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

NCT06079398 / RecruitingPhase 2

A Phase 2, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial, Evaluating Safety, Tolerability, and Efficacy of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Infants (0 to <2 Years of Age) with Achondroplasia Followed by an Open Label Extension (OLE) Period

This trial is a Phase 2, multicenter, double-blind, randomized (ratio 2:1 TransCon CNP vs. placebo), placebo-controlled trial, designed to evaluate the safety, tolerability, and efficacy of 100 μg CNP/kg of Navepegritide (TransCon CNP) administered SC once-weekly for 52 weeks in infants with genetically verified heterozygous ACH, aged 0 to < 2 years at the time of randomization.

Start Date23 Jan 2024

Sponsor / Collaborator

Ascendis Pharma A/S

100 Clinical Results associated with Navepegritide

100 Translational Medicine associated with Navepegritide

100 Patents (Medical) associated with Navepegritide

Literatures (Medical) associated with Navepegritide

05 May 2024·Cureus Journal of Medical Science

Two Cases of Cardiovascular Adverse Events Following Subcutaneous Vosoritide Injection in Early Infancy

Article

Author: Oda, Yoichiro ; Nishioka, Atsushi ; Adachi, Natsuho ; Tanaka, Hiroyuki

Achondroplasia, characterized by short stature and skeletal abnormalities, is caused by a gain-of-function variant in the fibroblast growth factor receptor 3 gene. Vosoritide, a C-type natriuretic peptide analog, is an emerging treatment for achondroplasia that functions by promoting endochondral ossification. Vosoritide was approved for the treatment of achondroplasia in Europe and the United States in 2021, and in Japan, the following year. However, vosoritide is associated with a risk of hypotension and vomiting after subcutaneous injection due to its vasodilating effect. Herein, we present two cases of cardiovascular adverse events in infants following vosoritide injection. Case 1 involved a one-month-old female infant with achondroplasia who received the first subcutaneous injection of vosoritide 30 minutes after her last formula intake. Following injection, she developed transient symptomatic hypotension accompanied by vomiting. Although established guidelines recommend that injections be administered after approximately 30 minutes (Europe/Japan) or within one hour (USA) following the last feeding, an extended interval of 1.5 to two hours was required to prevent hypotension-associated vomiting. Case 2 involved a three-month-old female infant with achondroplasia. The first subcutaneous vosoritide injection was administered four hours after the last formula intake, and she subsequently developed prolonged compensated shock with marked tachycardia requiring intervention, including repetitive bolus saline injection. These cases indicate the need to monitor patients for cardiovascular adverse events following subcutaneous injection of vosoritide in early infancy.

01 May 2024·EClinicalMedicine

Vosoritide treatment for children with hypochondroplasia: a phase 2 trial

Article

Author: Merchant, Nadia ; Castro, Meryll Grace ; Shafaei, Niusha ; Boucher, Kimberly ; Dauber, Andrew ; Zhang, Anqing ; Dham, Niti ; Seaforth, Raheem ; McCarthy, Tara ; Kanakatti Shankar, Roopa

Background:

Hypochondroplasia is a rare autosomal dominant skeletal dysplasia due to activating variants in FGFR3. It presents with disproportionate short stature with a wide range of clinical severity. There are currently no approved medications to treat short stature in children with hypochondroplasia. Vosoritide is a C-type natriuretic peptide analog that was recently approved for improving growth in children with achondroplasia. We aimed to evaluate the safety and efficacy of vosoritide in children with hypochondroplasia.

Methods:

We conducted a single-arm, phase 2, open-label trial at a single centre in the USA and enrolled 26 children with hypochondroplasia. The trial consists of a 6-month observation period to establish a baseline annualized growth velocity followed by a 12-month intervention period during which vosoritide is administered daily via subcutaneous injection at a dose of 15 μg/kg/day. The trial's co-primary endpoints included the incidence of adverse events and the change from baseline in age-sex standardized annualized growth velocity and height standardized deviation score (SDS) after 12 months of treatment. This trial is registered with ClinicalTrials.gov (NCT04219007).

Findings:

Twenty-four participants with a mean age of 5.86 years received vosoritide therapy. The first participant was enrolled on August 4, 2020, and the final participant completed the 18-month trial on September 8, 2023. Vosoritide was well tolerated with no treatment-related serious adverse events. Injection site reactions occurred in 83.3% of participants. No participants discontinued therapy due to an adverse event. Annualized growth velocity increased by 2.26 standard deviations (SD) and height SDS increased by 0.36 SD during the treatment period versus the observation period. Hypochondroplasia specific height SDS increased by 0.38 SD. There was a 1.81 cm/year increase in absolute annualized growth velocity.

