A Phase 3, Multicenter, Single Arm, Open-Label Trial, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Japanese Adult Subjects with Hypoparathyroidism - PaTHway Japan Trial

Start Date02 Nov 2021

Sponsor / Collaborator-

NCT04701203 / Active, not recruitingPhase 3

PaTHway TRIAL: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial, With an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults With Hypoparathyroidism

During the first 26 weeks of the trial, participants will be randomly assigned to one of two groups: one group will receive TransCon PTH and one group will receive placebo. All subjects will start with a fixed dose of study drug and will be individually and progressively titrated to an optimal dose over a 10 week period, followed by an individualized dosing period up to 16 weeks. TransCon PTH or placebo will be administered as a subcutaneous injection using a pre-filled injection pen. Neither trial participants nor their doctors will know who has been assigned to each group. After the 26 weeks, participants will continue in the trial as part of a long-term extension study. During the extension, all participants will receive TransCon PTH, with the dose adjusted to their individual needs. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Germany, and Denmark.

Start Date16 Feb 2021

Sponsor / Collaborator

Ascendis Pharma Bone Diseases A/S

CTIS2024-512967-29-00 / Recruiting

PaTH Forward: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel Group Trial with an Open-Label Extension, Investigating the Safety, Tolerability and Efficacy of TransCon PTH Administered Subcutaneously Daily in Adults with Hypoparathyroidism - TransCon PTH TCP-201

Start Date09 Sep 2019

Sponsor / Collaborator

Ascendis Pharma Bone Diseases A/S

100 Clinical Results associated with Palopegteriparatide

100 Translational Medicine associated with Palopegteriparatide

100 Patents (Medical) associated with Palopegteriparatide

Literatures (Medical) associated with Palopegteriparatide

01 Jun 2024·ADVANCES IN THERAPY

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

Article

Author: Tsourdi, Elena ; Imanishi, Yasuo ; Ominsky, Michael S ; Sprague, Stuart ; Zhao, Carol ; Lai, Bryant ; Sibley, Christopher T ; Palermo, Andrea ; Makita, Noriko ; Khan, Aliya A ; Gosmanova, Elvira O ; Rejnmark, Lars ; Rubin, Mishaela R ; Takeuchi, Yasuhiro ; Makara, Michael A ; Kohlmeier, Lynn ; Ukena, Jenny ; Gagnon, Claudia ; Shoback, Dolores M ; Schwarz, Peter ; Shu, Aimee D

INTRODUCTION:

Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism.

METHODS:

PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m².

RESULTS:

At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m² from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m². In participants with baseline eGFR < 60 mL/min/1.73 m², 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m² (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide.

CONCLUSION:

In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT04701203.

30 Apr 2024·Endocrinology and metabolism (Seoul, Korea)

Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone

Review

Author: Rejnmark, Lars

The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

01 Jan 2022·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism

Q2 · MEDICINE

Article

Author: Pagotto, Uberto ; Karpf, David B ; Rubin, Mishaela ; Vokes, Tamara ; Eriksen, Erik ; Palermo, Andrea ; Brod, Meryl ; Clarke, Bart ; Mourya, Sanchita ; Khan, Aliya A ; Smith, Alden ; Schwarz, Peter ; Shu, Aimee D ; Pihl, Susanne ; Rejnmark, Lars ; Marcocci, Claudio ; Markova, Denka ; Hofbauer, Lorenz ; Ahmed, Intekhab

Abstract:

Context:

Hypoparathyroidism is characterized by insufficient levels of parathyroid hormone (PTH). TransCon PTH is an investigational long-acting prodrug of PTH(1-34) for the treatment of hypoparathyroidism.

Objective:

This work aimed to investigate the safety, tolerability, and efficacy of daily TransCon PTH in adults with hypoparathyroidism.

Methods:

This phase 2, randomized, double-blind, placebo-controlled 4-week trial with open-label extension enrolled 59 individuals with hypoparathyroidism. Interventions included TransCon PTH 15, 18, or 21 µg PTH(1-34)/day or placebo for 4 weeks, followed by a 22-week extension during which TransCon PTH dose was titrated (6-60 µg PTH[1-34]/day).

Results:

By Week 26, 91% of participants treated with TransCon PTH achieved independence from standard of care (SoC, defined as active vitamin D = 0 μg/day and calcium [Ca] ≤ 500 mg/day). Mean 24-hour urine Ca (uCa) decreased from a baseline mean of 415 mg/24h to 178 mg/24h by Week 26 (n = 44) while normal serum Ca (sCa) was maintained and serum phosphate and serum calcium-phosphate product fell within the normal range. By Week 26, mean scores on the generic 36-Item Short Form Health Survey domains increased from below normal at baseline to within the normal range. The Hypoparathyroidism Patient Experience Scale symptom and impact scores improved through 26 weeks. TransCon PTH was well tolerated with no treatment-related serious or severe adverse events.

