial. Presented at ENDO 2026, June 13, 2026, Chicago, IL.
ClincialTrials.gov. Safety, pharmacokinetics and efficacy of MBX 2109 in patients with hypoparathyroidism. https://clinicaltrials.gov/study/NCT06465108
MBX Biosciences. 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. https://investors.mbxbio.com/news-releases/news-release-details/mbx-biosciences-announces-once-weekly-canvuparatide-achieved