A Phase 2, Open-Label, Single-Arm, 156-week Trial to Investigate the Efficacy, Safety and Tolerability of Combined Once Weekly Navepegritide and Lonapegsomatropin in Children With Achondroplasia

This proof-of-concept trial is being conducted to evaluate the efficacy, safety and tolerability of combination treatment with navepegritide and lonapegsomatropin administered as separate subcutaneous (SC) injections once weekly in children with achondroplasia (ACH) aged 2 to 11 years.

Start Date26 Jul 2024

Sponsor / Collaborator

Ascendis Pharma Growth Disorders A/S

CTIS2023-508341-40-00 / Recruiting

COACH: A Phase 2, Open-Label, Single-Arm, 156-week Trial to Investigate the Efficacy, Safety and Tolerability of Combined Once Weekly Navepegritide and Lonapegsomatropin in Children with Achondroplasia - ASND0042

Start Date26 Jul 2024

Sponsor / Collaborator

Ascendis Pharma Growth Disorders A/S

NCT05775523 / RecruitingNot Applicable

A Prospective, Non-interventional (NIS), Long-term, Post-Authorisation Safety Study (PASS) of Patients Treated With Lonapegsomatropin

The goal of this study is to further characterise the potential long-term safety risks of lonapegsomatropin in patients treated with lonapegsomatropin under real-world conditions in the post-marketing setting.

Start Date20 Mar 2023

Sponsor / Collaborator

Ascendis Pharma Endocrinology Division A/S

100 Clinical Results associated with Lonapegsomatropin-tcgd

100 Translational Medicine associated with Lonapegsomatropin-tcgd

100 Patents (Medical) associated with Lonapegsomatropin-tcgd

Literatures (Medical) associated with Lonapegsomatropin-tcgd

01 Jan 2023·Hormone research in paediatrics

Weekly Growth Hormone (Lonapegsomatropin) Causes Severe Transient Hyperglycemia in a Child with Obesity

Author: Estrada, Doris Elizabeth ; Majidi, Shideh ; Dauber, Andrew ; Alkhatib, Einas H

Introduction: A 12-year-and-9-month-old non-Hispanic black male with a history of growth hormone deficiency, pituitary hypoplasia, prediabetes, obesity, hypertension, and hyperlipidemia was initiated on weekly growth hormone (lonapegsomatropin-tcgd) and then transiently developed symptomatic hyperglycemia to 500 mg/dL. We aimed to describe this medication’s effect. Case Presentation: He was born full term and appropriate for gestational age. He was referred to endocrinology at 3.5 years of age for short stature with a height SDS of −2.48. IGF-1 51.1 ng/mL and IGFBP-3 1.2 ng/mL were low. GH stimulation test noted baseline and peak GH of 0.1 ng/mL. MRI brain showed hypoplastic adenohypophysis, aplastic pituitary stalk, and ectopic neurohypophysis. There had been difficulty with adherence to daily GH over the following 9 years. BMI trajectory rose above 180% of the 95th percentile. By age 12, A1c was 6.6%. Metformin was started and increased to 1,000 mg twice daily. Subsequent A1c was 6.0%. Due to poor compliance with daily GH, at 12 years and 9 months, he was initiated on 22 mg (0.25 mg/kg/week) of weekly lonapegsomatropin-tcgd to improve compliance. The day after his first injection, he developed non-bloody, non-bilious emesis. He denied headaches and endorsed polyuria. Due to concern for increased intracranial pressure, he was sent to the emergency department; however, ophthalmologic exam was negative. Initial serum glucose was 500 mg/dL, then 336 mg/dL after 1-L normal saline. Hemoglobin A1c was 5.7%, urine glucose 3+ mg/dL, and urine ketones 2+ mg/dL. Venous pH of 7.379 and bicarbonate of 20.6 mmol/L ruled out diabetic ketoacidosis. Metformin was held during the hospitalization. Hyperglycemia rapidly improved with transient insulin administration. He received one dose of glargine 20 units. He was initiated on lispro carb ratio of 1:8 and correction factor 1:15 for target glucose 150 mg/dL. By day four, glucoses were below 100 mg/dL; lispro was discontinued, and he was discharged home. Weekly GH was discontinued with plans to resume daily GH therapy in several months. Conclusion: Lonapegsomatropin-tcgd offers the convenience of weekly rather than daily GH treatment; however, this patient developed a rapid increase in insulin resistance and hyperglycemia requiring insulin. The discrepancy between the glucose of 500 mg/dL and A1c of 5.7%, along with the rapid resolution of hyperglycemia, is further consistent with a medication side effect. Close glucose monitoring of patients initiated on weekly growth hormone is crucial, particularly in those with a history of prediabetes.

