Delving into the Latest Updates on Fevipiprant with Synapse

The purpose of this study was to assess the pharmacokinetics (PK) of fevipiprant (QAW039) delivered as a chewable tablet (CT) in pediatric asthma subjects aged 6 to < 12 years with asthma. The results of this study will support the identification of a fevipiprant dose for subsequent pediatric efficacy studies aiming to provide an exposure similar to that of the to-be marketed adult/adolescent dose. In addition, the first data on safety and tolerability of fevipiprant in this age group was obtained.

Start Date01 May 2019

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

100 Clinical Results associated with Fevipiprant

Login to view more data

100 Translational Medicine associated with Fevipiprant

Login to view more data

100 Patents (Medical) associated with Fevipiprant

Login to view more data

43

Literatures (Medical) associated with Fevipiprant

01 Feb 2023·Biotechnology and Applied BiochemistryQ4 · ENGINEERING & TECHNOLOGY

Pharmacological evaluation of the effects of enzymatically liberated fish oil on eosinophilic inflammation in animal models

Q4 · ENGINEERING & TECHNOLOGY

Article

Author: Bjerknes, Christian ; Singh, Dave ; Sharma, Deepali ; Framroze, Bomi ; Hermansen, Erland ; Currie, Crawford

AbstractThe inappropriate activation of eosinophils is a well‐recognized driver of various human inflammatory diseases including asthma, chronic rhinitis, and various gastrointestinal diseases, including eosinophilic esophagitis. Steroids, both topical and systemic, remain a cornerstone of treatment and can be highly effective. However, some individuals suffer side effects, unresolved symptoms, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated anti‐inflammatory and antioxidant properties as well the reduction of the activation, migration, and survival of eosinophils. Two animal models of eosinophilic inflammation were used to further assess OmeGo's profile. A house dust mite model of induced asthma showed a significant reduction in eosinophilic lung inflammation compared to the negative control, linoleic acid. The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo. In contrast, cod liver oil had no impact on any measure of inflammation. A guinea pig model of mild intraperitoneal eosinophilia showed a significant reduction in eosinophil activity by OmeGo, assessed by chemotaxis and chemokinesis. Apolipoprotein A‐IV, an endogenous human protein with anti‐inflammatory actions, showed a similar but numerically lower effect. OmeGo therefore combines a consistent antieosinophilic action with the known anti‐inflammatory effects of polyunsaturated fatty acids. Proof‐of‐concept studies in asthma are warranted.

04 May 2022·Drug Development and Industrial Pharmacy

Commercial scale transfer of a twin-screw melt granulation process for high drug load fevipiprant tablets

Article

Author: Häcker, Hans-Georg ; Bautista, Manel ; Stocker, Stephan ; Steib-Lauer, Caroline ; Spickermann, Dirk ; Dhareshwar, Sundeep S. ; Rogue, Vincent ; Hirsch, Stefan ; Vicente Martin, Claudia

OBJECTIVEThis work summarizes select methodology of twin-screw melt granulation (TSMG) and process analytical technology that were used in the successful scaling-up and commercial transfer of high drug load (80.5% w/w) immediate release fevipiprant tablets.SIGNIFICANCEThe unique and compelling learnings from this industry work are (1) insights into Novartis AG's commercial scale transfer using TSMG and (2) rapid, nondestructive NIR methodology as a PAT tool for RTR testing. No prior literature combines these two aspects at the level of detail we present/disclose.METHODSScaling up of TSMG was guided by specific energy values obtained for the 27 mm (pilot scale) and 50 mm (commercial scale) twin-screw extruders (TSE). Proven acceptable ranges (PARs) were confirmed by varying the critical process parameters (CPPs) for granulation (screw speed) and tableting (dwell time and crushing strength) at three process levels (upper, target, and lower). An at-line NIR method was developed and validated for real-time release testing (RTRT).RESULTSThe combination of CPPs were selected to have the same effect on critical quality attributes (CQAs), that is, lower (-) and upper (+) process level challenged tablet aspect/appearance and dissolution, respectively. TSMG was performed using a 50 mm extruder at constant feed rate. Compression of the six final blends (∼300 kg) showed no impact of varied granulation and compression process conditions on both CQAs. A near-infrared spectroscopy method was validated to determine content uniformity, assay, identity, and to predict CQAs on uncoated tablets in preparation for a real RTRT of future batches.