Interpretation:

Vosoritide was safe and effective in increasing growth velocity in children with hypochondroplasia. Efficacy was similar to what has been reported in children with achondroplasia.

Funding:

This study was supported by an investigator-initiated grant from BioMarin Pharmaceutical.

01 Nov 2023·EClinicalMedicine

Once-weekly TransCon CNP (navepegritide) in children with achondroplasia (ACcomplisH): a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-escalation trial

Article

Author: Ma, Nina S ; Zarate, Yuri A ; Savarirayan, Ravi ; Winding, Bent ; Mao, Meng ; Sousa, Sérgio B ; McDonnell, Ciara ; Hoernschemeyer, Daniel G ; Bacino, Carlos A ; Smith, Alden ; Bober, Michael B ; Legare, Janet M ; Volck, Birgitte ; Schnabel, Dirk ; Chakraborty, Mukta ; Ljungberg, Merete ; Hofman, Paul L ; Giwa, Adebola ; White, Klane K ; Högler, Wolfgang ; Shu, Aimee D ; Quattrin, Teresa ; Abuzzahab, M Jennifer

Background:

TransCon CNP (navepegritide) is an investigational prodrug of C-type natriuretic peptide (CNP) designed to allow for continuous CNP exposure with once-weekly dosing. This 52-week phase 2 (ACcomplisH) trial assessed the safety and efficacy of TransCon CNP in children with achondroplasia.

Methods:

ACcomplisH is a global, randomised, double-blind, placebo-controlled, dose-escalation trial. Study participants were recruited between June 10, 2020, and September 24, 2021. Eligible participants were prepubertal, aged 2-10 years, with genetically confirmed achondroplasia, and randomised 3:1 to once-weekly subcutaneous injections of TransCon CNP (6, 20, 50, or 100 μg CNP/kg/week) or placebo for 52 weeks. Primary objectives were safety and annualised growth velocity (AGV). ACcomplisH is registered with ClinicalTrials.gov (NCT04085523) and Eudra (CT 2019-002754-22).

Findings:

Forty-two participants received TransCon CNP at doses of 6 μg (n = 10; 7 female), 20 μg (n = 11; 3 female), 50 μg (n = 10; 3 female), or 100 μg (n = 11; 6 female) CNP/kg/week, with 15 receiving placebo (5 female). Treatment-emergent adverse events (TEAEs) were mild or moderate with no grade 3/4 events reported. There were 2 serious TEAEs that were assessed as not related to TransCon CNP. Eleven injection site reactions occurred in 8 participants receiving TransCon CNP and no symptomatic hypotension occurred. TransCon CNP demonstrated a dose-dependent improvement in AGV. At 52 weeks, TransCon CNP 100 μg CNP/kg/week significantly improved AGV vs placebo (least squares mean [95% CI] 5.42 [4.74-6.11] vs 4.35 [3.75-4.94] cm/year; p = 0.0218), and improved achondroplasia-specific height SDS from baseline (least squares mean [95% CI] 0.22 [0.02-0·41] vs -0·08 [-0.25 to 0.10]; p = 0.0283). All participants completed the randomised period and continued in the ongoing open-label extension period receiving TransCon CNP 100 μg CNP/kg/week.

Interpretation:

This phase 2 trial suggests that TransCon CNP is effective, safe, with low injection site reaction frequency, and may provide a novel, once-weekly treatment option for children with achondroplasia. These results support TransCon CNP at 100 μg CNP/kg/week in the ongoing pivotal trial.

Funding:

Ascendis Pharma, A/S.

