A Randomized, Double-Blind, Placebo-Controlled, Six-Month Study to Evaluate the Efficacy, Safety and Tolerability of Sarizotan in Patients with Rett Syndrome with Respiratory Symptoms - STARS

Start Date10 Feb 2017

Sponsor / Collaborator

Newron Pharmaceuticals SpA

NCT02790034 / TerminatedPhase 2/3

A Randomised, Double-Blind, Placebo-Controlled 6-month Study to Evaluate the Efficacy, Safety, and Tolerability of Sarizotan in Patients With Rett Syndrome With Respiratory Symptoms

This study evaluates the safety, tolerability and efficacy of Sarizotan in reducing respiratory abnormalities in Rett Syndrome in an initial double blind 24 week period followed by an open label treatment phase of up to 168 weeks (the latter for patients with no safety and tolerability issues).

Start Date26 Oct 2016

Sponsor / Collaborator

Newron Pharmaceuticals SpA

EUCTR2005-000444-84-FI / Not yet recruitingNot Applicable

An open-label, multicenter, multinational Phase III follow-up study to investigate the long-term safety and efficacy of Sarizotan HCl 1 mg b.i.d. in patients with Parkinson's disease suffering from treatment-associated dyskinesia - PADDY-O

Start Date08 Sep 2005

Sponsor / Collaborator

Merck KGaA

100 Clinical Results associated with Sarizotan Hydrochloride

100 Translational Medicine associated with Sarizotan Hydrochloride

100 Patents (Medical) associated with Sarizotan Hydrochloride

Literatures (Medical) associated with Sarizotan Hydrochloride

01 Nov 2024·CNS Drugs

Rett Syndrome: The Emerging Landscape of Treatment Strategies

Review

Author: Percy, Alan K. ; Neul, Jeffrey L. ; Percy, Alan K ; Neul, Jeffrey L ; Ananth, Amitha

Rett syndrome (RTT) has enjoyed remarkable progress in achieving specific therapies. RTT, a unique neurodevelopmental disorder first described in 1966, progressed slowly until the landmark paper of Hagberg and colleagues in 1983. Thereafter, rapid advances were achieved including the development of specific diagnostic criteria and the active search for a genetic etiology, resulting 16 years later in identification of variants in the methyl-CpG-binding protein (MECP2) gene located at Xq28. Shortly thereafter, the NIH Office of Rare Diseases funded the RTT Natural History Study (NHS) in 2003, initiating the acquisition of natural history data on clinical features from a large population of individuals with RTT. This information was essential for advancement of clinical trials to provide specific therapies for this disorder. In the process, the International Rett Syndrome Association (IRSA) was formed (now the International Rett Syndrome Foundation-IRSF), which participated directly in encouraging and expanding enrollment in the NHS and, subsequently, in developing the SCOUT program to facilitate testing of potential therapeutic agents in a mouse model of RTT. The overall objective was to review clinical characteristics developed from the NHS and to discuss the status of specific therapies for this progressive neurodevelopmental disorder. The NHS study provided critical information on RTT: growth, anthropometrics, longevity, key comorbidities including epilepsy, breath abnormalities, gastroesophageal dysfunction, scoliosis and other orthopedic issues, puberty, behavior and anxiety, and progressive motor deterioration including the appearance of parkinsonian features. Phenotype-genotype correlations were noted including the role of X chromosome inactivation. Development of clinical severity and quality of life measures also proved critical for subsequent clinical trials. Further, development of biochemical and neurophysiologic biomarkers offered further endpoints for clinical trials. Initial clinical trials prior to the NHS were ineffective, but advances resulting from the NHS and other studies worldwide promoted significant interest from pharmaceutical firms resulting in several clinical trials. While some of these have been unrewarding such as sarizotan, others have been quite promising including the approval of trofinetide by the FDA in 2023 as the first agent available for specific treatment of RTT. Blarcamesine has been trialed in phase 3 trials, 14 agents have been studied in phase 2 trials, and 7 agents are being evaluated in preclinical/translational studies. A landmark study in 2007 by Guy et al. demonstrated that activation of a normal MECP2 gene in a null mouse model resulted in significant improvement. Gene replacement therapy has advanced through translational studies to two current phase 1/2 clinical trials (Taysha102 and Neurogene-401). Additional genetic therapies are also under study including gene editing, RNA editing, and X-chromosome reactivation. Taken together, progress in understanding and treating RTT over the past 40 years has been remarkable. This suggests that further advances can be expected.

