This study, HALO-DMD-03, is a follow-on study to HALO-DMD-01 and HALO-DMD-02, and allows continued open-label access to HT-100 for subjects who have completed these studies. HALO-DMD-03 will provide safety and strength and function data on continuous long-term dosing. Data from this study will be used to inform the safety, tolerability, and dose selection for a future trial of HT-100 in boys with Duchenne Muscular Dystrophy (DMD).

Start Date01 May 2015

Sponsor / Collaborator

Akashi Therapeutics Inc

NCT01978366

/ TerminatedPhase 2

An Open Label Extension Study of HT-100 in Patients With Duchenne Muscular Dystrophy Who Have Completed Protocol HALO-DMD-01

This study is designed to provide 6-months continuous dosing with the study medication, called HT-100, on participants who successfully completed the predecessor study (HALO-DMD-01). The main purpose of this study is to assess chronic safety, tolerability, pharmacodynamic activity (testing the drug's effect on DMD) and population pharmacokinetics (measuring how much drug is in the bloodstream) in participants with a broad spectrum of Duchenne muscular dystrophy (DMD).

Start Date01 Oct 2013

Sponsor / Collaborator

Processa Pharmaceuticals, Inc.

NCT01847573

/ TerminatedPhase 1/2

A Phase 1b Open Label, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-100 in Patients With Duchenne Muscular Dystrophy

The main purpose of this study is to test the safety and tolerability of different, increasing doses of an experimental medication called HT-100 in boys and young men with Duchenne muscular dystrophy (DMD). The study medication, HT-100, is a medicine that may help promote healthy muscle regeneration, diminish inflammation and the resulting damage to muscle, and decrease the scar tissue that forms in the muscles of children with DMD. In this study, pharmacokinetic sampling, or measurements of the amount of HT-100 in the bloodstream will also be taken.

Start Date01 May 2013

Sponsor / Collaborator

Processa Pharmaceuticals, Inc.

100 Clinical Results associated with Halofuginone Hydrobromide

100 Translational Medicine associated with Halofuginone Hydrobromide

100 Patents (Medical) associated with Halofuginone Hydrobromide

620

Literatures (Medical) associated with Halofuginone Hydrobromide

01 Feb 2025·EUROPEAN JOURNAL OF PHARMACOLOGY

Experimental study on the inhibitory effect of Halofuginone on NSCLC

Article

Author: Li, Shanshan ; Fan, Fangtian ; Liu, Shiyao ; Liu, Hao ; Liu, Peipei ; Zhang, Mengxiao ; Han, Yuehua ; Li, Yongping ; Zhu, Juan ; Meng, Zixuan

In recent decades, significant advancements have been achieved in non-small cell lung cancer (NSCLC) treatment. However, drug resistance, postoperative recurrence, distant metastasis, and other critical issues arise during NSCLC treatment. Natural products play a crucial role in the development of anti-tumor drugs. Halofuginone (HF) is a derivative of Febrifugine, an extract of Dichroa febrifuga Lour, a traditional Chinese medicine. Recent studies on HF have demonstrated its antitumor activity and great potential for clinical applications. However, its antitumor effects and mechanisms in NSCLC remain unknown. This study aimed to elucidate the antitumor effect of HF on NSCLC and preliminarily explore its mechanism of action. The proliferation-related assay revealed that HF could inhibit the proliferation of lung adenocarcinoma cells HCC827 and H1975. Network pharmacology of HF and NSCLC indicated that HF could induce cellular oxidative stress, and the antitumor effect was related to autophagy, apoptosis, and cell cycle arrest. Experimental analysis using flow cytometry and western blotting confirmed that HF indeed induced autophagy, enhanced apoptosis, and caused cell cycle arrest. The addition of N-acetyl-cysteamine acid inhibits the HF-induced increase in reactive oxygen species levels, inhibits autophagy and apoptosis, and alters cell cycle distribution. The HCC827 transplantation tumor animal model established that HF substantially inhibited the growth of transplanted tumors. These findings suggest that HF exerts a significant inhibitory effect on NSCLC in vivo and in vitro. The inhibitory effect of HF on NSCLC was associated with the increase of ROS in tumor cells, induction of autophagy and apoptosis, and cell cycle arrest.

