New 4-Year Data Shows Sustained Response to TransCon® PTH (Palopegteriparatide) Therapy in Adults with Hypoparathyroidism

Rhea-AI Summary

Ascendis Pharma (NASDAQ: ASND) released promising 4-year data from its Phase 2 PaTH Forward Trial of TransCon PTH (palopegteriparatide) for adults with hypoparathyroidism. The study demonstrated sustained efficacy with 95% patient retention (56 of 59 patients) at Week 214.

Key findings include: - 98% of patients maintained normal albumin-adjusted serum calcium levels - 93% remained independent from conventional therapy - 67.8% showed clinically meaningful improvement in kidney function (eGFR) - Bone turnover markers stabilized above baseline - Bone mineral density stayed within normal range

The treatment was well-tolerated with mostly mild to moderate adverse events, no serious treatment-related adverse events, and no treatment-related discontinuations.

Positive

• High patient retention rate of 95% after 214 weeks
• 98% of patients maintained normal calcium levels
• 93% of patients achieved independence from conventional therapy
• 67.8% showed clinically meaningful improvement in kidney function
• Strong safety profile with no serious treatment-related adverse events

Negative

• None.

Insights

Endocrinology Specialist

Ascendis' 4-year TransCon PTH data shows impressive 93% of patients off conventional therapy with normalized calcium levels and improved kidney function.

The new 214-week data from Ascendis Pharma's Phase 2 PaTH Forward Trial demonstrates remarkably durable efficacy for TransCon PTH in hypoparathyroidism patients. The 95% retention rate itself speaks volumes about both tolerability and patient satisfaction, as clinical trials typically see much higher dropout rates over such extended periods.

What's particularly impressive is that 93% of patients remained independent from conventional therapy - meaning they no longer required the standard calcium and active vitamin D supplementation that typically burdens these patients. Conventional therapy often leads to complications including hypercalciuria, kidney stones, and soft tissue calcification, so reducing dependency represents a significant clinical advancement.

The normalization of bone turnover markers (CTx and P1NP) indicates restoration of natural bone remodeling processes. In untreated hypoparathyroidism, these markers are typically suppressed, leading to abnormal bone microarchitecture despite often normal or high BMD values. The initial peak followed by stabilization suggests the skeleton is reaching a new homeostasis.

Perhaps most striking is the kidney function improvement, with 67.8% of patients experiencing clinically meaningful increases in eGFR. This suggests TransCon PTH may actually reverse some of the renal damage associated with conventional hypoparathyroidism management - something no other therapy has demonstrated over such a long period.

The clean safety profile with no serious treatment-related adverse events over 4+ years significantly de-risks the long-term commercial prospects for this therapy. For a chronic condition requiring lifelong treatment, this safety record is extraordinarily important.

COPENHAGEN, Denmark, May 12, 2025 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced new data from Week 214 of its Phase 2 PaTH Forward Trial showing that long-term treatment with TransCon PTH (palopegteriparatide) continued to provide a durable response in adults with hypoparathyroidism. Results were shared in an oral presentation today by Andrea Palermo, M.D., from the Campus Bio-Medico University (Rome), during ESPE & ESE 2025, the joint congress of the European Society for Paediatric Endocrinology (ESPE) and the European Society of Endocrinology (ESE).

The PaTH Forward Trial included a 4-week randomized, double-blind, placebo-controlled period followed by an open-label extension period through Week 266. Renal function was assessed by estimated glomerular filtration rate (eGFR). Bone turnover markers C-terminal telopeptide of type 1 collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP), as well as bone mineral density (BMD) measured by DXA scan, were assessed at baseline and regular intervals through Week 214. Safety assessments included 24-hour urine-calcium and treatment-emergent adverse events (TEAEs). At Week 214, 56 of the original 59 patients enrolled (95%) remained in the open-label extension portion of the trial.