01 Oct 2024·Respiratory Physiology & Neurobiology

Effect of positive allosteric modulation and orthosteric agonism of dopamine D2-like receptors on respiration in mouse models of Rett syndrome

Article

Author: Maletz, Sebastian N ; Reid, Brandon T ; Whitaker-Fornek, Jessica R ; Levitt, Erica S ; Bissonnette, John M ; Arakawa, Keiko ; Bateman, Jordan T ; Baekey, David M

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the methyl-CPG-binding protein 2 (Mecp2) gene. Frequent apneas and irregular breathing are prevalent in RTT, and also occur in rodent models of the disorder, including Mecp2^Bird and Mecp2^R168X mice. Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). Targeting the 5HT1a receptor alone also improves respiration in RTT mice (Levitt et al., 2013). However, the contribution of D2-like receptors in correcting these respiratory disturbances remains untested. PAOPA, a dopamine D2-like receptor positive allosteric modulator, and quinpirole, a dopamine D2-like receptor orthosteric agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2-like receptors is sufficient to improve breathing disturbances in female heterozygous Mecp2^Bird/+ and Mecp2^R168X/+ mice. PAOPA did not significantly change apnea incidence or irregularity score in RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO₂). In contrast, quinpirole reduced apnea incidence and irregularity scores and improved the hypercapnic ventilatory response in Mecp2^R168X/+ and Mecp2^Bird/+ mice, while also reducing respiratory rate. These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects.

07 Jul 2023·The Journal of organic chemistry

Tandem InCl₃-Promoted Hydroperoxide Rearrangements and Nucleophilic Additions: A Straightforward Entry to Benzoxacycles.

Article

Author: Gayraud, Oscar ; Cheibas, Cristina ; Fayet, Agathe ; Frison, Gilles ; Bosnidou, Alexandra E ; Nay, Bastien ; Bourcier, Sophie

The acid-catalyzed rearrangement of organic peroxides is generally associated with C-C-bond cleavages (Hock and Criegee rearrangements), with the concomitant formation of an oxocarbenium intermediate. This article describes the tandem process between a Hock or Criegee oxidative cleavage and a nucleophilic addition onto the oxocarbenium species (in particular a Hosomi-Sakurai-type allylation), under InCl₃ catalysis. It was applied to the synthesis of 2-substituted benzoxacycles (chromanes and benzoxepanes), including a synthesis of the 2-(aminomethyl)chromane part of sarizotan, and a total synthesis of erythrococcamide B.

News (Medical) associated with Sarizotan Hydrochloride

08 Jun 2021

·endpts.com

A gene therapy biotech is bursting onto the scene with 12 programs in tow. An ultra-rare neuro disease is up first

In downtown Lowell, MA, tucked into one of the country’s oldest surviving textile mill complexes is a new biotech toiling away on next-gen CNS therapies for severe neurological disorders. And it’s starting with Rett syndrome — a rare neurodevelopmental condition that almost exclusively affects girls. Kathrin Meyer Alcyone Therapeutics emerged from stealth mode Wednesday with $23 million from RTW Investments and 12 new gene therapy programs in the works. The company was created last summer, shortly after founder and CEO PJ Anand met Kathrin Meyer, a principal investigator in the gene therapy unit at the Abigail Wexner Research Institute at Nationwide Children’s Hospital. “We decided that there was so much mutual synergy,” Anand told Endpoints News, leading them to execute a collaboration last year. The company plans on filing an IND this year for one of its lead candidates, ACTX-101 — a Rett syndrome treatment using X-reactivation technology. Its other lead candidate, ACTX-401, is a gene therapy for spinal muscular atrophy with respiratory distress type 1 (SMARD1). Researchers at the Baylor College of Medicine identified mutations in a gene called MECP2 as the cause of Rett syndrome back in 1999. The disorder causes severe impairments that affect a child’s ability to speak, walk, eat and breathe easily, a common sign being constant repetitive hand movements. The challenge with conventional transgene replacement, Anand explained, is that overproduction of MECP2 is just as bad as underproduction. “It is one of those Goldilocks indications where you want to have the right amount of protein,” he said. “The potential of this platform is to increase the efficiency of gene therapy not by 1 time or 2 times, but my multiple times.” Alcyone is coupling its precise CNS delivery platform with X-chromosome reactivation technology, so instead of just replacing the gene in the active X-chromosome (and risking overexpression of MECP2), they’re selectively reactivating areas in the inactive X-chromosome to get MECP2 production. Anand has big plans to make this program a “pipeline in a product,” where the same gene product can be applied to other X-chromosome-related syndromes. Prior to this, he founded Anuncia, a spinoff looking to treat hydrocephalus and cerebrospinal fluid dysfunctions, and co-founded the medical device company Arthromeda. Alcyone’s joining a host of other companies on the hunt for the first Rett syndrome therapy, including New York biotech Anavex, which got fast track status for its blarcamesine back in 2020. Acadia Pharmaceuticals, maker of the Parkinson’s disease drug Nuplazid, entered its trofinetide in a pivotal Phase III study for Rett syndrome in late 2019. Newron Pharmaceuticals dropped out of the race last May, culling its Rett syndrome program after sarizotan failed a Phase II/III trial. The 35-person team at Alcyone is also developing candidates using conventional transgene replacement, vectorized exon skipping and promotor modulation. “Our next-generation precision delivery platform shows strong potential in overcoming the fundamental challenge in CNS therapy development,” Anand said.