News (Medical) associated with Navepegritide

30 Oct 2024

·www.biospace.com

BioMarin Surpasses Analysts’ Q3 Sales Estimates Despite Voxzogo’s Slight Miss

Pictured: BioMarin headquarters in California/iSto iStock , Sundry Photography The biotech beat Wall Street’s third-quarter revenue forecast by 6%, driven by increased uptake of its achondroplasia drug Voxzogo. However, William Blair downgraded BioMarin’s shares to market perform due to a “lack of near-term catalysts” and uncertainty around Voxzogo’s potential revenue growth. BioMarin Pharmaceuticals on Tuesday announced $746 million in total revenue in the third quarter , 28% year-over-year growth driven by the continued strong uptake of its therapies for rare genetic diseases. The biotech beat consensus estimates, surpassing Wall Street’s expected Q3 revenue of $703 million by 6%. BMO Capital Markets analyst Kostas Biliouris in an investor note attributed BioMarin’s strong performance to the continued growth of its achondroplasia medicine Voxzogo, with sales of $190 million jumping 54%. There are now over 3,800 patients on Voxzogo, according to BioMarin, up from around 3,500 in the second quarter . Still, Wall Street anticipated Voxzogo generating $195 million for BioMarin in Q3, a bar the company missed by 3%. Roctavian, a gene therapy approved in June 2023 for hemophilia A , brought in $7 million in the quarter, in line with the analyst consensus. And while its relative contribution to BioMarin’s total Q3 revenue is low, Roctavian presents a high-growth opportunity for the biotech with 600% sales growth versus the same period the year prior. Biliouris said that this “continued uptake” of Roctavian reflects the company’s efforts to focus on the U.S., Italy and Germany markets, potentially paving the way for hitting around $60 million in revenue for the gene therapy by 2025. Truist Securities analyst Joon Lee also credited BioMarin’s Sanofi-partnered enzyme replacement therapy Aldurazyme for its Q3 beat. Sales of Aldurazyme, indicated for mucopolysaccharidosis I, jumped 407% in the quarter bringing in $71 million and beating the consensus expectation of $30 million by $137%. Encouraged by its strong Q3 showing—and by the continued growth of its products—BioMarin on Tuesday raised its full-year 2024 revenue guidance to between $2.79 billion and $2.825 billion. The biotech previously expected a range of $2.75 billion to $2.825 billion this year. Despite BioMarin’s promising outlook for 2024, Lee warned about impending competitive pressure on Voxzogo. Last month, Ascendis Pharma revealed strong pivotal data for its investigational drug TransCon CNP, also known as navepegritide, which showed significant improvements in annual growth velocity in children with achondroplasia. Ascendis is gearing up for a regulatory filing for TransCon CNP in the first quarter of 2025. “In light of better-than-expected data, we’re left to wonder what further impact competition from TransCon-CNP may have on BioMarin’s mid- to long-term guidance,” Lee said. Likewise, William Blair analyst Sami Corwin in a note to investors said that despite the Q3 beat, her firm downgraded shares of BioMarin to market perform. “We do not think its clinical pipeline will be a source of significant value creation in the near term,” according to Corwin. “Voxzogo remains the key top-line growth driver for the company, but the threat of competition could erode its revenue growth and market share.”

Drug Approval

17 Sep 2024

·www.biopharmadive.com

Ascendis trial data piles pressure on BioMarin

BioMarin Pharmaceutical, after months of layoffs, spending cuts and research reorganizations, has staked its futureon the continued success of its approved drug for a common cause of dwarfism. But the San Rafael, California-based biotechnology company could have a new competitor that might complicate those well-laid plans.On Monday, Ascendis Pharma released summary results from a clinical trial testing a treatment that, like BioMarins drug, is designed to treat children with achondroplasia, a skeletal disorder that leads to disproportionate short stature.To analysts on Wall Street, the benefit provided by Ascendis medicine appeared competitive to BioMarins, which was approved in the U.S. three years ago and is still the only available treatment. Ascendis plans to ask the Food and Drug Administration early next year for clearance of its drug, which could set up a regulatory decision and market entry by late 2025 or early 2026.The news sent Ascendis shares up by 17% and pushed BioMarins down by 18% Monday, reflecting Wall Streets reset expectations for how much of the achondroplasia market the latter company may claim with its drug, called Voxzogo.We believe the entry of this competitor into the market could increase investor concerns surrounding the ability for Voxzogo to drive continued top-line growth in a competitive market, Baird analyst Jack Allen wrote in an investor note.Paul Matteis, an analyst at Stifel who has a Buy rating on BioMarin, reduced his teams price target for the companys stock as a result of Ascendis data. We view the drug as clinically equivalent for Voxzogo, he added in a note to clients.The trial results from Ascendis show that its treatment, dubbed TransCon CNP, increased annual growth velocity by significantly more than placebo. The statistical difference between the two groups, measured at one year, was about 1.5 centimeters per year.Ascendis also reported a change in participants annual growth velocity compared to the studys start, allowing for rough comparisons to the data supporting Voxzogos clearance. Among children aged 5 to 11 years, treatment with TransCon CNP led to a placebo-adjusted change in annual growth velocity of 1.78 cm/year. For Voxzogo, the drugs FDA-approved label describes a placebo-adjusted change of 1.57 cm/year.One advantage TransCon CNP could hold, if approved, is in how its dosed. Ascendis drug requires weekly injections, while Voxzogo is taken once daily.[Ascendis] data] demonstrates a profile which suggests safety and efficacy that is comparable to BioMarins Voxzogo with 1/7th the number of injections, wrote Leerink Partners Joseph Schwartz in a client note.Another company that could be affected by Ascendis positive data is BridgeBio Pharma, which is developing a drug called infigratinib. On Tuesday, the company disclosed that the FDA had granted infigratinib a Breakthrough Therapy designation, which it said will help speed its development through an ongoing Phase 3 trial. Shares in the company rose by nearly 5% Tuesday. '

