MBX Biosciences starts Phase 3 oPTimize trial of once-weekly canvuparatide in chronic hypoparathyroidism, advancing the investigational PTH therapy toward registration.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
MBX Biosciences has dosed the first patient in the pivotal Phase 3 oPTimize trial of once-weekly canvuparatide in adults with chronic hypoparathyroidism (HP), moving the long-acting parathyroid hormone (PTH) replacement into global registrational development. The randomized study will assess whether weekly subcutaneous treatment can restore calcium and mineral homeostasis while reducing patients’ reliance on conventional calcium and active vitamin D supplementation.
Restoring PTH activity
Hypoparathyroidism results from deficient or absent PTH production, leading to hypocalcemia and disrupted regulation of calcium and phosphate metabolism. Standard treatment relies primarily on calcium supplements and active vitamin D, which can control serum calcium but do not replace the missing hormone or fully restore physiologic PTH activity.
Canvuparatide is an investigational long-acting PTH peptide prodrug that provides continuous, infusion-like exposure to active PTH following a once-weekly subcutaneous injection. The program has received Orphan Drug Designation from the U.S. Food and Drug Administration and Orphan Designation from the European Medicines Agency.
Phase 3 oPTimize trial
The global, multicenter Phase 3 oPTimize study (NCT07699471) will enroll approximately 160 adults with chronic HP. Patients will be randomized 3:1 to canvuparatide or placebo during a 26-week double-blind treatment period, followed by a 78-week open-label extension.
Treatment begins with a four-week fixed dose of 600 micrograms once weekly. Patients then enter an 18-week individualized dose-titration period, with doses permitted up to 1,600 micrograms weekly. The final four weeks constitute a maintenance period during which study drug, active vitamin D, and calcium supplementation cannot be increased.
The primary endpoint is a composite responder measure at Week 26. Patients must maintain normal albumin-adjusted serum calcium, become independent of active vitamin D, reduce calcium supplementation to no more than 600 mg/day, and avoid any increase in canvuparatide dose during the preceding four weeks.
Key secondary measures include normalization of urinary calcium in patients with elevated baseline urinary calcium, physical functioning, and hypocalcemia-related symptoms. The study will also assess bone mineral metabolism, kidney health, bone biomarkers, patient-reported outcomes, and long-term safety.
Phase 2 supports pivotal development
The Phase 3 program follows positive findings from the Phase 2 Avail trial and its ongoing open-label extension. Those studies showed changes consistent with restored systemic PTH activity, including normalization of serum calcium, reduced urinary calcium excretion, restoration of bone metabolism, and increased estimated glomerular filtration rate (eGFR).
Importantly, the company reported that clinical benefits remained evident through one year of treatment, providing the rationale for advancing canvuparatide into a registrational study.
Path toward registration
MBX Chairman and CEO Steve Hoerter said the Phase 2 efficacy findings and sustained one-year effects have strengthened the company’s confidence in weekly canvuparatide as a potential new PTH replacement option for chronic HP.
The oPTimize trial now represents the key clinical step toward registration. Its 26-week controlled period will determine whether canvuparatide can deliver durable biochemical control while reducing conventional supplementation, while the long-term extension will provide additional data on safety, symptoms, renal outcomes, and bone health.
Reference
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.