Ascendis Pharma Seeks FDA Approval for TransCon PTH Phase 2 Trial
Ascendis Pharma is planning to initiate clinical studies to evaluate the potential of its investigational therapy TransCon PTH in adult patients with hypoparathyroidism.
The company has submitted an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA) to start the PaTH Forward Phase 2 trial at up to 40 sites worldwide this year.
The study will examine the safety, tolerability, and early efficacy of TransCon PTH in approximately 40 adult patients with hypoparathyroidism, as well as a possible gradual dose-reduction regimen for complete withdrawal of active vitamin D and calcium supplements.
“Our goal is to control signs and symptoms of hypoparathyroidism in the absence of standard therapies,” Jonathan Leff, MD, chief medical officer of Ascendis Pharma, said in a press release.
Researchers used Ascendis’ proprietary TransCon platform to develop a potential solution to managing the symptoms of hypoparathyroidism while overcoming the limitations of previous therapeutic strategies. TransCon PTH was designed to be a once-daily replacement therapy for hypoparathyroidism with enhanced stability.
TransCon PTH is a long-acting prodrug that when inside the body releases the unmodified active parathyroid hormone in a controlled manner, increasing hormone levels up to within normal range for a 24-hour period. This is expected to normalize blood and urinary calcium levels, serum phosphate levels, and bone turnover.
Data from a Phase 1 clinical trial (ACTRN12617001375347) in 130 healthy adult volunteers supported its target profile as a true replacement therapy for hypoparathyroidism.
The trial was designed to evaluate the safety, tolerability, and overall stability in the body of single or multiple increasing doses of injectable TransCon PTH.
Participants were randomized to receive up to seven single or six multiple ascending doses of TransCon PTH or corresponding placebo. The doses ranged from 3.5 to 124 micrograms for the single-dose groups and 3.5 to 24 micrograms for the multiple-dose groups.
The results showed that daily TransCon PTH injections could effectively increase parathyroid hormone levels to normal range, with a similar 24-hour profile to that achieved with current infusion therapies.
Multiple-dose regimen promoted a dose-dependent, sustained increase in blood calcium levels. Also, treatment with TransCon PTH for 10 days helped control the amount of calcium excreted in the urine, reflecting potent renal calcium reabsorption.
TransCon PTH was generally well-tolerated, with no treatment-related serious or severe adverse events reported. Most common adverse events were minor injection site reactions, likely reflecting the known vasodilatory effects of parathyroid hormone.
“Unlike current therapies for hypoparathyroidism, once-daily TransCon PTH is designed to restore PTH to physiologic levels for 24 hours each day and fully address all aspects of the disease,” Leff said. “With PaTH Forward, we are applying our TransCon technology to advance a new treatment option for patients with this debilitating condition.”
Ascendis Pharma is going to further explore TransCon PTH potential in the new Phase 2 trial in patients with hypoparathyroidism. The trial will introduce a ready-to-use, pre-filled pen to more easily administrate TransCon PTH, and will assess disease-specific patient-reported outcomes. After completing four weeks of treatment, patients can opt to continue taking TransCon PTH in an open-label extension period.
The company expects to announce top-line data from the PaTH Forward trial in the fourth quarter of 2019.