The goal of this clinical trial is to learn about SP-420 ability to remove iron from organs in subjects with transfusion-dependent β-thalassemia. The main questions it aims to answer are:
* How efficient is SP-420 in cleaning iron from the liver?
* How is the safety and tolerability of ascending doses of SP-420?
Participants will:
* Take medication three time weekly
* Attend up to 20 site visits
* Undergo MRI scans

开始日期2023-09-04

申办/合作机构

Pharmacosmos A/S

[+1]

LBCTR2023045220

/ Suspended临床2期

An open-label, dose-escalation, dose-finding, and proof-of-concept trial of SP-420 in subjects with transfusion-dependent ß-thalassemia

开始日期2023-04-24

申办/合作机构

Pharmacosmos A/S

NCT04741542

/ Terminated临床1期IIT

Phase 1, Open-Label, Dose Escalation Study to Assess the Safety of SP-420 in the Treatment of Transfusional Iron Overload

This study enrolls patients with myelodysplastic syndrome (MDS) and myelofibrosis (MFS), with transfusional iron overload and treats them with the investigational iron chelator, SP-420. SP-420 may be better tolerated and safer than commercially available iron chelators. Iron chelation therapy (ICT) has been shown to improve outcomes in iron overload, but adherence is poor due to problems related to ease of administration, tolerability, and safety.

开始日期2021-03-09

申办/合作机构

University of Texas Health Science Center At San Antonio

[+1]

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100 项与 Petadeferitrin 相关的转化医学

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100 项与 Petadeferitrin 相关的专利（医药）

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项与 Petadeferitrin 相关的文献（医药）

2017-12-01·American journal of hematology

Safety and pharmacokinetics of the oral iron chelator SP‐420 in β‐thalassemia

Article

作者: Neufeld, Ellis J. ; Jeglinski, Brenda I. ; Aydinok, Yesim ; Cohen, Alan R. ; Giardina, Patricia J. ; Saliba, Antoine N. ; Viprakasit, Vip ; Kuo, Kevin H. ; Kwiatkowski, Janet L. ; Berk, Gregory ; Pietropaolo, Keith ; Taher, Ali T.

Abstact:

Our phase I, open‐label, multi‐center, dose‐escalation study evaluated the pharmacokinetics (PK) of SP‐420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β‐thalassemia. SP‐420 was administered as a single dose of 1.5 (n = 3), 3 (n = 3), 6 (n = 3), 12 (n = 3), and 24 (n = 6) mg/kg or as a twice‐daily dose of 9 mg/kg (n = 6) over 14‐28 days. There was a near dose‐linear increase in the mean plasma SP‐420 concentrations and in the mean values for Cmax and AUC0‐τ over the dose range evaluated. The median tmax ranged from 0.5 to 2.25 h and was not dose dependent. The study was prematurely terminated by the sponsor due to renal adverse events (AE) including proteinuria, increase in serum creatinine, and one case of Fanconi syndrome. Other adverse effects included hypersensitivity reactions and gastrointestinal disturbances. Based on current dose administration, the renal AE observed outweighed the possible benefits from chelation therapy. However, additional studies assessing efficacy and safety of lower doses or less frequent dosing of SP‐420 over longer durations with close monitoring would be necessary to better explain the findings of our study and characterize the safety of the study drug.

2015-09-01·Bioorganic & medicinal chemistry3区 · 医学

Metabolically programmed iron chelators

3区 · 医学

Article

作者: Wiegand, Jan ; Bergeron, Raymond J ; McManis, James S ; Bharti, Neelam

Extensive structure activity relationship (SAR) studies focused on the desferrithiocin [DFT, (S)-4,5-dihydro-2-(3-hydroxy-2-pyridinyl)-4-methyl-4-thiazolecarboxylic acid] pharmacophore have led to three different DFT analogs being evaluated clinically for the treatment of iron overload diseases, for example, thalassemia. The SAR work revealed that the lipophilicity of a ligand, as determined by its partition between octanol and water, logP(app), could have a profound effect on the drug's iron clearing efficiency (ICE), organ distribution, and toxicity profile. While within a given structural family the more lipophilic a chelator the better the ICE, unfortunately, the more lipophilic ligands are often more toxic. Thus, a balance between lipophilicity, ICE, and toxicity must be achieved. In the current study, we introduce the concept of 'metabolically programmed' iron chelators, that is, highly lipophilic, orally absorbable, effective deferration agents which, once absorbed, are quickly converted to their nontoxic, hydrophilic counterparts.

2012-08-23·Journal of medicinal chemistry1区 · 医学

Substituent Effects on Desferrithiocin and Desferrithiocin Analogue Iron-Clearing and Toxicity Profiles

1区 · 医学

Article

作者: Bergeron, Raymond J. ; McManis, James S. ; Wiegand, Jan ; Bharti, Neelam

Desferrithiocin (DFT, 1) is a very efficient iron chelator when given orally. However, it is severely nephrotoxic. Structure-activity studies with 1 demonstrated that removal of the aromatic nitrogen to provide desazadesferrithiocin (DADFT, 2) and introduction of either a hydroxyl group or a polyether fragment onto the aromatic ring resulted in orally active iron chelators that were much less toxic than 1. The purpose of the current study was to determine if a comparable reduction in renal toxicity could be achieved by performing the same structural manipulations on 1 itself. Accordingly, three DFT analogues were synthesized. The iron-clearing efficiency and ferrokinetics were evaluated in rats and primates; toxicity assessments were carried out in rodents. The resulting DFT ligands demonstrated a reduction in toxicity that was equivalent to that of the DADFT analogues and presented with excellent iron-clearing properties.

