A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of Atuliflapon Given Orally Once Daily for Twelve Weeks in Adults With Moderate to Severe Uncontrolled Asthma

This is a randomised, placebo-controlled, double-blind study to assess the efficacy and safety of Atuliflapon administered once daily over a 12-week treatment period to adult participants with moderate to severe uncontrolled asthma.

Start Date27 Jan 2022

Sponsor / Collaborator

AstraZeneca PLC

NCT04601467

/ TerminatedPhase 2IIT

PASSIvation of Vulnerable Plaque With AZD5718 in AcuTe Coronary syndromE

This is a multi-center study conducted at 8 sites in 2 countries (Singapore, New Zealand). Patients with an acute myocardial infarction (AMI) were randomized in a ratio of 1:1 ratio to receive AZD5718 (Atuliflapon) 125 mg or placebo for 12 months to assess the efficacy of AZD5718 to prevent coronary plaque progression as measured on serial computer tomographic coronary angiography.

Start Date12 Jul 2021

Sponsor / Collaborator

University of Otago

[+1]

NCT04734275

/ CompletedPhase 1

A Randomised, Single-dose, Open-label, Single-centre, Crossover Study to Assess the Relative Bioavailability and Safety of Different Formulations of AZD5718 in Fasted and Fed State in Healthy Volunteers

This study will be a randomised, open-label, 3-period, 3-treatment, single-dose, crossover study in healthy subjects The study will be performed at a single study centre in the United Kingdom.

Start Date01 Feb 2021

Sponsor / Collaborator

AstraZeneca PLC

[+1]

100 Clinical Results associated with Atuliflapon

100 Translational Medicine associated with Atuliflapon

100 Patents (Medical) associated with Atuliflapon

Literatures (Medical) associated with Atuliflapon

01 Nov 2024·Journal of Computational Biophysics and Chemistry

Molecular Docking, Quantum Mechanics and Molecular Dynamics Simulation of Anti-CAD Drugs Against High-Risk Xanthine Dehydrogenase Variants Associated with Oxidative Stress Pathways

Author: Ahmed, Shiek S. S. J. ; Sudhan, M. ; Emran, Talha Bin ; Attia, Sabry M. ; Ahmad, Sheikh F. ; Janakiraman, V.

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the con served regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from −7.95 kcal/mol to −10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, −5.73 kcal/mol to −8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

01 Oct 2024·Pharmacology Research & Perspectives

Disposition of orally administered atuliflapon, a novel 5‐lipoxygenase‐activating protein inhibitor in healthy participants

Article

Author: Nelander, Karin ; Heijer, Maria ; Gränfors, Malin ; Sidhu, Sharan ; Li, Xue‐Qing ; Samuelsson, Kristin ; Ericsson, Hans ; Amilon, Carl ; Lindstedt, Eva‐Lotte ; Lindmark, Bo ; Garkaviy, Pavlo ; Weidolf, Lars ; Knöchel, Jane ; Bragg, Ryan A.

Abstract:

In this study, the mass balance, pharmacokinetics (PK) and metabolism of atuliflapon, a novel 5‐lipoxygenase‐activating protein inhibitor, were investigated in healthy male subjects. A single oral dose of 200 mg [14C]atuliflapon suspension was administered to six healthy male subjects. Mass balance, PK and metabolite profiles of atuliflapon were analyzed using radioactivity monitoring and liquid chromatography with mass spectrometry analysis. The safety of atuliflapon was assessed during the study. Atuliflapon was rapidly absorbed with a median tmax of 1.5 h, followed by a biphasic decline in plasma exposure rendering a terminal half‐life of ~20 h. Unchanged atuliflapon was the predominant radioactive component in plasma, accounting for 40.1% of the total drug‐related exposure (DRE), while a direct N‐glucuronide was the only metabolite exceeding 10% of DRE, accounting for 20.9%. Renal excretion of intact atuliflapon accounted for <1% of the administered dose. In total 85.2% of administered radioactivity was recovered over 312 h with 79.3% and 5.9% in feces and urine, respectively. Parent atuliflapon contributed to approximately 40% of the recovered dose in excreta, while metabolites resulting from phase 1 oxidative pathways accounted for more than 30% of the excreted dose. Overall, a single oral dose of 200 mg [14C]atuliflapon suspension was well tolerated in healthy male subjects. The human metabolism and disposition data obtained will support future development and submissions of atuliflapon as a potential candidate drug for the treatment of cardiovascular, cardiorenal, and respiratory indications.