Drug ApprovalClinical ResultPhase 3Breakthrough Therapy

16 Sep 2024

·pipelinereview.com

Pivotal ApproaCH Trial of TransCon™ CNP (Navepegritide) Achieved Primary Objective, Demonstrated AGV Superior to Placebo

– TransCon CNP demonstrated AGV superior to placebo with LS mean treatment difference of 1.49 cm/year at Week 52 (p<0.0001) – For children aged 5-11 years TransCon CNP demonstrated a change from baseline AGV superior to placebo with LS mean treatment difference of 1.78 cm/year at Week 52 (p<0.0001) – Other endpoints supportive that TransCon CNP may provide benefits beyond linear growth – TransCon CNP was generally well-tolerated, with low frequency of injection site reactions (0.41 events per patient year), all mild – Ascendis to host investor conference call Monday, September 16, at 8:00 a.m. E.T. COPENHAGEN, Denmark I September 16, 2024 I Ascendis Pharma A/S (Nasdaq: ASND) today announced topline data from the pivotal double-blind placebo-controlled ApproaCH Trial of TransCon CNP (navepegritide), which included 84 children with achondroplasia (ages 2-11 years) randomized 2:1 (TransCon CNP:placebo). TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP) administered once weekly and designed to provide sustained release and continuous exposure of active CNP. In the trial, children treated with once-weekly TransCon CNP demonstrated annualized growth velocity (AGV) superior to placebo. TransCon CNP also demonstrated statistically significant improvements in other growth parameters, including height Z-score and change from baseline AGV. “Results of this pivotal trial demonstrate that once-weekly TransCon CNP can, if approved, address the need for an efficacious, safe, tolerable, and convenient treatment for children with achondroplasia,” said Ravi Savarirayan, M.D., at the Murdoch Children’s Research Center (Australia) and an investigator in the ApproaCH Trial. “I am excited about the possibilities TransCon CNP presents for a potential new treatment option for these children that will allow decreased injection frequency, improved compliance, and reduced caregiver burden.” “TransCon CNP-treated children with achondroplasia exceeded the growth rate of the general population, suggesting that once-weekly TransCon CNP provides catch-up growth with safety and tolerability results comparable to placebo with a low incidence of injection-site reactions,” said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. “With SKYTROFA ® and TransCon CNP, Ascendis is uniquely positioned to become the leader in the treatment of skeletal dysplasias and growth disorders.” Highlights of the ApproaCH Trial Topline Data Primary Endpoint AGV Change from Baseline Secondary Endpoints Selected Other Endpoints Safety Summary As of today, all 82 children who completed the double-blind period are continuing in the open-label extension of the ApproaCH Trial. “On behalf of everyone at Ascendis, I want to thank the study participants, families, and clinical investigators contributing to the efforts to improve treatment options for individuals living with achondroplasia,” said Aimee Shu, M.D., Ascendis Pharma’s Senior Vice President of Clinical Development, Endocrine & Rare Disease. “These data support our aspirations for TransCon CNP, and we look forward to working with regulatory authorities as we take the next steps to advance TransCon CNP as a potential new treatment option.” Ascendis plans to submit a New Drug Application (NDA) to the U.S. Food & Drug Administration for TransCon CNP for the treatment of children with achondroplasia during the first quarter of 2025 and a Marketing Authorisation Application (MAA) for the treatment of children with achondroplasia to the European Medicines Agency during the third quarter of 2025. ApproaCH is a pivotal, multicenter, randomized, double-blind, placebo-controlled trial of once-weekly TransCon CNP versus placebo in 84 children with achondroplasia ages 2-11 years old. Patients were randomized 2:1 to receive TransCon CNP or placebo for 52 weeks at the 100μg/kg/week dose in the double-blind period, after which all participants could choose to receive TransCon CNP in an ongoing open-label extension at the 100μg/kg/week dose. A slide presentation with these data can be found on the Investor Relations & News section of the Ascendis Pharma website: https://investors.ascendispharma.com . Conference Call & Webcast Information Ascendis Pharma will host a conference call and webcast on Monday, September 16, 2024, at 8:00 am Eastern Time (ET) to discuss the pivotal ApproaCH Trial results. Those who would like to participate may access the live webcast here , or register in advance for the teleconference here . The link to the live webcast will also be available on the Ascendis Pharma Investors & News website at https://investors.ascendispharma.com. A replay of the webcast will be available on this section of the Ascendis Pharma website shortly after conclusion of the event for 30 days. About Ascendis Pharma A/S Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of Patients, Science, and Passion, Ascendis uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more. SOURCE: Ascendis Pharma