01 Jan 2025·MICROBIAL PATHOGENESIS

Gene silencing of Histidyl-tRNA synthetase in Leishmania donovani promastigotes inhibits parasite growth and reduces virulence: A comprehensive computational and in vitro study

Article

Author: Kushwaha, Vikas ; Capalash, Neena ; Saini, Sandeep

The majority of anti-leishmanial drugs used for treating trypanosomatid parasites help to reduce human morbidity and mortality. However, parasites have developed drug resistance, which has made it challenging to treat leishmaniasis. Therefore, new drugs and drug targets need to be identified. Protein synthesis is a crucial anabolic mechanism necessary for parasite survival. Histidyl-tRNA synthetase (HisRS) is an essential enzyme that is required for histidine incorporation into proteins. Recent studies on HisRS have shown differences between trypanosomatid HisRS and human HisRS, which could lead to the development of trypanosomatid HisRS structure-based inhibitors. This study aims to determine the role of L. donovani HisRS (LdHisRS) in parasite growth and virulence in vitro using RNAi. The silencing effect of LdHisRS expression was determined using qPCR. The results showed that after 24 and 48 h of incubation with 90 ng siRNAs, LdHisRS mRNA expression levels were significantly reduced by ∼3.14-fold and ∼3.90-fold, respectively. SiRNA-treated parasites also exhibited ∼46.6 % delayed growth and ∼47 % reduced virulence. Additionally, homology modeling, virtual screening, and molecular docking studies were performed with potential inhibitors that have significant suppressive activity in bacteria, fungi, and viruses. Halofuginone was found to have the best binding affinity of -9.09 kcal/mol as a potent inhibitor against LdHisRS. The molecular dynamics (MD) results showed that halofuginone could interact with the various active site segments, potentially blocking substrate access. The data on gene silencing through siRNA suggests that LdHisRS is essential for the parasite's growth and survival. The computational findings could lead to the development of a potent ligand (halofuginone) as a future anti-leishmanial drug, paving the way for an effective therapeutic treatment.

01 Dec 2024·JOURNAL OF MOLECULAR HISTOLOGY

Halofuginone ameliorates the susceptibility to atrial fibrillation by activating the PI3K/Akt signaling pathway

Article

Author: Shen, Chunjian ; Zhao, Xiaolong ; Zhang, Jing ; Xu, Feng

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Halofuginone (HF) exerts beneficial effects on organ fibrosis, periodontitis, and cancer. However, the effect of HF against AF remains unknown. During the induction of AF, the rats were intragastrically administered HF (5 mg/kg and 10 mg/kg) daily for 7 consecutive days. Cardiac function was evaluated through echocardiographic analysis. The presence of pathological changes and interstitial fibrosis in the left atrial tissues were investigated. Intracellular Ca²⁺ homeostasis and mitochondrial function in atrial tissues were evaluated. The activation of the PI3K/Akt signaling pathway was examined, and an allosteric Akt inhibitor, MK-2206, was applied to confirm the involvement of the PI3K/Akt signaling pathway in the protection against AF by HF. The administration of HF resulted in a prolongation of the atrial effective refractory period (AERP), a reduction in both the duration and inducibility of AF, and a decrease in atrial weight, heart weight, atrial weight/body weight ratio, and heart weight/body weight ratio in rats with AF. In addition, the administration of HF resulted in a reduction in left atrial diameter (LAD) and an increase in left ventricular internal diameter diastolic (LVIDd), ejection fraction (EF), and fractional shortening (FS), while having no effect on left ventricular internal diameter systolic (LVIDs). The pathological changes and cardiac fibrosis observed in rats with AF were mitigated by HF. Moreover, HF enhanced mitochondrial function, suppressed cardiomyocyte apoptosis, and activated the PI3K/Akt pathway in AF rats. Furthermore, the protective effect against AF was also observed in an in vitro model. The effects of HF on fibrosis markers, intracellular Ca²⁺ homeostasis, mitochondrial function, and cardiac apoptosis were blocked by MK-2206. HF alleviated the susceptibility to AF in vivo and in vitro via the activation of the PI3K/Akt signaling pathway.

