New hormone replacement treatment for hypoparathyroidism is safe: Trial
Canvuparatide, tested in healthy adults, found to be long-acting in bloodstream
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Single doses of canvuparatide, an injectable hormone replacement treatment being developed by MBX Biosciences for chronic hypoparathyroidism, appeared to be safe in healthy adults and were long-acting in the bloodstream, supporting the once-weekly dosing regimen now being tested in later-stage trials.
These data come from the first part of a now-completed placebo-controlled Phase 1 clinical study (NCT05158335) and complement the previously published findings from the study’s second part, according to the researchers. Both sets of data showed that subcutaneous, or under-the-skin, injections of canvuparatide were well tolerated and long-acting in healthy people. In the first part, participants received a single injection; in the second part, four once-weekly injections were given.
The developer hopes canvuparatide could offer a more convenient treatment option for people with the hormone-related condition than the once-daily therapies now available.
According to the researchers, “these collective findings support clinical advancement of once-weekly canvuparatide therapy for patients with hypoparathyroidism.”
The study findings were detailed in “Discovery and Characterization of Canvuparatide, a Once-Weekly Parathyroid Hormone Analog for the Treatment of Hypoparathyroidism,” published in the journal Molecular Metabolism. The work was funded by MBX and two of the seven study authors work for the drug developer.
In an also completed Phase 2 clinical study called Avail (NCT06465108), three months of weekly treatment with canvuparatide at one of three doses — 400, 600, or 800 micrograms — was better than a placebo for pushing blood calcium to normal levels among adults with chronic hypoparathyroidism without the need for standard calcium and vitamin D supplements.
MBX is now advancing the therapy into a Phase 3 trial involving adults with chronic hypoparathyroidism. That study is expected to start later this year and is expected to involve approximately 160 adults.
Hypoparathyroidism occurs when the body does not produce enough parathyroid hormone (PTH), which normally controls calcium and phosphorus levels in the blood. As a result, patients often develop low calcium, known as hypocalcemia, and may experience symptoms such as muscle cramps, tingling, and fatigue.
Treatment mainly relies on calcium and active vitamin D supplementation. However, these strategies do not replace the missing PTH and cannot maintain calcium at stable levels over time.
Higher doses led to more canvuparatide in the blood
Canvuparatide, also known as MBX 2109, is an inactive form of the hormone that is gradually converted to an active form once inside the body, mimicking the effects of naturally occurring PTH. While other approved or experimental PTH therapies are designed for daily dosing, canvuparatide is intended to have more sustained effects, enabling once-weekly treatment.
In the first part of the Phase 1 clinical study, 36 healthy adults — 23 men and 13 women, ages 22 to 59 — were randomly assigned to receive a single dose of canvuparatide, ranging from 50 to 600 micrograms, or a placebo. Nearly two-thirds of the study participants were white individuals.
Levels of circulating canvuparatide increased in proportion to the dose: The higher the dose, the more canvuparatide and its active form were present in the blood. Canvuparatide was absorbed slowly, and the active hormone remained in the body for several days, “supporting once-weekly dosing,” the researchers wrote.
Fewer than two-thirds of volunteers — about 60% — reported side effects. These included redness or reactions at the injection site, headache, and temporary high blood calcium. COVID-19 infection was also reported.
All side effects were mild or moderate, and most resolved on their own, according to the researchers. The team said the data support the advancement of canvuparatide “into later phase development for the treatment of hypoparathyroidism.”
Trial data supported by findings of animal studies
The human data are supported by findings in rats and cynomolgus monkeys, where levels of circulating canvuparatide also increased with the dose, and higher doses were linked to more calcium in the blood. In a rat model of hypoparathyroidism, canvuparatide restored calcium to normal levels and increased markers of bone formation, a process that depends on calcium.