项与 Petadeferitrin 相关的新闻（医药）

2021-11-11

·Endpoints

Too much iron? Pharmacosmos is betting $225M on a new potential solution for that

Danish biotech Pharmacosmos has come a long way since it was launched back in 1965 as an active pharmaceutical ingredient (API) manufacturer. While it’s still in the same family, the company now has three drugs approved to treat iron deficiency in humans (and a fourth for piglets). Now, with its latest buyout, the company is looking to add a therapy for just the opposite: iron overload. Pharmacosmos is putting down $225 million to purchase AbFero, a spinout from Raymond Bergeron’s lab at the University of Florida. Its lead candidate, SP-420, recently completed Phase I safety studies as a treatment for transfusional iron overload. While frequent red blood cell transfusions are needed for conditions like ß-thalassemia, sickle-cell disease, and myelofibrosis, a common side effect is iron overload. Red blood cells contain iron, so each time a patient gets a transfusion, they’re adding more iron without any way to get rid of the excess. This extra iron can build up in the internal organs, such as the liver, pancreas or heart, and cause damage over time. To address this problem, doctors prescribe iron chelators — small molecules designed to recognize, bind and remove iron from the body. Novartis has an injectable drug, Desferal, approved, as well as oral options Exjade and Jadenu. But they come with a long list of side effects ranging from impaired vision to kidney problems. SP-420, on the other hand, belongs to a novel class of iron chelators called desferrithiocins — and according to AbFero, it’s designed as a potentially safer alternative with greater efficacy than the currently available drugs. “The role of iron in disease has been vastly underappreciated,” AbFero CEO and co-founder Thomas Neenan said in a statement. “As a leader in iron metabolism disorders, Pharmacosmos is uniquely positioned to realize the full potential of our chelation platform.” Lars Christensen, the youngest son of Pharmacosmos founder Henry Christensen, called the acquisition a “perfect strategic fit,” adding that the company plans on completing the development of SP-420 in transfusional iron overload in addition to exploring other iron-mediated conditions.

小分子药物并购

2021-02-17

·BioSpace

AbFero Pharmaceuticals Announces Funding From Cure Parkinson's For Lead Compound SP-420

HARWELL, England, Feb. 17, 2021 /PRNewswire/ -- AbFero Ltd., a subsidiary of AbFero Pharmaceuticals, Inc., a privately-held clinical stage pharmaceutical company dedicated to treating diseases of iron overload, today announced the award of a grant from Cure Parkinson's for the development of their lead, brain-penetrant iron chelating agent, SP-420, as a disease modifying therapy for Parkinson's disease (PD). The funding will be used to develop biomarkers to demonstrate that SP-420 is an effective targeted therapy for Parkinson's. This is the second grant AbFero has received to support development of SP-420 for the condition, following recent funding from Eureka EUROSTARS. "The role of iron in neurodegenerative diseases grows more compelling every day. Cure Parkinson's has been a strong proponent of iron chelation for Parkinson's, so this grant is particularly meaningful. It further accelerates AbFero's drive towards our first clinical study in Parkinson's," said AbFero CEO Thomas Neenan. Removal of excess brain iron via chelation has long been considered an attractive disease modifying approach, but a therapy with sufficient safety and proven efficacy remains lacking. AbFero expects SP-420 will limit iron accumulation in the brain, reducing iron-related oxidative stress, iron related neuronal death (i.e., ferroptosis), and alpha-synuclein aggregation, well-known neuropathological hallmarks of Parkinson's. Dr Richard Wyse, Director of Research & Development at Cure Parkinson's said: "Iron chelation is an extremely promising line of investigation in Parkinson's. Our funding for this project adds new impetus and expands our long-standing interest in the future relevance of this approach in slowing or stopping long-term neurodegeneration in patients with Parkinson's disease." The grant will fund ongoing development of the small molecule in the laboratory of Professor David Devos, MD, PhD, University of Lille, CHU of Lille, INSERM. "We believe SP-420 is one of the greatest iron chelators, given it has excellent kinetics, high oral bioavailability and biodistribution, and no evidence to date of inappropriate competition with the native iron transport and storage mechanisms of the body," Dr. Devos notes. "AbFero is working urgently to develop best-in-class, next generation iron chelators that will slow progression and improve the quality of life for the nearly 10 million people living with Parkinson's today," Neenan adds. "We're grateful to Cure Parkinson's for their support as we press forward." About AbFero, Ltd. AbFero, Ltd., is a subsidiary of AbFero Pharmaceuticals, Inc., a privately-held clinical stage pharmaceutical dedicated to treating diseases of iron overload. AbFero's technology is based upon the discoveries of a pioneer in the field of iron chelator medicinal chemistry, Professor Raymond Bergeron, University of Florida. Our therapeutic platform addresses transfusional iron overload (TIO) and iron accumulation associated with retinal and neurologic diseases including age-related macular degeneration (AMD), Parkinson's disease (PD), and traumatic brain injury (TBI). AbFero has completed three clinical trials with the company's lead chelator, SP-420. AbFero Ltd., is located in Harwell, UK. For more information, visit . Investor & Media Contact: Mih-Ho Cha mcha@abfero.com

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
输血依赖性地中海贫血	临床2期	丹麦	Pharmacosmos A/S	2023-09-04
β地中海贫血	临床2期	加拿大	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
β地中海贫血	临床2期	黎巴嫩	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
β地中海贫血	临床2期	泰国	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
β地中海贫血	临床2期	土耳其	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
输血依赖性β地中海贫血	临床2期	加拿大	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
输血依赖性β地中海贫血	临床2期	黎巴嫩	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
输血依赖性β地中海贫血	临床2期	泰国	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
输血依赖性β地中海贫血	临床2期	土耳其	AbFero Pharmaceuticals, Inc.初创企业	2020-08-01
铁过剩	临床2期	美国	Genzyme Corp.	2003-09-30