News (Medical) associated with Halofuginone Hydrobromide

25 Jan 2016

·www.akashirx.com

Dosing and Enrollment in HT-100 Trial Suspended

Dosing and Enrollment in HT-100 Trial Suspended: Updated February 4 Dosing and new patient enrollment in all cohorts of the HALO trial, a study evaluating the compound HT-100 in patients with Duchenne muscular dystrophy, a rare disease that results in muscle degeneration and premature death, are being suspended. We are saddened to report that one of the patients in the trial, receiving 60μg/kg/d (the highest dose in the study), is experiencing serious, life-threatening health issues, and the company is working with the FDA to analyze the situation. We do not yet know to what extent the patient’s health issues are related to HT-100 and/or to other factors. Updated February 4: It is with great sorrow that we share that the brave young man who was experiencing serious, life-threatening health issues has passed away. We offer our deepest condolences to his family and loved ones. Akashi has initiated a comprehensive investigation, beginning with detailed data reviews and in vitro studies, to evaluate the extent to which the patient’s health issues are related to HT-100 and/or to other factors. We will share updates as we reach conclusions in the investigation. What steps is Akashi taking to analyze the situation? Updated February 4: Akashi has initiated a comprehensive investigation, which includes a careful review of all patient records, with a particular focus on this young man’s record, and is initiating the first in a series of studies to further analyze what happened. Experts from outside the company are helping Akashi’s scientists and clinicians in these efforts. We continue to work with the FDA, and based on what we find, our research program will determine additional protective measures, if any, that should be included in the HT-100 program. Have health issues of this kind previously been reported in the HALO trial? None of the other patients in the clinical program have experienced a health issue of this kind or of this severity. To date, patients in the three lower-dose cohorts have been treated for between 11 and 19 months with HT-100, amounting to more than 20 patient-years of favorable data, with no other serious events related to study drug, while this patient had been receiving HT-100 at higher doses for approximately two weeks. An interim safety and efficacy analysis of HALO released in June of 2015 showed promising results for boys and young men enrolled in the HT-100 trial at lower doses, including data supporting improvement in muscle strength, with no serious adverse events related to the study drug. Why has Akashi suspended the trial? The trial has been suspended, based on discussions with the FDA, to allow us time to better understand the circumstances that led to this patient’s experiences. We will continue discussions with the FDA and will provide information once the investigation is complete. Our earlier-stage clinical and preclinical programs in Duchenne muscular dystrophy, with experimental compounds DT-200 and AT-300, are not affected. When will the trial be restarted? Our intention is to restart the trial once our investigation into the causes of this patient’s experiences is complete, and Akashi and the FDA are satisfied that any measures that might be necessary can be put in place to address these causes. As we are at the very beginning of the investigation, we cannot provide a projected timeline. As always, our first priority is patient safety. What should patients enrolled in the trial, or planning to enroll in the trial, know? If families of patients participating or planning to participate in the HT-100 trial have any questions, they may contact Akashi at trialinfo@akashirx.com or the principal investigator at their clinical site.

Clinical Study

08 Jan 2016

·www.akashirx.com

Akashi Therapeutics Establishes International Partnership with Grünenthal Group on HT-100 for DMD