01 Sep 2024·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

A drug–drug interaction study and physiologically based pharmacokinetic modelling to assess the effect of an oral 5‐lipoxygenase activating protein inhibitor on the pharmacokinetics of oral midazolam

Article

Author: Kat Connolly ; Hodan Ali ; Eva‐Lotte Lindstedt ; Iain MacPhee ; Hans Ericsson ; Maria Heijer ; Jane Knöchel ; Helena Ödesjö ; Karin Nelander ; Pablo Forte ; Vijender Panduga ; Malin Aurell

Aims:

Early clinical studies have indicated that the pharmacokinetics of Atuliflapon (AZD5718) are time and dose dependent. The reason(s) for these findings is(are) not fully understood, but pre‐clinical profiling suggests that time‐dependent CYP3A4 inhibition cannot be excluded. In clinical practice, Atuliflapon will be co‐administered with CYP3A4 substrates; thus, it is important to determine the impact of Atuliflapon on the pharmacokinetics (PK) of CYP3A4 substrates. The aim of this study was to evaluate the effect of Atuliflapon on the pharmacokinetics of a sensitive CYP3A4 substrate, midazolam, and to explore if the time‐/dose‐dependent effect seen after repeated dosing could be an effect of change in CYP3A4 activity.

Methods:

Open‐label, fixed‐sequence study in healthy volunteers to assess the PK of midazolam alone and in combination with Atuliflapon. Fourteen healthy male subjects received single oral dose of midazolam 2 mg on days 1 and 7 and single oral doses of Atuliflapon (125 mg) from days 2 to 7. A physiologically based pharmacokinetic (PBPK) model was developed to assess this drug–drug interaction.

Results:

Mean midazolam values of maximum plasma concentration (Cmax) and area under the curve (AUC) to infinity were increased by 39% and 56%, respectively, when co‐administered with Atuliflapon vs. midazolam alone. The PBPK model predicted a 27% and 44% increase in AUC and a 23% and 35% increase in Cmax of midazolam following its co‐administrations with two predicted therapeutically relevant doses of Atuliflapon.

Conclusions:

Atuliflapon is a weak inhibitor of CYP3A4; this was confirmed by the validated PBPK model. This weak inhibition is predicted to have a minor PK effect on CYP3A4 metabolized drugs.

News (Medical) associated with Atuliflapon

30 Apr 2026

·www.biospace.com

AstraZeneca prunes asthma, rare disease pipeline, cultivates cancer portfolio

iStock, Ekaterina Chergik While AstraZeneca has discontinued work on four assets—including one in asthma and another in acromegaly—the pharma has also elected to take forward a bispecific antibody that destroys the EGFR protein. AstraZeneca is using the first-quarter earnings season as an opportunity to reshape its pipeline, electing to end the development of an investigational therapy for asthma while also taking on a bispecific antibody for cancer. AstraZeneca will no longer be putting money behind atuliflapon, an oral inhibitor of the FLAP protein that was in a Phase 2 study for patients with moderate to severe asthma. The decision to abandon atuliflapon was “due to efficacy,” according to a company presentation on Wednesday released alongside AstraZeneca’s Q1 earnings report. Had the asset not been scrapped, the mid-stage study of atuliflapon was scheduled to complete in July . Alongside atuliflapon, AstraZeneca also discontinued three other programs: one for advanced clear cell renal cell carcinoma, a second for dyslipidemia and the last for acromegaly. All three cuts were driven by “strategic portfolio prioritization,” according to the pharma’s company presentation. As AstraZeneca makes cuts to certain parts of its pipeline, it grows elsewhere. Also on Wednesday, the company exercised its license option with Pinetree Therapeutics, gaining the exclusive global rights to advance and market a potentially first-in-class anti-EGFR bispecific antibody. The asset, dubbed PTX-299, is designed to avert treatment resistance that arises with other EGFR-targeting therapies. The molecule doesn’t merely block EGFR activity—a key driver of cancer—but also elicits the selective destruction of these proteins. This targeted degradation mechanism could potentially overcome resistance pathways, Pinetree said in its news release. Wednesday’s license option triggers a $25 million milestone payment to Pinetree. The companies first partnered in July 2024 for $45 million upfront and the potential of up to $500 million in milestones. Pinetree is also entitled to tiered royalties on net global sales. By exercising the license option, AstraZeneca will now assume full responsibility for all R&D, regulatory and commercialization activities for PTX-299. It is currently unclear what specific cancer types the pharma aims to address. Earnings AstraZeneca bullish on $80B sales goal after beating expectations, Phase 3 data wins After a quarter in which sales topped $15 billion and key readouts went AstraZeneca’s way, the company is increasingly confident that its 2030 revenue target is in reach. April 29, 2026 · 2 min read · Nick Paul Taylor Read more AstraZeneca also reported Q1 earnings results on Wednesday, touting sales of $15.3 billion —cleanly surpassing the $14.6 consensus estimate. The pharma’s 8% year-on-year growth was driven largely by its cancer and rare disease businesses, which surged 16% and 15%, respectively. On the R&D front, AstraZeneca likewise secured key wins during the quarter, including for chronic obstructive pulmonary disease drug tozorakimab and hypophosphatasia hopeful efzimfotase alfa. Taken together, the encouraging clinical and commercial Q1 performance has helped build AstraZeneca’s confidence in meeting its 2030 revenue target of $80 billion.

License out/inPhase 2Phase 3Clinical ResultFinancial Statement

29 Apr 2026

·www.fiercebiotech.com

AstraZeneca scraps FLAP inhibitor after flunking phase 2 asthma trial

As well as dumping atuliflapon, AstraZeneca also disclosed it had ended work on three other programs.\n AstraZeneca has scrapped an asthma program after the FLAP inhibitor flopped in a phase 2 trial.The U.K.-based Big Pharma had been evaluating the therapy, called atuliflapon, in a midstage study of 666 patients with moderate-to-severe uncontrolled asthma. The trial kicked off in 2022, according to the federal trials database, with the aim of demonstrating that atuliflapon could slow the occurrence of the first serious asthma exacerbation when compared to placebo over 12 weeks.However, AstraZeneca disclosed in its first-quarter earnings documents (PDF) that the company has discontinued the trial “due to efficacy.” Atuliflapon has also been removed from the pharma’s pipeline entirely.The 5-lipoxygenase activating protein (FLAP) is an important component in the leukotriene pathway, the signaling process that controls inflammation and immunity. However, no FLAP inhibitors have yet made it to market.GSK licensed FLAP inhibitors from Amiris Pharmaceuticals back in 2008. The Big Pharma took one of these therapies, renamed fiboflapon, as far as a phase 2 asthma study before halting the trial early. As well as dumping atuliflapon, AstraZeneca also disclosed this morning that it had ended work on three other programs, blaming each decision on a “strategic portfolio prioritization.”They included ALXN2420, a GH receptor antagonist that the pharma had been evaluating in a phase 2 study of 60 patients with pituitary gland disorder acromegaly. It marks the latest drug to be scrapped from AstraZeneca’s rare disease unit since the company bought Alexion back in 2020.Meanwhile, AstraZeneca revealed it has ended work on AZD1705, an ANGPTL3 inhibitor that was being evaluated in a phase 1 study of 112 patients with dyslipidemia. The other phase 1 asset thrown on the scrap heap was AZD6912, a siRNA drug being tested in 40 healthy volunteers that was being lined up as a potential treatment for rheumatoid arthritis.AstraZeneca has other siRNA drugs still in the works, such as ALXN2030, an siRNA targeting the C3 complement protein, which has entered a phase 2 study in kidney transplant patients experiencing antibodies attacking their new organ.

Phase 2Phase 1

29 Apr 2026

·endpoints.news

AstraZeneca cuts a couple of late-stage life-cycle trials after disappointing efficacy

AstraZeneca said it had stopped several mid- and late-stage trials of some of its pipeline programs in the past few months, potentially limiting some of the life-cycle extensions it was hoping for. Its first-quarter presentation shows it has canned a Phase 3 trial called ARTEMIS, assessing the complement inhibitor Ultomiris in acute kidney injury associated with cardiac surgery. The company said the trial showed no evidence of efficacy at an interim analysis. There were no new safety concerns, and AstraZeneca will continue to assess Ultomiris in other uses. AstraZeneca also shut down a late-stage renal cell carcinoma (RCC) trial of Imfinzi plus the MET inhibitor Orpathys, which it licensed from China’s Hutchmed. The trial missed its primary endpoint of progression-free survival versus Pfizer’s Sutent, which has been on sale for RCC for 20 years. A Phase 3 trial of Breztri in the lung disease COPD met its primary endpoint by showing improved inhaling capacity during exercise versus placebo. But AstraZeneca disclosed that the trial missed statistical significance on its second primary objective, which assessed the drug versus dual therapy with an inhaled steroid and a long-acting beta-2 agonist on measures of hyperinflation. Also, the company abandoned development of the growth hormone receptor antagonist ALXN2420, which was in a Phase 2 study for acromegaly, for strategic reasons. ALXN2420 was originally developed by the Japanese company PeptiDream and licensed to Amolyt Pharma before Amolyt’s acquisition by AstraZeneca. AstraZeneca also ended development of atuliflapon, a FLAP inhibitor, for efficacy reasons. It was in a mid-stage trial in asthma. Several other key readouts were delayed. Data from two trials of AstraZeneca’s TROP2-directed ADC Datroway in non-small cell lung cancer will now come next year, Jefferies analysts wrote in a same-day note. They added that the trial was tweaked to include biomarker measurements, and this contributed to the delayed results. Phase 3 data on the transthyretin depleter cliramitug in transthyretin amyloid cardiomyopathy are also now expected in 2027 at the earliest. AstraZeneca licensed the drug from Neurimmune in 2022. Overall, however, AstraZeneca had a good quarter. Its revenue and core operating profit increased to $15.3 billion and $5.4 billion, respectively, as sales of its kidney and heart drug Farxiga and other products including Ultomiris came in higher than Wall Street had expected.

Phase 3Phase 2AcquisitionDrug ApprovalClinical Trial Termination

100 Deals associated with Atuliflapon

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	United States	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Japan	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Argentina	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Australia	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Bulgaria	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Chile	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Croatia	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Germany	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Hungary	AstraZeneca PLC	27 Jan 2022
Asthma	Phase 2	Netherlands	AstraZeneca PLC	27 Jan 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04492722 (CTgov)	Phase 2	Chronic Kidney Diseases	613	AZD5718+Dapagliflozin 10 mg (AZD5718 Dose 1 + Dapagliflozin 10 mg)	ejhkrfffdw(mawyqfvbbp) = myydmdrlzl sfbsmtuinv (pxvtxbzgqv, xgyjejzhad - bhzbwsvlhn) View more	-	26 Dec 2023
NCT04492722 (CTgov)	Phase 2	Chronic Kidney Diseases	613	AZD5718+Dapagliflozin 10 mg (AZD5718 Dose 2 + Dapagliflozin 10 mg)	ejhkrfffdw(mawyqfvbbp) = fbwjhwoyry sfbsmtuinv (pxvtxbzgqv, rdmjpaufak - ghabvqurid) View more	-	26 Dec 2023
NCT03317002 (FLAVOUR, CTgov)	Phase 2	Coronary Artery Disease	129	Placebo	qunmeplkok(tioexdcfkc) = csphbotiwl gzzmhmdnul (uolrrcekon, 44.38) View more	-	30 Jun 2021

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