16 Jun 2022·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

Safety and Efficacy of Lonapegsomatropin in Children With Growth Hormone Deficiency: enliGHten Trial 2-Year Results

Q2 · MEDICINE

Article

Author: Saenger, Paul ; Hofman, Paul L ; Mygind, Per Holse ; Song, Wenjie ; Aghajanova, Elena M ; Maniatis, Aristides K ; Chessler, Steven D ; Mao, Meng ; Nadgir, Ulhas M ; Malievskiy, Oleg ; Beckert, Michael ; Korpal-Szczyrska, Maria ; Chertock, Elena D ; Thornton, Paul S ; Shu, Aimee D ; Komirenko, Allison S ; Vlachopapadopoulou, Elpis ; Smith, Alden R ; Cappa, Marco ; Casella, Samuel J ; Chaychenko, Tetyana

Abstract:

Purpose:

The objectives of the ongoing, Phase 3, open-label extension trial enliGHten are to assess the long-term safety and efficacy of weekly administered long-acting growth hormone lonapegsomatropin in children with growth hormone deficiency.

Methods:

Eligible subjects completing a prior Phase 3 lonapegsomatropin parent trial (heiGHt or fliGHt) were invited to participate. All subjects were treated with lonapegsomatropin. Subjects in the United States switched to the TransCon hGH Auto-Injector when available. Endpoints were long-term safety, annualized height velocity, pharmacodynamics [insulin-like growth factor-1 SD score (SDS) values], and patient- and caregiver-reported assessments of convenience and tolerability.

Results:

Lonapegsomatropin treatment during enliGHten was associated with continued improvements in height SDS through week 104 in treatment-naïve subjects from the heiGHt trial (−2.89 to −1.37 for the lonapegsomatropin group; −3.0 to −1.52 for the daily somatropin group). Height SDS also continued to improve among switch subjects from the fliGHt trial (−1.42 at fliGHt baseline to −0.69 at week 78). After 104 weeks, the average bone age/chronological age ratio for each treatment group was 0.8 (0.1), showing only minimal advancement of bone age relative to chronological age with continued lonapegsomatropin treatment among heiGHt subjects. Fewer local tolerability reactions were reported with the TransCon hGH Auto-Injector compared with syringe/needle.

Conclusions:

Treatment with lonapegsomatropin continued to be safe and well-tolerated, with no new safety signals identified. Children treated with once-weekly lonapegsomatropin showed continued improvement of height SDS through the second year of therapy without excess advancement of bone age.

19 Apr 2022·The Journal of clinical endocrinology and metabolismQ2 · MEDICINE

Response to Letter to the Editor From Malozowski: “Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial”

Q2 · MEDICINE

Letter

Author: Karpf, David B ; Giorgadze, Elene ; Christoffersen, Eva Dam ; Maniatis, Aristides K ; Thornton, Paul S ; Breinholt, Vibeke Miller ; Korpal-Szczyrska, Maria ; Song, Wenjie ; Hofman, Paul L ; Beckert, Michael ; Chertok, Elena ; Lin, Zhengning ; Aghajanova, Elena ; Shu, Aimee D