Clinical Result

100 Deals associated with Navepegritide

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Achondroplasia	Phase 3	US	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	AU	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	CA	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	DK	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	IE	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	NZ	Ascendis Pharma Growth Disorders A/S	03 Mar 2023
Achondroplasia	Phase 3	ES	Ascendis Pharma Growth Disorders A/S	03 Mar 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05598320 (ApproaCH, PipelineReview) Manual	Phase 2/3	Achondroplasia	84	TransCon CNP (ages 2-11 years)	hrhtuiavqd(cmbouhfzcl) = lolhppjjef yhxyuwtxeh (celhmhdlpy ) View more	Positive	16 Sep 2024
				Placebo (ages 2-11 years)	hrhtuiavqd(cmbouhfzcl) = okqrmxurkx yhxyuwtxeh (celhmhdlpy ) View more
NCT04085523 (ACcomplisH, Company_Website) Manual	Phase 2	Achondroplasia	57	TransCon CNP	wpiblsfdeo(gcpwrcbsba) = patients treated for one year at the pivotal 100μg/kg/week dose demonstrated significant improvements in well-being and physical functioning compared to placebo. mnohtfglai (gunmycunth ) View more	Positive	24 Jun 2024
				Placebo
NCT04085523 (ACcomplisH, CTgov)	Phase 2	Achondroplasia	57	TransCon CNP (TransCon CNP 6 mcg)	gwbzjjmrwc(qutbvnwpsh) = tjwxrzdxhf byemxrtuzx (ogdjqliiig, wjduhccech - takhwlwget) View more	-	07 Mar 2024
				TransCon CNP (TransCon CNP 20 mcg)	gwbzjjmrwc(qutbvnwpsh) = gjuahiqhsv byemxrtuzx (ogdjqliiig, uhwjbimmso - ssiutclixi) View more
ACcomplisH (GlobeNewswire) Manual	Phase 2	Achondroplasia	-	TransCon CNP 100 µg/kg/week	uupkdntjcg(kzoecvthdz): P-Value = 0.002 View more	Positive	20 Dec 2023
				placebo
NCT05246033 (ACcomplisH China, PRNewswire) Manual	Phase 2	Achondroplasia	24	TransCon CNP 50μg/kg/week	psgfupbstt(xecflvjrrh) = qtaiakzwli jnjnqsnpop (ceolfdqcdk ) Met	Positive	16 Nov 2023
				TransCon CNP 100μg/kg/week	psgfupbstt(xecflvjrrh) = trohsslwqi jnjnqsnpop (ceolfdqcdk ) Met
NCT04085523 (ACcomplisH, Pubmed)	Phase 2	Achondroplasia	42	TransCon CNP 100 μg CNP/kg/week	ysawytptco(kfajbvvpxe) = kmrorinjno dyhivrucmb (fyncwdkvwz, 4.74 - 6.11)	Positive	01 Nov 2023
				Placebo	ysawytptco(kfajbvvpxe) = mhnodgbrvk dyhivrucmb (fyncwdkvwz, 3.75 - 4.94)

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Navepegritide

Overview

Basic Info

Gene Sequence

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation