Canvuparatide normalizes calcium in adults with hypoparathyroidism
Trial achieves primary goal without need for standard supplement therapy
Three months of once-weekly canvuparatide (MBX 2109) normalized blood calcium levels in most adults with chronic hypoparathyroidism, without the need for standard supplement therapy.
That’s according to top-line data from a Phase 2 trial called Avail (NCT06465108), which enrolled 64 adults with chronic hypoparathyroidism who had been taking supplements of active vitamin D and at least 800 mg of calcium per day.
Because the trial met its primary goal of a statistically significant difference in response between the canvuparatide and placebo groups, MBX Biosciences, the therapy’s developer, plans to launch a Phase 3 trial of once-weekly canvuparatide in 2026.
“We are very pleased with the clinically meaningful and statistically significant topline results from our once-weekly canvuparatide Phase 2 trial,” Kent Hawryluk, president and CEO of MBX, said in a company press release. “These data reinforce our conviction that canvuparatide could become a potential best-in-class treatment for hypoparathyroidism.”
‘Hypoparathyroidism poses a substantial burden to patients’
Hypoparathyroidism is a rare disorder characterized by low levels of parathyroid hormone (PTH), a crucial regulator of calcium and phosphorus levels in the body. People with the disorder can experience a range of symptoms, including muscle cramps and spasms, neurological complications, kidney impairment, seizures, and heart problems.
Standard treatment for hypoparathyroidism involves normalizing calcium levels through supplementation with calcium and vitamin D, which helps the body absorb calcium.
Canvuparatide is an inactive version of PTH that is converted to active PTH once inside the body. It is administered once weekly by subcutaneous, or under-the-skin, injection.
“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 trial investigator Mishaela Rubin, MD, professor of medicine at Columbia University in New York. “A once-weekly therapy could simplify administration and help address important unmet medical needs of patients with hypoparathyroidism.”
Calcium levels decreased more with canvuparatide than with a placebo
In a Phase 1 study (NCT05158335), canvuparatide effectively supplied PTH to the bloodstream of healthy adults.
In Avail, participants were randomly assigned to receive either canvuparatide at one of three doses (400, 600, or 800 micrograms) or a placebo for 12 weeks, or approximately three months.
The trial’s primary goal focused on the proportion of patients who maintained blood calcium levels within the normal range with canvuparatide treatment, without the need for standard therapy (active vitamin D and more than 600 mg/day of calcium supplements).
According to top-line data, twice as many adults with hypoparathyroidism who received canvuparatide achieved the primary outcome versus the placebo group (63% vs. 31%).
In secondary measures, among patients with elevated urinary calcium at screening that normalized at week 12, calcium levels decreased more with canvuparatide than with the placebo (48% vs. 33%). In addition, levels of the biomarkers BSAP, CTx, and P1NP indicated enhanced bone remodeling, where old and damaged bone is replaced with new bone, with canvuparatide.
Nearly all patients (94%) who completed Avail started or continued treatment with canvuparatide in a two-year open-label extension study. Most of them (79%) achieved the primary outcome after an additional six months of therapy, including those initially given the placebo.
We are thrilled with these trial results. A once-weekly treatment option that maintains stable calcium control while reducing the day-to-day burden would be a major step forward.
A pharmacokinetic analysis of how the therapy moves into, through, and out of the body confirmed the once-weekly dosing regimen of canvuparatide.
All doses of the therapy were generally well tolerated, and there were no trial discontinuations related to treatment. Most treatment-emergent adverse events were mild or moderate, with no serious adverse events related to canvuparatide reported. More injection site reactions were reported by canvuparatide-treated participants than those in the placebo group (19% vs. 13%).
“We are thrilled with these trial results,” said Patty Keating, executive director of the HypoPARAthyroidism Association. “A once-weekly treatment option that maintains stable calcium control while reducing the day-to-day burden would be a major step forward.”
The company said it will present additional data from the Phase 2 trial and extension study at an upcoming medical meeting.
“These 12-week and 6-month results represent the potential for a meaningful improvement over current treatment options for [hypoparathyroidism] patients and provide a strong foundation for further development,” Hawryluk said. “We look forward to sharing additional once-weekly canvuparatide clinical data at an upcoming medical meeting as we prepare for initiation of our Phase 3 trial.”
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