TransCon PTH Normalizes Calcium, Reduces Need for Added Therapies
TransCon PTH normalized calcium levels in the blood and urine of adults with hypoparathyroidism and eliminated the need for vitamin D supplements and high doses of calcium, according to more than 1.5 years of trial data.
This data — 84 weeks’ worth in all — came from the global PaTH Forward Phase 2 trial, which involved 59 hypoparathyroidism patients, and its open-label extension.
“We believe that these data, combined with nearly all patients continuing in the open-label portion of the trial, indicates the potential for TransCon PTH to become the first hormone therapy to replace active vitamin D and therapeutic doses of calcium for adults living with hypoparathyroidism,” Dana Pizzuti, MD, chief medical officer at Ascendis Pharma, the investigational therapy’s developer, said in a press release.
The company also is evaluating TransCon PTH in 76 adults with hypoparathyroidism in the worldwide Phase 3 PaTHway (NCT04701203) trial. Data from this trial are expected early in 2022.
If positive, Ascendis hopes to submit a new drug application or NDA to the U.S. Food and Drug Administration (FDA) later next year seeking regulatory approval for TransCon PTH.
“We look forward to sharing our top-line Phase 3 data in Q1 2022 and, if positive, plan to complete an NDA submission to the FDA in mid-2022,” Pizzuti added.
TransCon PTH is a precursor of the parathyroid hormone, known as PTH, that occurs at low levels in people with hypoparathyroidism. Ascendis’ long-acting investigational therapy is designed to normalize the levels of both calcium and phosphate.
Due to hypoparathyroidism, altered calcium and phosphate levels can lead to generalized weakness, muscle cramps, seizures, and abnormal tingling sensations in the lips, fingers, and toes. It also can cause headaches, memory loss, and mood changes.
The four-week Phase 2 PaTH Forward (NCT04009291) trial assessed the safety and effectiveness of three daily doses of TransCon PTH — 15, 18, or 21 micrograms — given as an under-the-skin injection, compared with a placebo.
TransCon PTH was found to be generally safe and well-tolerated, and 82% of treated patients eliminated the need for conventional therapy — vitamin D supplements and up to 1000 mg of calcium per day.
In addition, 50% of those given the treatment met all of the trial’s primary objectives: the elimination of conventional therapies as well as normalizing the levels of calcium in the blood and urine.
Of the 59 participants in PaTH Forward, all but one, 58, entered the open-label extension study, in which all patients received the therapy. After more than 1.5 years of TransCon PTH treatment, the mean levels of calcium in the blood and urine remained stable and in the normal range.
All study participants stopped vitamin D supplements in the early weeks of the trial and no longer required this conventional therapy. Moreover, 93% of patients were taking 600 mg or less of calcium supplements.
At all doses, TransCon PTH was well-tolerated, with no serious or severe treatment-related events (side effects) reported. In addition, no participants discontinued the study due to treatment-emergent adverse events.
“The continued durable improvements observed in this study over a year and a half of treatment with TransCon PTH highlight the importance of sustained restoration of parathyroid hormone to normal physiological levels,” said Professor Peter Schwarz, MD, professor of endocrinology at Rigshospitalet and Copenhagen University, in Denmark.
“Parathyroid hormone plays an essential role in the regulation of serum and urine calcium and phosphate, thus impacting the function of nerves and muscles, and I am excited that we may potentially soon be able to offer a new treatment paradigm to address the serious health and quality of life issues these patients face each day,” Schwarz added.
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