01 May 2022·Cureus

Efficacy and Safety of Fevipiprant in Asthma: A Review and Meta-Analysis

Review

Author: Jahangir, Ahmad ; Sharif, Muhammad Ans ; Sattar, Saud Bin Abdul ; Muhammad, Marwah ; Rafay Khan Niazi, Muhammad ; Jahangir, Abdullah ; Sahra, Syeda ; Anwar, Muhammad Yasir ; Chalhoub, Michel

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value < 0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p<0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p<0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

1

News (Medical) associated with Fevipiprant

22 Oct 2019

·www.bioportfolio.com

Novartis downplays late-stage asthma drug failures

Fevipiprant failed the first pair of late-stage clinical trials in asthma. Novartis CEO Vas Narasimhan called a second pair of studies distinct.

100 Deals associated with Fevipiprant

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
D10631	Fevipiprant	-	DB12011

R&D Status

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Allergic asthma	Phase 3	LU	Novartis AG	-
Asthma	Phase 3	PR	Novartis AG	-
Asthma	Phase 2	PR	Novartis AG	-
Asthma	Phase 2	SE	Novartis AG	-
Asthma	Phase 2	TN	Novartis AG	-
Asthma	Phase 2	TN	Novartis AG	-
Asthma	Phase 1	PR	Novartis AG	-
Allergic asthma	Preclinical	LU	Novartis AG	-
Asthma	Preclinical	SE	Novartis AG	-

Login to view more data

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ERS2015	Not Applicable	Asthma sputum eosinophilia	-	QAW039 225mg BID	wvyeriespu(fgqssxmxlw) = xrujqzctmw amzcxmtcdt (svtahxrbxt ) View more	Positive	01 Sep 2015
NCT02563067 \| NCT02555683 (LUSTER-1 \| LUSTER-2, GlobeNewswire) Manual	Phase 3	Asthma	-	QAW039	(gdieuvagxg) = Fevipiprant was well tolerated with adverse events balanced across treatment groups xwhsoseixy (hsbojoqgqq ) View more	Negative	16 Dec 2019
ERS2019	Not Applicable	-	-	Fevipiprant	gjcstyaqjk(ezyohtzvgq) = efzvgnhfvt kppolrknli (nfokltajqj ) View more	Positive	28 Sep 2019
ERS2018	Not Applicable	eosinophilic asthmatics	-	Fevipiprant	qsiraqxber(wxmdxufjbt) = hwwthkgkkb alaivseipf (wnwkgwaxev )	-	15 Sep 2018
ERS2014	Not Applicable	-	-	QAW039	rhlrmvjafs(petjghsoqo) = vbmrwbahmw nmrrjrfqic (xfxgtrvljp )	-	01 Sep 2014
				QAV680	rhlrmvjafs(petjghsoqo) = wnezfnqqbt nmrrjrfqic (xfxgtrvljp )
NCT01253603 (Pubmed \| Pulm Pharmacol Ther)	Phase 2	Allergic asthma	170	QAW039 (fevipiprant) 500 mg	(qmqnbjbvav): Δ = -0.41 (90% CI, -0.69 to -0.13) View more	Positive	01 Aug 2016
				Placebo
NCT01545726 (Pubmed \| Lancet Respir Med) Manual	Phase 2	Pulmonary Eosinophilia	61	Fevipiprant	cohlrscqcq(jlppaarbzk) = fmzvxozgrd qhqywangiw (qxmixlsrgr )	Positive	01 Sep 2016
				Placebo	cohlrscqcq(jlppaarbzk) = vnaopeocca qhqywangiw (qxmixlsrgr )
ERS2014	Phase 2	Pulmonary Eosinophilia	61	QAW039 225mg BID	(pybhmhxgay) = awzakchgfo foidojsgxq (htsxypmxdd )	Positive	01 Sep 2014
NCT03215758 (ZEAL-1, Pubmed) Manual	Phase 3	Asthma	662	fevipiprant	(ipfcdxjifc) = uulhhaqkfp eeirwykgur (wihxulmptm )	Negative	25 Apr 2021
				Placebo	(ipfcdxjifc) = qljtxqdocp eeirwykgur (wihxulmptm )
ERS2017	Phase 1	-	29	Fevipiprant 900mg	(tnwjrzldjh) = The number of AEs was comparable between treatment groups; tachycardia of moderate severity was seen in 1 subject on fevipiprant 900mg without additional symptoms. This event led to temporary halt of study and repeat of Cohort A after protocol amendment. No AEs were seen in Japanese subjects. No SAEs, deaths, or clinically relevant changes in ECG, laboratory values or vital signs (except tachycardia) occurred. ouvnsrclih (oskwwsatdx ) View more	-	01 Sep 2017
				Fevipiprant 1800mg