Akashi Therapeutics Establishes International Partnership with Grünenthal Group on HT-100 for DMD – Companies to collaborate on advancement of a novel small-molecule therapeutic for Duchenne muscular dystrophy – CAMBRIDGE, Mass. and Aachen, Germany, January 8, 2016 – Akashi Therapeutics, Inc. a clinical stage biopharmaceutical company developing treatments for Duchenne muscular dystrophy (DMD), today announces a $100 million partnership with Grünenthal Group for a global drug development program for the investigational therapeutic HT-100, an orally available small molecule drug candidate in Phase 1b/2a for the reduction of fibrosis and inflammation, and promotion of healthy muscle fiber regeneration in DMD. HT-100 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). “This agreement represents a critical turning point for the company and offers powerful new hope for DMD patients and their families,” said Marc Blaustein, CEO of Akashi Therapeutics, a company that to date has been funded entirely by DMD patient foundations. “We are thrilled to find a partner who shares our commitment to this patient community, and look forward to accessing Grünenthal’s world-class scientific, clinical, regulatory and commercial capabilities to accelerate development and broad global availability of HT-100.” Under the terms of the agreement, Grünenthal will make upfront and milestone payments to Akashi. In addition, the company will assume all post-Phase 2 global development costs through commercialization of an approved product. Grünenthal gains commercialization rights in Europe and Latin America, while Akashi retains rights for the U.S. and other markets. Akashi will receive royalties on net sales. In total, Grünenthal plans to commit more than $100 million to the partnership and will receive royalties on U.S. net sales in exchange for funding development of Akashi’s U.S. commercial infrastructure. “We are very excited about this unique collaboration with Akashi. At Grünenthal, we are highly committed to innovation and have been focusing on bringing innovative therapies to patients with high medical need. We are very motivated to use all our strength for the development of HT-100 together with our partners from Akashi and the patient groups supporting them,” said Dr. Klaus-Dieter Langner, Chief Scientific Officer of Grünenthal. The agreement also lays the groundwork to expand the collaboration to include Akashi’s other pipeline compounds for DMD and to explore additional indications for HT-100, which may also have activity in other fibrotic diseases such as scleroderma and idiopathic pulmonary fibrosis. About HT-100 HT-100 (delayed-release halofuginone) is an orally available, small molecule drug candidate designed to reduce fibrosis and inflammation and promote healthy muscle fiber regeneration in DMD patients. HT-100 has been granted orphan designation for DMD in both the U.S. and E.U., and fast track designation in the U.S. A phase 1b/2a clinical program is currently underway at five hospitals in the U.S. For more information, please contact Akashi Therapeutics (www.akashirx.com). HT-100 development is generously supported by patient advocacy organizations. A list of these organizations can be found at https://akashirx.com/financial-supporters/. About Duchenne Muscular Dystrophy (DMD) Duchenne muscular dystrophy (DMD) is an X-linked recessive, inheritable disease that affects approximately 1 in 3,600 boys. DMD results in muscle degeneration and premature death. Symptoms usually become visible in early childhood: progressive proximal muscle weakness of the legs and pelvis associated with loss of muscle mass is observed first, and this weakness spreads to other parts of the body. As the disease progresses, muscle tissue is replaced by fat and fibrotic tissue (fibrosis). Untreated, most patients are wheelchair dependent by age 10. Due to progressive deterioration of muscle, patients lose ambulation, then arm function, and ultimately experience respiratory and/or cardiac failure. While life expectancy varies, patients typically survive until late in the second or the third decade. About Akashi Therapeutics Akashi Therapeutics is a clinical stage biopharmaceutical company whose mission is to develop treatments for Duchenne muscular dystrophy. Akashi was founded by leading patient organizations Charley’s Fund and Nash Avery Foundation in collaboration with biotechnology industry veterans to impact a central problem in rare diseases: rapid therapy development. Akashi is developing a pipeline of therapies with the goal of transforming Duchenne from a 100% fatal, aggressive muscle-wasting disease to a chronic, manageable condition. For more information, please visit www.akashirx.com. About Grünenthal The Grünenthal Group is an independent, family-owned, international research-based pharmaceutical group headquartered in Aachen, Germany. Grünenthal is an entrepreneurial specialist delivering true benefits to patients. By sustainably investing in research and development above the industrial average, Grünenthal is committing to innovation in order to treat unmet medical needs and bring value-adding products to markets. Grünenthal GmbH is a fully integrated research & development company with a long track record of bringing innovative pain treatments and state-of-the-art technologies to patients. Altogether, the Grünenthal Group is present in 32 countries with affiliates in Europe, Australia, Latin America and the US. Grünenthal products are sold in more than 155 countries and approx. 5,300 employees are working for the Grünenthal Group worldwide. In 2014, Grünenthal achieved revenues of € 1.154 bn. More information: www.grunenthal.com. # # # For more information please contact: Tara DiMilia On behalf of Akashi Therapeutics 908-369-7168 tara.dimilia@tmstrat.com