Gene TherapyFast Track

30 Apr 2015

·www.biospace.com

Newron Pharmaceuticals Completes CHF24.3M/US$25.5 Million In Private Placement From Leading EU And US Investors

- Funding Set to Accelerate Clinical Development of Novel Medicines for Rare Central Nervous System Disorders - MILAN--(BUSINESS WIRE)--Newron Pharmaceuticals S.p.A. (“Newron”), a research and development company focused on novel CNS and pain therapies, announces that it has completed a capital increase raising gross proceeds of CHF24.3 million/US$ 25.5 million, following the subscription by institutional investors of 843,072 newly issued shares. The capital increase was approved at the Company’s Extraordinary Shareholder’s Meeting on March 24, 2015. Once issued, the new shares will be immediately and freely tradable. “The funds raised will enable us to accelerate the development of sarizotan in Rett Syndrome and of NW-3509, a highly innovative add-on therapy for schizophrenia, for which we plan to start a Phase II study in Q3 2015.” The fundraising was supported by current institutional shareholders and institutional investors from Europe and the U.S., including Aviva, J.P. Morgan Asset Management, Investor AB, Sphera Global HealthCare Fund and Nyenburgh. The subscription price was set at CHF 28.80 per share, slightly below the closing price of Newron’s shares on April 27, 2015, of CHF29.60. The net proceeds from the fundraising will be used to accelerate the development of Newron’s pipeline of innovative CNS therapeutics, primarily sarizotan for patients with Rett Syndrome, as well as NW-3509, a novel antipsychotic for patients with positive symptoms of schizophrenia. Additional compounds in development include sNN0031 for patients with Parkinson’s disease who no longer respond to oral therapy and sNN0029 for patients with Amyotrophic Lateral Sclerosis (ALS). Stefan Weber, CEO of Newron, commented: “With Xadago® (safinamide) approved in the EU, where it will shortly be launched in the first member states by our partner Zambon, and with the U.S. NDA under FDA review for marketing authorization, Newron’s focus is now on expediting development of its highly promising CNS orphan compounds for which it holds the commercial rights. We thank existing and new shareholders for their support of Newron’s strategy for sustainable growth.” Roberto Galli, Newron’s VP Finance, added: “The funds raised will enable us to accelerate the development of sarizotan in Rett Syndrome and of NW-3509, a highly innovative add-on therapy for schizophrenia, for which we plan to start a Phase II study in Q3 2015.” Closing of the transaction will be subject to customary Italian and Swiss regulatory requirements. The new shares will be listed and traded on the SIX Swiss Exchange under the same ISIN as the Company’s existing shares (ISIN: IT0004147952) on or around May 6, 2015. Bank am Bellevue and WG Partners acted as advisors to Newron in connection with the transaction. About Newron PharmaceuticalsNewron (SIX: NWRN) is a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central nervous system (CNS) and pain. The Company is headquartered in Bresso near Milan, Italy. Marketing authorization in the EU for Xadago® (safinamide) was granted by the EU Commission in February 2015, following the recommendation by the Committee for Medicinal Products for Human Use (CHMP) to approve the compound in the EU on Dec. 19, 2014. The New Drug Application NDA to the U.S. FDA, as informed early March, has been accepted for filing, after being re-submitted by Newron on Dec. 26, 2014. In March 2014, Zambon, a partner of Newron, submitted a MAA to Swissmedic. Zambon has the rights to develop and commercialize safinamide globally, excluding Japan and other key Asian territories where Meiji Seika has the rights to develop and commercialize the compound. Newron’s additional projects are based on highly promising treatments for rare disease patients and are at various stages of clinical development, including sarizotan for patients with Rett syndrome, sNN0031 for patients with Parkinson’s disease, non-responsive to oral drug treatments, sNN0029 for patients with ALS and ralfinamide for patients with specific rare pain indications. Newron is also developing NW-3509 as the potential first add-on therapy for the treatment of patients with positive symptoms of schizophrenia. Important NoticesThis document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates and current and future collaborations for the development and commercialisation of its product candidates and reduce costs (including staff costs), (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s anticipated future revenues, capital expenditures and financial resources, and (4) assumptions underlying any such statements. In some cases these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. All statements, other than historical facts, contained herein regarding Newron's strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron's research programmes, development activities, commercialisation plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly up-date or revise forward looking statements except as may be required by applicable regulations of the SIX Swiss Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever. Contacts MediaNewron PharmaceuticalsStefan Weber, CEO, +39 02 6103 46 26pr@newron.comorUK/EuropeFTI ConsultingJulia Phillips, +44 (0)20 3727 1000orSwitzerlandIRF CommunicationsMartin Meier-Pfister, +41 43 244 81 40orU.S.LaVoieHealthScienceDavid Connolly, +1 617-374-8800, Ext. 108dconnolly@lavoiehealthscience.comorInvestors and analystsNewron PharmaceuticalsStefan Weber, CEO, +39 02 6103 46 30ir@newron.comorU.S.LaVoieHealthScienceKristina Coppola, +1 617-374-8800, Ext. 105kcoppola@lavoiehealthscience.com Help employers find you! Check out all the jobs and post your resume.

