New weekly therapy moves toward Phase 3 for hypoparathyroidism
Canvuparatide may help normalize calcium levels in rare condition
Written by |
MBX Biosciences is advancing its experimental therapy canvuparatide (MBX 2109) toward a Phase 3 trial in adults with chronic hypoparathyroidism, following a successful End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA).
An End-of-Phase 2 meeting is typically held after a Phase 2 study to determine whether a therapy is ready to move into late-stage testing and to align on the design of the next trial. These meetings help ensure the development program can support a future regulatory application, such as a New Drug Application (NDA).
FDA feedback supports move into Phase 3 testing
The FDA’s feedback supported advancing once-weekly canvuparatide into a Phase 3 trial. The agency and MBX also aligned on key aspects of the study design, including the number of patients, primary and key secondary endpoints, dosing selection, and overall study duration.
According to the company, the Phase 3 trial remains on track to begin in the third quarter of this year. Results from the completed Phase 2 trial, called Avail (NCT06465108), including one-year follow-up data from an ongoing two-year extension study, are expected to be presented at an upcoming medical conference, MBX said.
In parallel, the therapy has been granted orphan drug designation for hypoparathyroidism by the European Medicines Agency, a status intended to support the development of treatments for rare diseases.
“2025 was a year of continued growth and execution for MBX,” Kent Hawryluk, president and CEO of MBX, said in a company press release reporting recent financial results and corporate highlights. “Following a successful End-of-Phase 2 meeting with the FDA, we now have a clear path to initiate our Phase 3 trial of once-weekly canvuparatide.”
Understanding hypoparathyroidism and current treatment limits
Hypoparathyroidism is a rare disorder in which the body produces too little parathyroid hormone (PTH), leading to low calcium and imbalances in other minerals in the blood. Symptoms can range from muscle cramps and fatigue to neurological complications, seizures, kidney problems, and heart issues.
Standard treatment for hypoparathyroidism typically relies on calcium and vitamin D supplements, which help maintain calcium levels but do not fully replace PTH function.
Canvuparatide contains an inactive form of PTH that is converted into its active form once inside the body, mimicking the activity of the naturally occurring hormone. It is given once weekly as a subcutaneous, or under-the-skin, injection.
In Avail, the therapy was tested in 64 adults with chronic hypoparathyroidism who had been taking active vitamin D and at least 800 mg of calcium per day. Participants were randomly assigned to receive either once-weekly canvuparatide at doses of 400, 600, or 800 micrograms, or a placebo, for 12 weeks.
Top-line data showed that canvuparatide normalized blood calcium levels without the need for standard supplement therapy (active vitamin D and more than 600 mg/day of calcium supplements) — the trial’s main goal — in 63% of participants, compared with 31% of those who received the placebo.
The primary outcome was achieved by most participants (79%) after an additional six months of treatment, based on results from the ongoing extension study. Nearly all patients (94%) who completed Avail entered this study, where they either continued canvuparatide or, if they had received the placebo, started treatment.
Phase 3 study will test dosing, safety, and effectiveness
The planned Phase 3 trial will evaluate canvuparatide in approximately 160 adults with chronic hypoparathyroidism. The study will begin with a four-week period in which three out of four participants will receive a fixed dose of 600 micrograms of canvuparatide, while the rest will receive a placebo. This will be followed by an 18-week period during which doses may be adjusted to help keep blood calcium levels in a healthy range, and a final four-week maintenance phase.
The main outcome will be assessed at 26 weeks. After that, participants may enter an extension study to further evaluate the therapy’s long-term safety and effectiveness.
“We believe canvuparatide has the potential to establish a new standard of care in hypoparathyroidism by restoring physiologic PTH activity and maintaining [normal blood calcium levels] with the convenience of a patient-centric once-weekly dosing regimen,” said Sam Azoulay, MD, chief medical officer of MBX in another company press release announcing the successful End-of-Phase 2 FDA meeting.
“Feedback from physicians and patients has reinforced strong interest in a less burdensome treatment option, which we believe should translate into enthusiastic enrollment in the Phase 3 trial, and we look forward to enrolling the first patient in Q3 2026 now that we have confirmed the regulatory path toward an NDA submission,” Azoulay added.
