Ascendis Pharma reports kidney-function gains sustained for up to five years
A pooled analysis of 139 treated adults showed sustained filtration gains, but long-term follow-up had no continuing placebo comparison.
Adrian Kessler
Kidney-filtration gains persisted for up to five years as Ascendis Pharma A/S NASDAQASND reported pooled follow-up data on Monday for its approved hypoparathyroidism treatment, TransCon PTH. The analysis covered 139 treated adults, but long-term follow-up lacked a continuing placebo comparison.
The Oct. 26 release reported a mean improvement in estimated glomerular filtration rate, or eGFR, of 9.6 mL/min/1.73 m² at one year. The findings add durability evidence for the drug sold as Yorvipath, rather than a new randomized test of kidney protection.
Ascendis is a Copenhagen-based commercial drugmaker focused on rare endocrine diseases, with operations in Europe and the United States. Hypoparathyroidism involves insufficient parathyroid hormone, which regulates calcium and phosphate balance.
Ascendis shares last traded at US$243.37 on Nasdaq at the Oct. 23 close, 4:00 p.m. EDT, according to its linked Google Finance page NASDAQASND. That price precedes Monday's announcement and provides no measure of the market's response.
Filtration Gains Persisted After The First Year
The post-hoc analysis combined the Phase 2 PaTH Forward and Phase 3 PaTHway studies, which enrolled 141 adults. Of those, 139 received the drug and 129 completed their final trial visit.
Placebo-controlled periods lasted four weeks in PaTH Forward and 26 weeks in PaTHway. Open-label extensions continued through weeks 266 and 182, respectively, so the five-year observation window does not apply to every participant.
Patients with eGFR below 30 mL/min/1.73 m² were ineligible. Mean baseline eGFR was 69 mL/min/1.73 m². The increase from baseline was statistically significant from week 26 through trial completion, with p below 0.0001.
Between weeks 52 and 266, the mean annual eGFR slope was positive 0.28 mL/min/1.73 m². That describes maintenance after an early improvement, rather than continuing gains of the initial magnitude.
Mean daily urinary calcium fell from 396 mg at baseline to 170 mg at one year. At their final visits, 98 per cent were independent of active vitamin D and 95 per cent were independent of therapeutic calcium doses.
Ascendis reported no new safety signals, with most treatment-emergent adverse events mild or moderate. The release did not provide adverse-event rates or a placebo-adjusted renal effect for the pooled analysis.
“We are pleased to showcase these benefits of TransCon PTH showing simultaneous improvements across key measures that include maintained normal serum calcium, decreased urine calcium, and sustained increases in eGFR, while enabling independence from conventional therapy,” Ascendis chief medical officer Aimee Shu said.
The filtration findings concern a different kidney measure from the immunologic remission reported in another recent renal study.
Read more: Climb Bio reports 38 per cent immunologic remission in kidney trial
Calcium Control Remains The Regulatory Benchmark
The FDA's account of its Aug. 9, 2024 approval describes a pivotal trial assigning 61 adults to Yorvipath and 21 to placebo. Its composite calcium-control response rate at week 26 was 68.9 per cent versus 4.8 per cent, rather than a kidney-failure endpoint.
The FDA put the response-rate difference at 64.2 percentage points. Its 95 per cent confidence interval ran from 49.5 to 78.8 points.
Kidney biomarkers and clinical outcomes also require separate interpretation in transplant monitoring.
Read more: CareDx links elevated AlloSure Kidney to worse transplant outcomes
The competitors include MBX Biosciences, Inc. NASDAQMBX, which reported one-year open-label findings on June 12 for investigational once-weekly canvuparatide. BridgeBio Pharma, Inc. NASDAQBBIO submitted encaleret to the FDA on May 12 for autosomal dominant hypocalcemia type 1, a distinct genetic condition.
For sector context, the iShares Biotechnology ETF NASDAQIBB closed at US$207.74 on Oct. 23 at 4:00 p.m. EDT, according to its linked Google Finance page.
Ascendis reported second-quarter Yorvipath revenue of €252 million and June 30 cash of €812 million.
Its August outlook targeted a fourth-quarter 2026 Phase 3 start testing TransCon CNP with growth hormone in children with achondroplasia, a separate expansion of its endocrine pipeline.