Orphan DrugLicense out/inFast Track

18 Jun 2015

·www.akashirx.com

Akashi Reports Positive Clinical Data on HT-100

Akashi Therapeutics Reports Positive Clinical Data on HT-100 in Patients with Duchenne Muscular Dystrophy Download as PDF Interim Clinical Data from Ongoing Phase 1b/2a Clinical Program Highlights Statistically Significant Improvements in Muscle Strength Cambridge, Mass. – June 18 , 2015 – Akashi Therapeutics Inc., a clinical stage biopharmaceutical company developing treatments for Duchenne muscular dystrophy (DMD), today announced positive interim clinical data from an ongoing Phase 1b/2a clinical program with HT-100 (delayed-release halofuginone) an orally available, small molecule developed to reduce fibrosis and inflammation and promote healthy muscle fiber regeneration in boys with DMD. In the clinical program, statistically significant differences in muscle strength as compared to a matched external control cohort and a favorable safety profile were observed. “We are excited by these interim Phase 1b/2a clinical data for HT-100, a powerful anti-inflammatory and anti-fibrotic, which further demonstrate its potential in the treatment of DMD,” said Marc B. Blaustein, CEO of Akashi Therapeutics. “As a group, the boys in this study showed an increase in muscle strength over their baseline and a statistically significant increase relative to a comparable external control cohort, and we look forward to further evaluating and reporting on the progress of HT-100 as a promising treatment option for all boys with DMD as the study continues.” Highlights of the interim data as of June 12 include: The 10 DMD patients participating in the trial for 18 to 22 months and with at least six months of continuous dosing achieved mean total muscle strength 22.3% greater than levels predicted by comparable steroid-treated external control (p=0.027) as measured by quantitative muscle testing (QMT) of upper and lower extremity muscle groups. The mean increase in total muscle strength compared to baseline (study entry) over 18-22 months was 11.7%. These efficacy findings are in the trial’s 2 lowest dose cohorts (mean age[SD]=10.4[2.55]). All study participants are on a stable dose of corticosteroids. HT-100 continues to be well-tolerated with no serious adverse events. The safety database in this study reflects a cumulative 10.5 years of dosing, with 6 patients dosed for a total of 12-13 months, and 10 patients dosed continuously for 9-10 months. About HT-100 HT-100 (delayed-release halofuginone) is an orally available, small molecule drug candidate designed to reduce fibrosis and inflammation and promote healthy muscle fiber regeneration in DMD patients. HT-100 has been granted orphan designation for DMD in both the U.S. and E.U., and fast track designation in the U.S. A phase 1b/2a clinical program is currently underway at five hospitals across the U.S. HT-100 development is generously supported by patient advocacy organizations. A list of these organizations can be found at https://akashirx.com/financial-supporters/. About Duchenne muscular dystrophy (DMD) Affecting approximately 1 in 3,600 boys worldwide, DMD is the most common of the muscular dystrophies and the most lethal genetic disorder of childhood. It is caused by a genetic mutation that renders boys unable to make functional dystrophin, a protein critical for normal muscle function. Young men with DMD show progressive signs of physical impairment as early as age three, lose the ability to walk in their teens, and die of cardiac or respiratory failure in their late twenties or early thirties. About Akashi Therapeutics Akashi Therapeutics is a clinical stage biopharmaceutical company whose mission is to develop treatments for Duchenne muscular dystrophy. Akashi was founded by leading patient organizations and biotechnology industry veterans and is managed by a seasoned team of drug development experts to impact a central problem in rare diseases: rapid therapy development. Akashi is developing a pipeline of therapies with the goal of transforming Duchenne from a 100% fatal, aggressive muscle-wasting disease to a chronic, manageable condition. For more information, please visit www.akashirx.com. Akashi Therapeutics Contact: Marc B. Blaustein, CFA info@akashirx.com 617.431.7250 Media Contact: Gina Nugent, The Yates Network gina@theyatesnetwork.com

Clinical ResultFast TrackOrphan Drug

100 Deals associated with Halofuginone Hydrobromide

External Link

KEGG	Wiki	ATC	Drug Bank
D04413	Halofuginone Hydrobromide	-	DB04866

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Muscular Dystrophy, Duchenne	Phase 2	US	Processa Pharmaceuticals, Inc.	01 Oct 2013
Bladder Cancer	Phase 2	IL	Collgard Biopharmaceuticals Ltd.	-
Bladder Cancer	Phase 2	GB	Collgard Biopharmaceuticals Ltd.	-
Neoplasms	Phase 2	BE	-	-
Neoplasms	Phase 2	-	Collgard Biopharmaceuticals Ltd.	-
Neoplasms	Phase 2	NL	-	-
Scleroderma, Systemic	Phase 2	GB	Collgard Biopharmaceuticals Ltd.	-
Coronary Restenosis	Preclinical	US	-	-
Liver Cirrhosis	Preclinical	IL	Collgard Biopharmaceuticals Ltd.	-
Renal fibrosis	Preclinical	IL	Collgard Biopharmaceuticals Ltd.	-

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2022	Not Applicable	-	-	Halofuginone	zkzknhabft(qmesewzqdb) = hnjajwgohc leztbqzarq (wwdtgzzdoy ) View more	-	01 May 2022
				PBS	zkzknhabft(qmesewzqdb) = wmjpirqfhi leztbqzarq (wwdtgzzdoy ) View more
ASTRO2012	Not Applicable	Lung Cancer	-	Halofuginone (Control group)	mxcifromqj(jdubygnaek) = Immunohistochemistry study revealed decrease level of TGF-Î²1 expression in the halofuginone group and the combined group than in any other groups. The TGF-Î²1 level measured with ELISA also showed the similar results kbvuihncfi (oiivubtoch ) View more	-	01 Nov 2012
				Halofuginone group

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