TransCon PTH brings benefits for up to 1 year in PATHway trial

The therapy is designed to replace PTH missing in hypoparathyroidism

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A graphic highlights the results of a clinical trial.

TransCon PTH treatment continues to show benefits for up to a year in people with hypoparathyroidism, helping them achieve normal blood calcium levels and reducing the need for conventional therapy.

That’s according to new data from PATHway (NCT04701203), a Phase 3 clinical trial wherein Ascendis Pharma is testing the therapy as a once-daily hormone treatment to replace the parathyroid hormone (PTH) that’s missing in hypoparathyroidism.

Just as in the initial (blinded) portion of the trial where TransCon PTH was tested against a placebo for 26 weeks, treatment has been safe and well tolerated and patient-reported symptom and health-related quality of life scores have improved during the 26 weeks of the trial’s ongoing open-label extension.

“We are very pleased to see sustained improvements in clinical outcomes in this trial, including symptom and health-related quality of life measures, consistent with those reported earlier for the initial 26-week blinded portion,” Jan Mikkelsen, Ascendis’ president and CEO, said in a press release.

Bart Clarke, MD, a professor of medicine at the Mayo Clinic in Rochester, presented “Long-Term Efficacy and Safety of TransConTM PTH in Adults with Hypoparathyroidism: 52-Week Results From the Open-Label Extension of the Phase 3 PaTHway Trial” at ENDO 2023, June 15-18 in Chicago.

Hypoparathyroidism occurs when the parathyroid glands produce unusually low amounts of the parathyroid hormone (PTH), leading to decreased calcium and increased phosphate in the bloodstream. An insufficiency of vitamin D, which aids in absorbing calcium, is also seen. This can manifest as weakness, muscle cramps, seizures, unusual tingling sensations, headaches, impaired memory, and mood fluctuations.

Conventional therapy with calcium and active vitamin D supplements can help get calcium within the normal range, “but fails to restore normal PTH physiology [function],” Clarke said.

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What is TransCon PTH ?

TransCon PTH is injected under the skin and is designed to provide a long-lasting precursor of PTH to restore PTH levels for 24 hours. It’s expected to restore calcium levels and reduce the need for conventional therapy.

PATHway is testing how safe and well tolerated it is and how well it works in adults with hypoparathyroidism who were receiving conventional therapy. The trial has two parts: a 26-week blinded portion and a 156-week open-label extension.

Of 82 adults, 79 completed the blinded portion that saw patients receive TransCon PTH or a placebo and entered the extension wherein everyone received TransCon PTH. All except one completed the study’s first 52 weeks.

By week 52, most (81%) patients treated with TransCon PTH achieved normal levels of calcium and reached independence from conventional therapy.

Most (95%) in the open label part also became independent of conventional therapy. This means they no longer needed active vitamin D and were taking less than 600 mg a day of supplemental calcium. “TransCon PTH enabled rapid and sustained independence from conventional therapy,” Clarke said.

TransCon PTH resulted in consistent maintenance of mean albumin-adjusted serum calcium levels within the normal range up to week 52. Albumin-adjusted serum calcium levels refer to the measurement of calcium in the bloodstream that takes into account the concentration of albumin, a protein in the blood.

Patient-reported improvements in physical and cognitive symptoms as well as physical functioning and daily life, measured using the Hypoparathyroidism Patient Experience Scale (HPES), were observed from the start — upon receiving TransCon PTH treatment or after switching from the placebo.

Similar improvements were seen in physical functioning with the 36-Item Short Form Survey (SF-36), a measure of health-related quality of life.

Bone mineral density, a measure of bone health, remained within the levels expected for people of the same age and sex.

TransCon PTH also reduced the amount of calcium being passed to urine each day. This was seen regardless of whether patients had been initially assigned to receive the therapy or a placebo in the trial’s blinded portion.

While most (90%) patients had side effects, they were mild to moderate in severity. Serious side effects were reported by eight (10%) patients. None stopped the treatment due to side effects.

“TransCon PTH continues to be well tolerated in the open-label extension with no new safety signals identified,” Clarke said.

Also ongoing is an open-label extension trial, PaTH Forward (NCT04009291), a Phase 2 study that’s been showing similar long-term benefits in adults.

“These clinical and patient-reported data, and the retention of 145 patients in our ongoing clinical trials, reinforces our confidence that TransCon PTH has the potential, if approved, to benefit adults with hypoparathyroidism regardless of disease etiology,” Mikkelsen said.

Ascendis asked to meet with the U.S. Food and Drug Administration (FDA) earlier this year to discuss TransCon PTH’s approval.