Collaborate

100 Deals associated with Sarizotan Hydrochloride

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KEGG	Wiki	ATC	Drug Bank
D05804	Sarizotan Hydrochloride	-	DB06454

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cough	Phase 3	GB	Newron Pharmaceuticals SpA	26 Oct 2016
Cough	Phase 3	IN	Newron Pharmaceuticals SpA	26 Oct 2016
Cough	Phase 3	US	Newron Pharmaceuticals SpA	26 Oct 2016
Cough	Phase 3	IT	Newron Pharmaceuticals SpA	26 Oct 2016
Cough	Phase 3	AU	Newron Pharmaceuticals SpA	26 Oct 2016
Rett Syndrome	Phase 3	AU	Newron Pharmaceuticals SpA	26 Oct 2016
Rett Syndrome	Phase 3	US	Newron Pharmaceuticals SpA	26 Oct 2016
Dyskinesias	Phase 3	US	EMD Serono, Inc.	30 Sep 2004
Parkinson Disease	Phase 3	US	EMD Serono, Inc.	30 Sep 2004
Rett Syndrome	Preclinical	GB	Newron Pharmaceuticals SpA	26 Oct 2016

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02790034 (STARS, CTgov)	Phase 2/3	Cough \| Rett Syndrome	129	Sarizotan low dose (Sarizotan Low Dose)	pyathybksj(qacpujqepc) = fsaljnjlxx rzttteanfc (pkxckggzoz, fttlqbhfud - xcaqkhlbtu) View more	-	21 Dec 2021
				Sarizotan high dose (Sarizotan High Dose)	pyathybksj(qacpujqepc) = jdmykfdytq rzttteanfc (pkxckggzoz, qosdidyxuu - wmmlpqvxpt) View more
NCT00105508 (CTgov)	Phase 3	Dyskinesias \| Parkinson Disease	506	Sarizotan (Sarizotan)	yqytwbekzc(vgvzuguvfp) = sspkouebma ybvpqztyrh (ygqbkpsivh, tnbvzcisxc - cdxgootwpm) View more	-	26 Jul 2018
				Placebo (Placebo)	yqytwbekzc(vgvzuguvfp) = qfntacbymq ybvpqztyrh (ygqbkpsivh, fmkjijbrla - jixsjnilpp) View more
NCT00105521 (CTgov)	Phase 3	Parkinson Disease \| Dyskinesias	398	Placebo (Placebo)	jcqffnqhqh(mcngveworg) = yfcsleebxb gcczdtszzi (gqebhqfbuz, ocxhyyptzy - sdmkodtmav) View more	-	02 Apr 2018
				Sarizotan (Sarizotan 4 mg/Day)	jcqffnqhqh(mcngveworg) = sjirtykhnh gcczdtszzi (gqebhqfbuz, aorzotsuqf - dqsyyxvakr) View more

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