Conclusion:

TransCon PTH enabled independence from oral active vitamin D and reduced Ca supplements (≤ 500 mg/day) for most participants, achieving normal sCa, serum phosphate, uCa, serum calcium-phosphate product, and demonstrating improved health-related quality of life. These results support TransCon PTH as a potential hormone replacement therapy for adults with hypoparathyroidism.

News (Medical) associated with Palopegteriparatide

05 Nov 2024

·www.pharmaceutical-technology.com

Novo Nordisk signs $285m deal with Ascendis to create once-monthly GLP-1RA

The Danish companies aim to jointly develop a GLP-1RA administered once a month. Credit: Kittyfly / Shutterstock Novo Nordisk and Ascendis Pharma have agreed to collaborate in developing metabolic and cardiovascular therapies, among them a once-monthly glucagon-like peptide receptor agonist (GLP-1RA). The collaboration will focus on Novo Nordisk’s obesity and type 2 diabetes products, chief among them a once-monthly GLP-1RA to be developed as the joint venture’s lead candidate. Under the deal’s terms, Novo Nordisk holds exclusive rights to expand resulting metabolic disease products into other therapeutic areas. Novo Nordisk is known globally for its GLP-1RA drug semaglutide, marketed as Wegovy for obesity and Ozempic for type 2 diabetes. The drug is predicted to make $42.85bn in sales in 2030, according to GlobalData. Novo Nordisk’s biggest rival is Eli Lilly’s candidate tirzepatide, marketed as Mounjaro for T2D and Zepbound for obesity, which is predicted to bring in $57.65bn in the same year. A once-monthly drug would be attractive to patients compared to the once-weekly dosing with current alternatives. GlobalData is the parent company of Pharmaceutical Technology. As per the deal signed yesterday (4 November), the two Danish companies will jointly develop therapeutics for metabolic and cardiovascular indications. Ascendis will grant an exclusive, worldwide license for its TransCon technology to Novo Nordisk to develop, manufacture, and commercialise metabolic disease products and product-by-product licenses for those in cardiovascular indications. In return, Ascendis will be eligible to receive total upfront payments from Novo Nordisk of up to $285m, with up to $77.5m in developmental and regulatory milestone payments for each asset concerned as well as sales-based milestone payments and tiered royalties on net sales. Finalisation of the deal depends on regulatory approvals, which both parties seek to achieve by the end of 2024. The TransCon platform allows the transient conjugation of an inert carrier to a parent drug for systemic or local release of a therapeutic payload. Ascendis gained US Food and Drug Administration (FDA) approval for its TransCon-based hypoparathyroidism drug Yorpvipath (palopegteriparatide) in August 2024. In October, the company submitted a supplemental biologics licence application (sBLA) for TransCon hGH, marketed as Skytrofa, to treat growth hormone deficiency. Ascendis stock saw a slight uptick following the disclosure of the deal, rising in value by 1.5% as markets opened on 4 November, adding to the company’s market cap of $7.5bn. According to GlobalData, Ascendis is projected to bring in $508m in global revenue in 2024, set to increase to an annual $4.2bn by 2030. Jan Mikkelesen, Ascendis CEO, said, “The agreement with Novo Nordisk reflects our Vision 2030 to create value in additional large therapeutic areas outside endocrinology rare disease through collaborations with established global leaders.” This deal adds to a collaboration made in 2023 with Teijin Limited, licensing TransCon technology for endocrinological rare diseases, as well as the company’s creation of Eyconis to apply TransCon in ophthalmological indications. Senior Vice President of global research technologies at Novo Nordisk, Brian Vandahl, emphasised the company’s interest in reducing the frequency of therapy delivery and underscored the potential of using the TransCon platform to achieve this.

