Ascendis Pharma A/S Announces Phase 3 PaTHway Trial of TransCon™ PTH in Adults with Hypoparathyroidism Met Primary and All Key Secondary Endpoints
– For the primary composite endpoint, TransCon PTH demonstrated a response rate of 78.7% compared to 4.8% for control (p-value <0.0001).
– TransCon PTH demonstrated statistically significant improvements compared to control on all key secondary endpoints, which included measures evaluating patient-reported disease symptoms and impacts.
– TransCon PTH was generally well-tolerated, with no discontinuations related to study drug.
– On track to submit NDA during the third quarter and MAA during the fourth quarter of 2022.
– Conference call
“Hypoparathyroidism is an area of major unmet medical need with an estimated 200,000 patients in
Highlights of the Phase 3 PaTHway Trial Top-Line Data
The PaTHway Trial is a Phase 3 double-blind, placebo-controlled trial of 82 dosed adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo).
Primary Composite Endpoint:
- 78.7% of TransCon PTH-treated patients (48 of 61) achieved serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from therapeutic levels of conventional therapy, compared to 4.8% for patients (1 of 21) in control group (p-value = <0.0001).
Key Pre-Specified Secondary Endpoints:
- Statistically significant decrease in patient-reported, disease-specific physical and cognitive symptoms compared to patients in control group, as shown on Hypoparathyroidism Patient Experience Scales (HPES) Symptom-Physical domain scores (p-value = 0.0038) and HPES Symptom-Cognitive domain scores
(p-value = 0.0055).
- Statistically significant reduction in patient-reported disease impact compared to patients in control group, as shown on HPES Impact-Physical Functioning domain scores
(p-value = 0.0046) and HPES Impact-Daily Life domain scores (p-value = 0.0061).
- Statistically significant improvements in patient-reported physical functioning compared to patients in control group, as shown on the SF-36v2® survey Physical Functioning subscale (p-value = 0.0347).
Selected other analyses:
- At Week 26, 95% of TransCon PTH-treated patients were able to discontinue conventional treatments with therapeutic levels of calcium supplements and active vitamin D.
- PaTHway patients had low levels of bone turnover at baseline. TransCon PTH-treated patients demonstrated increased levels of bone turnover markers at Week 26.
- TransCon PTH was generally well tolerated, with no discontinuations related to study drug. Three patients discontinued during the treatment period – 2 from the placebo arm and 1 from the TransCon PTH arm.
- 82% of TransCon PTH patients and 100% of patients in control group reported treatment-emergent adverse events (TEAEs), the majority of which were Grade 1, 2 in severity.
- One serious related TEAE in the TransCon PTH arm was reported due to a dosing error.
- One death in the TransCon PTH arm was assessed as unrelated to study drug.
- TransCon PTH-treated patients showed a mean decrease in 24-hour urine calcium excretion into the normal range, from 390 mg/24 hours down to 220 mg/24 hours. Despite a higher mean serum calcium at Week 26, there was a significantly greater decrease in mean 24-hour urine calcium for TransCon PTH-treated patients compared to patients in control group.
Following an initial blinded study period of 26 weeks, for which top-line data are reported here, all 79 patients completing the blinded period opted to receive treatment with TransCon PTH in the ongoing open-label extension portion of the study for up to 3 years (156 weeks). As of today, all 79 patients continue in the open label extension portion of the PaTHway Trial.
“On behalf of everyone at
Ascendis plans to submit a New Drug Application (NDA) to the
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About TransCon PTH 1
TransCon PTH is an investigational once-daily long-acting prodrug of parathyroid hormone (PTH[1-34]) in development as a treatment for adult hypoparathyroidism (HP). TransCon PTH is designed to restore PTH at physiologic levels for 24 hours each day to address both the short-term symptoms and long-term complications of the disease. TransCon PTH has been granted orphan drug designation in the United States and European Union for the treatment of HP.
About Hypoparathyroidism 2, 3, 4, 5, 6, 7
Hypoparathyroidism (also called “hypopara” or HP) is a rare endocrine disorder characterized by insufficient levels of parathyroid hormone (PTH), resulting in low calcium and elevated phosphate levels in the blood. HP affects approximately 200,000 patients in
Short-term symptoms include weakness, severe muscle cramps (tetany), abnormal sensations such as tingling, burning and numbness (paresthesia), memory loss, impaired judgment, and headache. Patients often experience decreased quality of life, and, over the long term, this complex disorder can increase risk of major complications, such as calcium deposits in the brain, blood vessels, eye, and other soft tissues – including the kidneys, which can lead to impaired renal function.
Current standard of care with active vitamin D and calcium supplements does not fully control the disease and may contribute to risk of renal disease. Patients with HP have an estimated 4-fold to 8-fold greater risk of renal disease compared to healthy populations. The disease is also associated with a 2-fold increased risk of depression or bipolar disorder compared to healthy populations. HP remains among the few hormonal insufficiency states without a replacement therapy that restores the missing hormone at physiologic levels.
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’ plans to submit an NDA and MAA for TransCon PTH, (ii) the expected timing of top-line results for the Phase 3 Pathway Japan Trial, (iii) Ascendis’ plans to initiate a clinical trial of TransCon PTH in pediatric patients with HP, (iv) Ascendis’ ability to apply its platform technology to build a leading, fully integrated biopharma company, and (v) Ascendis’ use of its TransCon technologies to create new and potentially best-in-class therapies. 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 and distributors to supply TransCon hGH, the SKYTROFA® Auto-Injector and other study drug for commercial sales in the
SF-36v2® is a trademark owned by
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1 Karpf DB, et al. J Bone
2 Mannstadt M, et al. Nature Reviews 2017, 3: 17055
4 Hadker N, et al. Endo Pract. 2014, 20(7);671-679
5 Powers J, et al. J Bone
6 Mitchell DM, et al. J Clin Endocrinol Metab 2012, 97(12): 4507-4514
7 Underbjerg L, et al. J Bone
Source: Ascendis Pharma