Fevipiprant

Fevipiprant
Clinical data
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	Investigational;
Pharmacokinetic data
Bioavailability	Unaffected by food
Metabolism	Hepatic glucuronidation
Elimination half-life	~20 hours
Excretion	Renal (≤30%)
Identifiers
	IUPAC name {2-methyl-1-[4-(methylsulfonyl)-2-(trifluoromethyl)benzyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}acetic acid;
CAS Number	872365-14-5;
PubChem CID	23582412;
ChemSpider	23582412;
UNII	2PEX5N7DQ4;
KEGG	D10631;
CompTox Dashboard (EPA)	DTXSID501336031 ;
ECHA InfoCard	100.243.911
Chemical and physical data
Formula	C19H17F3N2O4S
Molar mass	426.41 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C(C2=C(N1CC3=C(C=C(C=C3)S(=O)(=O)C)C(F)(F)F)N=CC=C2)CC(=O)O;
	InChI InChI=1S/C19H17F3N2O4S/c1-11-15(9-17(25)26)14-4-3-7-23-18(14)24(11)10-12-5-6-13(29(2,27)28)8-16(12)19(20,21)22/h3-8H,9-10H2,1-2H3,(H,25,26); Key:GFPPXZDRVCSVNR-UHFFFAOYSA-N;

Fevipiprant (INN; code name QAW039) is a drug of the piprant class that was being developed by Novartis. It is a selective, orally available antagonist of the prostaglandin D₂ receptor 2 (DP₂ or CRTh2).^[1]^[2]^[3]

By 2016 it had advanced to phase III^[4] clinical trials for the treatment of asthma.^[5] However, in 2019 Novartis announced that it was removing fevipiprant from its development program, given that the medicine has failed in two clinical trials in patients with moderate-to-severe asthma. The firm said that it had hoped fevipiprant would be a billion-dollar-selling asthma drug.^[6]

A 2021 analysis sponsored by Novartis of the two phase III trials of fevipiprant concluded that "The ZEAL studies did not demonstrate significant improvement in lung function or other clinical outcomes. These results suggest that DP2 receptor inhibition with fevipiprant is not effective in the studied patient population".^[7]

References

^ ^a ^b Erpenbeck VJ, Vets E, Gheyle L, Osuntokun W, Larbig M, Neelakantham S, et al. (July 2016). "Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers". Clinical Pharmacology in Drug Development. 5 (4): 306–313. doi:10.1002/cpdd.244. PMC 5071756. PMID 27310331.
^ Sykes DA, Bradley ME, Riddy DM, Willard E, Reilly J, Miah A, et al. (May 2016). "Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy". Molecular Pharmacology. 89 (5): 593–605. doi:10.1124/mol.115.101832. PMID 26916831.
^ Erpenbeck VJ, Popov TA, Miller D, Weinstein SF, Spector S, Magnusson B, et al. (August 2016). "The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma". Pulmonary Pharmacology & Therapeutics. 39: 54–63. doi:10.1016/j.pupt.2016.06.005. PMID 27354118.
^ Clinical trial number NCT02555683 for "A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 when Added to Existing Asthma Therapy in Patients with Uncontrolled Severe Asthma" at ClinicalTrials.gov
^ Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MF, Bacher G, et al. (September 2016). "Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial". The Lancet. Respiratory Medicine. 4 (9): 699–707. doi:10.1016/S2213-2600(16)30179-5. hdl:2381/38430. PMID 27503237.
^ "Novartis drops asthma drug fevipiprant after trial failures". Reuters. 2019-12-16. Retrieved 2023-05-09.
^ Castro M, Kerwin E, Miller D, Pedinoff A, Sher L, Cardenas P, et al. (May 2021). "Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2)". EClinicalMedicine. 35: 100847. doi:10.1016/j.eclinm.2021.100847. PMC 8099656. PMID 33997741.

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[pmid27310331-1] Erpenbeck VJ, Vets E, Gheyle L, Osuntokun W, Larbig M, Neelakantham S, et al. (July 2016). "Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo-Controlled Studies in Healthy Volunteers". Clinical Pharmacology in Drug Development. 5 (4): 306–313. doi:10.1002/cpdd.244. PMC 5071756. PMID 27310331.

[2] Sykes DA, Bradley ME, Riddy DM, Willard E, Reilly J, Miah A, et al. (May 2016). "Fevipiprant (QAW039), a Slowly Dissociating CRTh2 Antagonist with the Potential for Improved Clinical Efficacy". Molecular Pharmacology. 89 (5): 593–605. doi:10.1124/mol.115.101832. PMID 26916831.

[pmid27354118-3] Erpenbeck VJ, Popov TA, Miller D, Weinstein SF, Spector S, Magnusson B, et al. (August 2016). "The oral CRTh2 antagonist QAW039 (fevipiprant): A phase II study in uncontrolled allergic asthma". Pulmonary Pharmacology & Therapeutics. 39: 54–63. doi:10.1016/j.pupt.2016.06.005. PMID 27354118.

[4] Clinical trial number NCT02555683 for "A 52-week, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of QAW039 when Added to Existing Asthma Therapy in Patients with Uncontrolled Severe Asthma" at ClinicalTrials.gov

[5] Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MF, Bacher G, et al. (September 2016). "Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial". The Lancet. Respiratory Medicine. 4 (9): 699–707. doi:10.1016/S2213-2600(16)30179-5. hdl:2381/38430. PMID 27503237.

[6] "Novartis drops asthma drug fevipiprant after trial failures". Reuters. 2019-12-16. Retrieved 2023-05-09.

[7] Castro M, Kerwin E, Miller D, Pedinoff A, Sher L, Cardenas P, et al. (May 2021). "Efficacy and safety of fevipiprant in patients with uncontrolled asthma: Two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2)". EClinicalMedicine. 35: 100847. doi:10.1016/j.eclinm.2021.100847. PMC 8099656. PMID 33997741.

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See also

References