License out/inDrug Approval

04 Nov 2024

·medcitynews.com

Novo Nordisk Commits $285M to Ascendis to Kick Off Alliance on Longer-Acting GLP-1 Drugs - MedCity News

Novo Nordisk was a pioneer in developing GLP-1 drugs for metabolic disorders, but its products are still mainly once-weekly injections. The Danish pharmaceutical giant is putting up $285 million to begin a strategic alliance granting the pharmaceutical giant access to Ascendis Pharma technology that could develop its drugs for dosing every four weeks. The lead product candidate for the partnership is a once-monthly GLP-1 drug for metabolic indications, but the agreement also includes cardiovascular diseases. Under deal terms announced Monday, Ascendis, which is also based in Denmark, will conduct early development of the product candidates using its TransCon technology. Novo Nordisk will cover the costs of early development and clinical testing. It’s also responsible for regulatory, commercial manufacturing, and commercialization of products stemming from the partnership. TransCon is a platform technology that extends the duration of a drug’s activity in the body, which in turn permits less frequent dosing. The technology already has clinical and regulatory validation through two FDA-approved Ascendis products. Skytrofa, a drug for pediatric growth hormone deficiency, won its FDA nod in 2021. That once-weekly injectable medication was developed as an alternative to daily growth hormone injections. In August, the FDA approved Ascendis’s once-daily injectable Yorvipath as treatment for hypoparathyroidism. Yorvipath provides an alternative to an engineered version of parathyroid hormone that requires multiple injections per day. presented by Health Tech What’s Keeping Healthcare CIOs Up at Night: How to Improve Patient Satisfaction by Handling Calls More Efficiently Health systems have spent billions on portals while investments in modernizing the voice channel — the dominant preference of healthcare consumers — have taken a backseat. By Stephanie Baum The new agreement grants Novo Nordisk an exclusive worldwide license to Ascendis’s technology to develop the pharma giant’s drugs in metabolic diseases. The license for cardiovascular disease drugs is on a product-by-product basis. In a regulatory filing, Ascendis said the collaboration’s lead program aims to develop once-monthly semaglutide, the main pharmaceutical ingredient in the Novo Nordisk GLP-1 products Ozempic, for type 2 diabetes, and Wegovy, for obesity. The license permits Novo Nordisk to use TransCon to develop and commercialize GLP-1 drugs for all indications except for certain rare endocrine indications, indications of the eye and the region around the eye, and cancer. Those exclusions keep the alliance from spreading into areas where Ascendis’s internal pipeline already has product candidates. But Novo Nordisk has exclusive rights to expand any resulting metabolic disease products into other therapeutic areas. Per the regulatory filing, the $285 million sum includes $100 million up front to Ascendis for the exclusive license. The balance is for development and regulatory milestone payments for the lead program. For each additional metabolic or cardiovascular disease drug candidate developed under the alliance, Ascendis could earn up to $77.5 million in development and regulatory milestone payments. It is also eligible for milestone payments and royalties tied to sales of each approved product produced by the collaboration. Novo Nordisk and Ascendis expect to close the deal by the end of this year. “Developing potential therapies that can be administered less frequently could benefit societies as well as individual patients, and it is a clear focus area for Novo Nordisk,” Brian Vandahl, Novo Nordisk senior vice president of global research technologies, said in a prepared statement. “We look forward to working with Ascendis to explore the potential of the TransCon technology platform to reduce the dosing frequency of GLP-1 receptor agonists and other treatments for cardiometabolic diseases.”

License out/inDrug Approval

04 Nov 2024

·www.biopharmadive.com

Novo inks Ascendis deal to develop long-acting GLP-1, other metabolic drugs

Dive Brief:Novo Nordisk is investing further in obesity and metabolic disease, signing a deal to use Ascendis Pharmas delivery technology to advance a long-acting GLP-1 drug as well as develop products in diabetes and cardiovascular conditions, Ascendis said Monday.Per deal terms, Novo could pay up to $285 million in immediate and milestone-based fees to Ascendis for the GLP-1 drug, depending on its progress toward approval. In addition, Ascendis could receive up to $77.5 million for each additional drug developed.Ascendis has won Food and Drug Administration approval of two products using its extended release technology, both in rare conditions. In partnering with Novo, Ascendis would gain entry into conditions that have blockbuster sales potential.Dive Insight:Ascendis claims its drug delivery technology can be tailored to reduce dosing frequency or deliver a therapeutic molecule directly to tissue with disease activity. Its two approved products, Skytrofa for growth hormone deficiency and Yorvipath for hypoparathyroidism, are weekly and daily shots, respectively.In obesity and diabetes, the leading GLP-1 drugs, which include Novos Wegovy and Ozempic, require injections once a week. Novo believes longer-acting agents could help patients stay on their medications. Research released in July showed that more than half of those who initiate GLP-1 treatment discontinue use in just six months.We look forward to working with Ascendis to explore the potential of the TransCon technology platform to reduce the dosing frequency of GLP-1 receptor agonists and other treatments for cardiometabolic diseases, said Brian Vandahl, senior vice president of global research technologies at Novo Nordisk, in a statement.The lead product under the collaboration, which grants Novo an exclusive worldwide license to Ascendis technology, is a once-monthly GLP-1 drug.Ascendis will conduct early development of the drugs developed under the collaboration, with Novo financing that stage of research and assuming clinical, regulatory and commercial development of the drugs.The fees from this collaboration will add to several cash infusions Copenhagen-based Ascendis has received to help fund its operations. In September, Ascendis sold 3% of Yorvipath royalties to Royalty Pharma for $150 million and, later in the same month, sold $281 million in shares following approval of Yorvipath.Despite having two approved products, only one is fully launched. Ascendis lost 240 million euros, or about $262 million, in the first six months of the year. It held 259 million euros in cash as of June 30. '

