TransCon PTH improves kidney function at 2 years in PaTHway trial
FDA expected to announce decision on therapy's approval by mid-August
Treatment with Ascendis Pharma’s TransCon PTH (palopegteriparatide) for up to two years leads to sustained improvements in the kidney function of adults with chronic hypoparathyroidism.
That’s according to an analysis of data from PaTHway (NCT04701203), a Phase 3 clinical trial of TransCon PTH. A decision from the U.S. Food and Drug Administration (FDA) as to whether it will approve the therapy is expected by mid-August.
“This unparalleled data showing sustained, clinically meaningful improvements in kidney function in these patients reinforce the potential for TransCon PTH to address concerns about soft-tissue calcifications [calcium deposits] and decreased kidney function associated with conventional therapy,” Aimee Shu, MD, Ascendis Pharma’s senior vice president of clinical development, endocrine medical sciences, said in a company press release.
Peter Schwarz, MD, professor of clinical medicine at the University of Copenhagen presented the results of the two-year follow-up in a presentation, titled “Sustained Improvement in Renal Function With Palopegteriparatide in Adults With Chronic Hypoparathyroidism: 2-Year Results From the Phase 3 PaTHway Trial,” at the recent European Congress of Endocrinology 2024, which took place in Stockholm, Sweden.
Hypoparathyroidism is caused by a shortage of parathyroid hormone, leading to decreased calcium and increased phosphorus levels in the blood. Conventional therapy for hypoparathyroidism involves supplements of calcium and vitamin D, which helps regulate the blood levels of calcium and phosphorus.
TransCon PTH designed to provide precursor of parathyroid hormone
TransCon PTH is designed to provide a long-lasting precursor of parathyroid hormone. The therapy, administered once daily as a subcutaneous (under-the-skin) injection using a pre-filled pen, is expected to restore calcium levels and reduce the need for conventional therapy.
The Phase 3 PaTHway trial is testing the safety and effectiveness of TransCon PTH. The study is divided in two parts: a 26-week (six-month) blinded portion and a 156-week (about three years) open-label extension (OLE).
In the first part, 82 adults with hypoparathyroidism who were receiving conventional therapy were randomly assigned to receive TransCon PTH or a placebo.
Top-line data after six months showed 78.7% of patients treated with TransCon PTH achieved normal levels of calcium in the blood and no longer needed conventional therapy with calcium and vitamin D supplements, classified as vitamin D supplements and up to 600 mg of calcium per day, compared with 4.8% of those on a placebo.
A total of 79 participants who completed the placebo-controlled part of the trial entered the OLE phase wherein all participants received TransCon PTH.
Full, recently published results at one year, showed sustained benefits, while also suggesting improved kidney function with TransCon PTH.
The new two-year analysis (104 weeks) assessed kidney function in 76 patients by measuring changes in their estimated glomerular filtration rate (eGFR) since the start of the study (baseline). eGFR measures how well the small filtering units in the kidneys — the glomeruli — are working to help remove waste and excess fluid from the blood.
eGFR increased in patients on TransCon PTH
Data from patients initially assigned to the placebo showed treatment with TransCon PTH led to a significant mean eGFR increase of 9.4 mL/min/1.73 square meters (m2). In patients on TransCon PTH since the beginning of the study, eGFR increased by a mean of 8.9 mL/min/1.73m2 by week 104.
Clinically meaningful improvements in eGFR, defined as a minimum increase of at least 5 mL/min/1.73 m2, were observed in both groups after six months, with increases sustained for up to two years. In the group originally given the placebo, the proportion of participants with such an improvement in eGFR increased from 24% at six months to 62% after two years, a similar percentage as seen in those on TransCon PTH since the start of PaTHway (61%).
Treatment was generally well tolerated, with no new safety issues reported, according to the press release.
In Europe, data from the placebo-controlled portion of PaTHway supported the therapy’s approval in late 2023. The therapy, under the name Yorvipath, was made available to patients in Germany and Austria a few months later, and has also been approved under the same name in Great Britain.
In April 2023, the FDA decided not to approve the therapy due to concerns over its manufacturing control strategy. According to Ascendis, the company addressed all requests by the FDA and resubmitted its application.
A new decision about the approval in the U.S. is now expected by mid-August, three months later than the previous May 14 deadline.
In the meantime, an expanded access program, which allows doctors to make an online request so that certain patients can obtain the therapy, is ongoing in the U.S.
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