News (Medical) associated with Lonapegsomatropin-tcgd

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

·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

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

100 Deals associated with Lonapegsomatropin-tcgd

External Link

KEGG	Wiki	ATC	Drug Bank
-	Lonapegsomatropin-tcgd	-	DB16220

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Growth hormone deficiency	US	Ascendis Pharma Endocrinology Division A/S	25 Aug 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endocrine System Diseases	Phase 3	CN	VISEN Pharmaceuticals (Shanghai) Co., Ltd.	30 Dec 2019
Endocrine System Diseases	Phase 3	CN	Ascendis Pharma A/S	30 Dec 2019
Pituitary Diseases	Phase 3	CN	VISEN Pharmaceuticals (Shanghai) Co., Ltd.	30 Dec 2019
Pituitary Diseases	Phase 3	CN	Ascendis Pharma A/S	30 Dec 2019
Achondroplasia	Phase 2	DK	Ascendis Pharma Growth Disorders A/S	26 Jul 2024
Achondroplasia	Phase 2	IE	Ascendis Pharma Growth Disorders A/S	26 Jul 2024
Achondroplasia	Phase 2	GB	Ascendis Pharma Growth Disorders A/S	26 Jul 2024
Turner Syndrome	Phase 2	US	Ascendis Pharma A/S	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03344458 (enliGHten, CTgov)	Phase 3	Growth hormone deficiency	298	Lonapegsomatropin	dwrwzdijav(cjgudkywue) = glrwsmjbpl jfajidnorv (andcryejie, lollgiuwfh - qluvpcjdyu) View more	-	08 May 2024
foresiGHt (Biospace) Manual	Phase 3	Growth hormone deficiency	259	TransCon hGH	jidynmosgf(rlgwucqgap) = srqnzkxzpv ljwniuqkuo (gwrtrafkdg ) View more	Positive	19 Dec 2023
				Placebo	jidynmosgf(rlgwucqgap) = ssnydcdcvd ljwniuqkuo (gwrtrafkdg ) View more
enliGHten (GlobeNewswire) Manual	Not Applicable	Growth hormone deficiency	81	TransCon hGH	ivxyjueljw(adzbqzjpsb) = The most commonly reported adverse events over the course of the trial were categorized as infections, injury, and respiratory/thoracic/medical disorders. The majority of adverse events were mild in severity and unrelated to treatment. No adverse events led to discontinuation of the study treatment. zxtvzqnalz (pnyeukmkec )	Positive	23 Sep 2023
				TransCon hGH (at the beginning of the open-label extension trial)
ESPE2023	Phase 3	Growth hormone deficiency	298	Lonapegsomatropin	ehrnllkrki(psebeirglm) = bikjrcfuaw gubgipngjx (tximkffzgg, 6)	-	21 Sep 2023
NCT04326374 (PRNewswire) Manual	Phase 3	Growth hormone deficiency	150	human growth hormone (Longpei growth promoting hormone group)	crtcuyngzu(dbfsiigmjn) = gsqzotpywu qofxfvlpll (tixougfycr )	Positive	17 Nov 2022
				human growth hormone (growth hormone daily preparation group)	crtcuyngzu(dbfsiigmjn) = madfeilzev qofxfvlpll (tixougfycr )
NCT04326374 (PRNewswire) Manual	Phase 3	Growth hormone deficiency	150	lonapegsomatropin	bxowjsrgcu(rsbderheor): P-Value = 0.0010	Superior	23 May 2022
				daily growth hormone
NCT03305016 (CTgov)	Phase 3	Growth hormone deficiency	146	Lonapegsomatropin	pdlnbcybmz(ymcqnknccd) = hqgujzbzpj apcklwsunc (vtfzmevypu, kswtqmlkxa - clfwsekrgk) View more	-	04 Jan 2022
NCT01947907 (Pubmed \| J Clin Endocrinol Metab) Manual	Phase 2	Growth hormone deficiency	53	TransCon GH	docfpwqqeb(ficvdoghct) = zrqkciango tlqmwhtkqk (bykmlnhxjz )	Positive	01 May 2017
				Genotropin	docfpwqqeb(ficvdoghct) = mhwjmkwnwp tlqmwhtkqk (bykmlnhxjz )
NCT01247675 (CTgov)	Phase 2	Growth hormone deficiency	37	ACP-001 (TransCon hGH) (ACP-001, 0.02 mg hGH/kg/wk)	ihwihkivax(njjqqcsrxu) = osmawwoekr hvyduuoogy (zktfioidiz, tayblnjegl - decrwgmfva) View more	-	09 Mar 2017
				ACP-001 (TransCon hGH) (ACP-001, 0.04 mg hGH/kg/wk)	ihwihkivax(njjqqcsrxu) = sklcexaiiz hvyduuoogy (zktfioidiz, mlmhylafsu - vgdcgmzbkr) View more
NCT01947907 (CTgov)	Phase 2	Growth hormone deficiency	53	ACP-001 (ACP-001, Dose-level 1)	rkfsfsxxsi(fonpqsmays) = undkclzqoo ltxjcrbcns (kzmwiecsuc, lzlxytkcvr - taljqpepjs) View more	-	19 Jan 2017
				ACP-001 (ACP-001, Dose-level 2)	rkfsfsxxsi(fonpqsmays) = tdrgexogwu ltxjcrbcns (kzmwiecsuc, eofhmlfrnv - cwugzyfqpb) View more

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