License out/inFinancial StatementDrug Approval

100 Deals associated with Palopegteriparatide

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Indication	Country/Location	Organization	Date
Hypoparathyroidism	EU	Ascendis Pharma Bone Diseases A/S	17 Nov 2023
Hypoparathyroidism	IS	Ascendis Pharma Bone Diseases A/S	17 Nov 2023
Hypoparathyroidism	LI	Ascendis Pharma Bone Diseases A/S	17 Nov 2023
Hypoparathyroidism	NO	Ascendis Pharma Bone Diseases A/S	17 Nov 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04701203 (FDA_CDER) Manual	Phase 3	Hypoparathyroidism	82	YORVIPATH	kwsctzonxi(heycyiuorq) = izjhqpujot lwivofigxp (oznmeplncr ) View more	Positive	09 Aug 2024
				Placebo	kwsctzonxi(heycyiuorq) = vastjrneoj lwivofigxp (oznmeplncr ) View more
NCT04701203 (PaTHway, Pubmed)	Phase 3	Hypoparathyroidism	82	Palopegteriparatide	rimyomivhp(kzmqprpcvg) = One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide lnjyzasegg (yugxfmsyhd )	Positive	01 Jun 2024
NCT04701203 (PaTHway, GlobeNewswire) Manual	Phase 3	Hypoparathyroidism	82	TransCon PTH (palopegteriparatide)	yedcsgutxw(pgtajrhhbt) = itzmfxdcxh uaggawxysc (qrqtlykqgk ) View more	Positive	13 May 2024
				TransCon PTH (palopegteriparatide) (eGFR < 60 mL/min/1.73m2)	yedcsgutxw(pgtajrhhbt) = luqfuwahby uaggawxysc (qrqtlykqgk ) View more
NCT04009291 (PaTHway \| PaTH Forward, CTgov)	Phase 2	Hypoparathyroidism	59	TransCon PTH (TransCon PTH 15 mcg)	zbwotpvnkp(nspjkfnydy) = myfkerqymy ammkmstyej (cqonqhddhr, vcxwbtybgx - ggqwxwubyw) View more	-	01 Sep 2023
				TransCon PTH (TransCon PTH 18 mcg)	zbwotpvnkp(nspjkfnydy) = otjermjvin ammkmstyej (cqonqhddhr, qgqhvazxup - wtkpqfpbsn) View more
NCT04009291 (PaTH Forward, Corporate Publications) Manual	Phase 2	-	57	TransCon™ PTH	amxeqozbuk(lmmmfdnkjf) = mftzjibijf imkllxlsnp (bqbjlcnfsn ) View more	Positive	12 Sep 2022
NCT04701203 (Corporate Publications) Manual	Phase 3	Hypoparathyroidism	82	Palopegteriparatide	pdkxuqtlwt(tehpmdatig) = mzrwfjytvc nlowvimjtl (rqzdztlhed, 66.3 - 88.1) View more	Positive	13 Mar 2022
				Placebo	pdkxuqtlwt(tehpmdatig) = owqhlmqsbf nlowvimjtl (rqzdztlhed, 0.1 - 23.8) View more
NCT04009291 (PaTH Forward, Pubmed \| J Clin Endocrinol Metab) Manual	Phase 2	Hypoparathyroidism	59	TransCon PTH	txibwopkqp(hytnsqnorh) = sesnzjidur vmepstbcqn (grzzhypweg )	Positive	04 Aug 2021
				TransCon PTH 18 µg PTH(1-34)/day	-
ASN2012	Not Applicable	-	-	PTH	lqpkckbtsj(uxvfhrctqo) = aomqvxivrd kgfezzkodn (vfkoschdep )	-	30 Oct 2012
				FK	lqpkckbtsj(uxvfhrctqo) = wdmiaquvxj kgfezzkodn (vfkoschdep )

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