Summary: In the phase 3 PaTHway trial in adults with chronic hypoparathyroidism, once-daily TransCon PTH (palopegteriparatide) allowed 95% to become independent of conventional calcium and active vitamin D by week 52, with 81% meeting a combined normal-calcium-plus-independence endpoint and urinary calcium roughly halved.
PICO Summary
| Element | Detail |
|---|---|
| Population | 82 adults with chronic hypoparathyroidism (78 completed week 52); 21 sites across North America and Europe. |
| Intervention | TransCon PTH (palopegteriparatide) once daily subcutaneously, titrated to target calcium (open-label extension after a 26-week double-blind period). |
| Comparison | Placebo with conventional therapy (in the preceding double-blind period). |
| Outcome | At week 52: 81% (63/78) met the multicomponent endpoint (normal calcium plus independence from conventional therapy), 95% (74/78) independent of conventional therapy, none needing active vitamin D. 24-hour urinary calcium fell from 376 to 195 mg/day. Bone mineral density Z-scores moved toward norms. Most adverse events mild-moderate; no discontinuations. |
TransCon PTH in hypoparathyroidism (PaTHway)
Phase 3 RCT · chronic hypoparathyroidism · 52 weeks
Once-daily palopegteriparatide freed 95% of adults with chronic hypoparathyroidism from conventional calcium and active vitamin D by week 52 and roughly halved urinary calcium. Long-term renal and skeletal outcomes are still awaited.
Expert Commentary
Hypoparathyroidism is one of the few endocrine deficiencies where, until recently, we treated the consequence with calcium and vitamin D rather than replacing the missing hormone, so a genuine PTH-replacement therapy is conceptually the right fix, and these results are impressive. Freeing 95% of patients from conventional therapy and roughly halving urinary calcium addresses the two things that matter most: symptom burden and the long-term renal damage that chronic hypercalciuria inflicts. My verdict is positive, with measured caveats. These headline figures come substantially from the open-label extension, where everyone knows they are on active drug, so the placebo-controlled contrast is the more conservative anchor; and at 52 weeks we still lack the long-term renal and skeletal outcome data that ultimately justify lifelong replacement. Can I use this with my patients? Yes, for adults with chronic hypoparathyroidism inadequately controlled or burdened by high supplement loads, palopegteriparatide is a rational, disease-modifying option, with careful calcium monitoring during titration. I would still want extended follow-up confirming the urinary-calcium benefit translates into fewer stones and preserved renal function over years.
References
Clarke BL, Khan AA, Rubin MR, et al. Efficacy and safety of TransCon PTH in adults with hypoparathyroidism: 52-week results from the phase 3 PaTHway trial. J Clin Endocrinol Metab. 2025;110(4):951–960. doi:10.1210/clinem/dgae693