At Week 214, nearly all patients (98%) continued to have normal albumin-adjusted serum calcium levels and 93% remained independent from conventional therapy (defined as taking < 600mg/day of calcium and not taking active vitamin D). Bone turnover markers CTx and P1NP increased from the low end of normal at baseline, peaked by Week 26, then declined and remained stable above baseline levels through Week 214. The data also showed continued improvement in skeletal dynamics, with BMD remaining within age- and sex-matched norms. In addition, at Week 214, most participants (67.8%) had a clinically meaningful (≥ 5 mL/min/1.73 m²) increase in eGFR from baseline, with changes in eGFR evident at Week 4.

In the trial, TransCon PTH treatment was generally well-tolerated, with no new safety signals identified. TEAEs were mostly mild or moderate and no serious TEAEs or discontinuations were related to study drug.

“We set out to address the underlying cause of disease and are pleased to see this long-term data reinforcing the safety profile and durability of response in patients treated with TransCon PTH, including sustained normalization of skeletal dynamics and significant and sustained improvements in kidney function,” said Aimee Shu, M.D. Executive Vice President of Endocrine & Rare Disease Medical Science and Chief Medical Officer at Ascendis Pharma.

About Hypoparathyroidism
Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidney and indirectly on the intestine. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune and idiopathic causes.

About Ascendis Pharma A/S
Ascendis Pharma is a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patients, Science, and Passion, and following our algorithm for product innovation, we apply TransCon to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more.

Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, included in this press release regarding Ascendis’ future operations, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to (i) Ascendis’ ability to address the underlying cause of hypoparathyroidism, (ii) Ascendis’ ability to apply its TransCon technology platform to make a meaningful difference for patients, and (iii) Ascendis’ application of its TransCon technologies to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Ascendis makes, including the following: dependence on third party manufacturers, distributors and service providers for Ascendis’ products and product candidates; unforeseen safety or efficacy results in Ascendis’ development programs or on-market products; unforeseen expenses related to commercialization of any approved Ascendis products; unforeseen expenses related to Ascendis’ development programs; unforeseen selling, general and administrative expenses, other research and development expenses and Ascendis’ business generally; delays in the development of its programs related to manufacturing, regulatory requirements, speed of patient recruitment or other unforeseen delays; Ascendis’ ability to obtain additional funding, if needed, to support its business activities; the impact of international economic, political, legal, compliance, social and business factors, including tariffs and trade policies. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Ascendis’ business in general, see Ascendis’ Annual Report on Form 20-F filed with the U.S. Securities and Exchange Commission (SEC) on February 12, 2025, and Ascendis’ other future reports filed with, or submitted to, the SEC. Forward-looking statements do not reflect the potential impact of any future licensing, collaborations, acquisitions, mergers, dispositions, joint ventures, or investments that Ascendis may enter into or make. Ascendis does not assume any obligation to update any forward-looking statements, except as required by law.

Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, and TransCon are trademarks owned by the Ascendis Pharma group. © May 2025 Ascendis Pharma A/S.

Investor Contacts:	Media Contact:
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FAQ

What are the latest clinical trial results for Ascendis Pharma's TransCon PTH (ASND)?

The 4-year Phase 2 PaTH Forward Trial data shows 98% of patients maintained normal calcium levels, 93% achieved independence from conventional therapy, and 67.8% showed improved kidney function, with a 95% patient retention rate.

How effective is TransCon PTH in treating hypoparathyroidism?

TransCon PTH has shown high effectiveness with 98% of patients maintaining normal calcium levels and 93% becoming independent from conventional therapy after 214 weeks of treatment.

What is the safety profile of Ascendis Pharma's TransCon PTH?

TransCon PTH demonstrated a favorable safety profile with mostly mild to moderate adverse events, no serious treatment-related adverse events, and no treatment-related discontinuations.

How does TransCon PTH affect bone health in hypoparathyroidism patients?

The treatment maintained bone mineral density within normal range and stabilized bone turnover markers above baseline levels through Week 214.

What improvements in kidney function were observed with TransCon PTH?

67.8% of patients showed a clinically meaningful improvement in kidney function (eGFR ≥ 5 mL/min/1.73 m²), with changes evident as early as Week 4.