TransCon PTH Safe, Effective, May Reduce Need for Other Therapies, Trial Data Shows

Marisa Wexler MS avatar

by Marisa Wexler MS |

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TransCon PTH

TransCon PTH, an investigational therapy being developed by Ascendis Pharma, safely normalized calcium and phosphate levels, and reduced the need for other treatments in adults with hypoparathyroidism, data from the PaTH Forward Phase 2 trial demonstrate.

The data were presented by Ascendis investigator Tanja Sikjaer, MD, PhD, at the 2020 European Congress of Endocrinology (ECE), in a presentation titled “TransCon PTH, a Long-acting PTH, in Patients with Hypoparathyroidism: Results of the Phase 2 PaTH Forward Trial.” The ECE is being held virtually Sept. 5-9.

Hypoparathyroidism is characterized by low levels of the parathyroid hormone (PTH), which is important for regulating calcium and phosphate levels in the body. Conventional treatment typically includes supplementing with calcium and active vitamin D.

TransCon PTH was designed to allow the release of a synthetic form of PTH at predefined rates that are controlled by the body’s pH and temperature. This is meant to emulate the activity of naturally occurring PTH, thereby normalizing calcium and phosphate levels and preventing problems such as abnormal bone turnover.

The global PaTH Forward trial (NCT04009291) — sponsored by Ascendis — tested the safety and effectiveness of Transcon PTH in 57 adults with hypoparathyroidism, with an average age of about 50. Most participants (nearly 80%) were women, and a higher proportion were white.

Neck surgery was the most common cause of hypoparathyroidism. To be eligible for the trial, the participants had to be managing their condition with vitamin D analogs (calcitriol at least twice a day or alfacalcidol at least once a day) and calcium supplements —  calcium citrate or calcium carbonate — twice a day or more.

A faster enrollment was established after Natpara (sold by TakedaNatpar in Europe) was recalled in the U.S. over contamination concerns. That move allowed for easier recruitment of individuals who had previously been treated with this therapy.

The participants were given once-daily TransCon PTH at one of three doses (15, 18, or 21 micrograms), or a placebo, for four weeks.

The study’s primary efficacy goal was the percentage of patients who met all four of the following criteria: normal levels of calcium in the blood, no longer needing vitamin D supplements, requiring up to 1,000 mg calcium supplements, and having normalized calcium levels in the urine. A 50% drop in urine calcium also was considered as meeting normal levels.

Collectively, 50% of the participants treated with TransCon PTH met all four criteria. That percentage was significantly higher than the 15% rate seen in the placebo group.

However, when analyzing each treatment dose separately, the scientists found that the difference to placebo was statistically significant only for the highest dose of TransCon PTH (60% vs. 15%).

Notably, 82% of those on TransCon PTH — including all of those on the highest dose — were able to eliminate conventional therapy, which was defined as not requiring vitamin D supplements and needing up to 500 mg of calcium supplements per day.

Among participants given a placebo, 15% were able to eliminate conventional treatment.

TransCon PTH was generally safe and well tolerated, with similar rates of adverse events among participants given the therapy or the placebo. Most treatment-related side effects were mild, and no serious adverse events were reported. No patient had to withdraw treatment due to an adverse event.

“Our presentation of the randomized, double-blind phase 2 PaTH Forward Trial data at this year’s ECE support the use of TransCon PTH as a potential hormone replacement therapy for people living with [hypoparathyroidism],” Aimee Shu, MD, senior medical director of clinical development at Ascendis, said in a press release.

In a separate poster presentation at ECE — titled “Prevalence of Hypoparathyroidism in the EU: A Systematic Review and Meta-analysis” — researchers from Ascendis and BluePrint Orphan performed a comprehensive analysis of published studies to estimate the prevalence of hypoparathyroidism in the European Union. The study was funded by Ascendis.

The results indicated that, in 2018, about 1.1 in every 10,000 people in the EU had hypoparathyroidism that did not develop due to surgery. Meanwhile, 2 in every 10,000 had surgery-related hypoparathyroidism.

Additional analyses indicated that the annual prevalence of post-surgery disease is growing more quickly than that of non-surgical hypoparathyroidism (0.03 vs. 0.01 cases per 10,000). respectively.

“The incidence of post-surgical [hypoparathyroidism] appears to be increasing whereas the incidence of non-surgical [disease] appears to stable,” the researchers wrote. “These results help inform the epidemiology of both non-surgical and post-surgical [hypoparathyroidism] within the EU.”