Iptacopan: Difference between revisions
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{{Short description|Chemical compound}} |
{{Short description|Chemical compound}} |
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{{Use dmy dates|date=December 2023}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
{{Infobox drug |
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| image = Iptacopan.svg |
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| width = 200 |
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| pronounce = |
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| tradename = Fabhalta |
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| Drugs.com = {{drugs.com|parent|Fabhalta}} |
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| MedlinePlus = |
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| DailyMedID = Iptacopan |
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| pregnancy_category = |
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| routes_of_administration = |
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| routes_of_administration = [[By mouth]] |
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| tradename = |
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| class = [[Complement factor B]] inhibitor |
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| ATC_prefix = L04 |
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| ATC_suffix = AJ08 |
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<!-- Legal status --> |
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| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled --> |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Fabhalta FDA label" /> |
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| legal_EU = Rx-only |
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| legal_EU_comment = <ref name="Fabhalta EPAR" /> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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| synonyms = LNP023 |
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<!-- Identifiers --> |
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| AAN = |
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| CAS_number = 1644670-37-0 |
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| CAS_supplemental = |
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| PubChem = 90467622 |
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| DrugBank = DB16200 |
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| ChemSpiderID = 75533872 |
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| UNII = 8E05T07Z6W |
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| KEGG = D12251 |
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| KEGG2 = D12252 |
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| ChEBI = |
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| ChEMBL = 4594448 |
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| NIAID_ChemDB = |
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| PDB_ligand = JGQ |
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| synonyms = LNP023 |
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| PubChem = 90467622 |
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| SMILES = O=C(O)C1=CC=C([C@H]2N(CC3=C(OC)C=C(C)C4=C3C=CN4)CC[C@H](OCC)C2)C=C1 |
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| StdInChI = 1S/C25H30N2O4/c1-4-31-19-10-12-27(22(14-19)17-5-7-18(8-6-17)25(28)29)15-21-20-9-11-26-24(20)16(2)13-23(21)30-3/h5-9,11,13,19,22,26H,4,10,12,14-15H2,1-3H3,(H,28,29)/t19-,22-/m0/s1 |
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}} |
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'''Iptacopan''' , sold under the brand name '''Fabhalta''', is a [[medication]] used for the treatment of [[paroxysmal nocturnal hemoglobinuria]].<ref name="Fabhalta FDA label">{{cite web | title=Fabhalta- iptacopan capsule | website=DailyMed | date=5 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a76b5845-6e21-4d3b-ad07-cd8df1b60bee | access-date=10 December 2023 | archive-date=10 December 2023 | archive-url=https://web.archive.org/web/20231210095635/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a76b5845-6e21-4d3b-ad07-cd8df1b60bee | url-status=live }}</ref> It is a [[complement factor B]] inhibitor that was developed by [[Novartis]].<ref name="Fabhalta FDA label" /> It is taken [[by mouth]].<ref name="Fabhalta FDA label" /> |
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'''Iptacopan''' ('''LNP023''') is a drug developed by [[Novartis]] designed to treat [[paroxysmal nocturnal hemoglobinuria]] (PNH), a disease in which the [[innate immune system]] destroys red blood cells. It is the first drug that selectively inhibits ''factor B'', the active component of the [[Complement system|complement]]'s [[C3-convertase|C3]] and [[C5-convertase|C5 convertases]].<ref name=blood_adv>{{cite journal | vauthors = Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES | display-authors = 6 | title = Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study | journal = Blood Advances | volume = 6 | issue = 15 | pages = 4450–4460 | date = August 2022 | pmid = 35561315 | doi = 10.1182/bloodadvances.2022006960 | pmc = 9636331 }}</ref> In contrast to other PNH treatments like [[eculizumab]], iptacopan is a small molecule. |
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Iptacopan was approved by the US [[Food and Drug Administration]] (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023.<ref>{{cite press release |title=Novartis receives FDA approval for Fabhalta (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH |url=https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh |access-date=6 December 2023 |website=Novartis |archive-date=12 December 2023 |archive-url=https://web.archive.org/web/20231212071556/https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh |url-status=live }}</ref><ref>{{cite web | title=Novel Drug Approvals for 2023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=6 December 2023 | url=https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023 | access-date=10 December 2023 | archive-date=21 January 2023 | archive-url=https://web.archive.org/web/20230121035617/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023 | url-status=live }}</ref> The FDA considers it to be a [[first-in-class medication]].<ref>{{cite report | title=New Drug Therapy Approvals 2023 | website=U.S. [[Food and Drug Administration]] (FDA) | date=January 2024 | url=https://www.fda.gov/media/175253/download | format=PDF | access-date=9 January 2024 | archive-url=https://web.archive.org/web/20240110032419/https://www.fda.gov/media/175253/download | archive-date=10 January 2024 | url-status=live }}</ref> |
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In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study.<ref name=blood_adv/> Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related [[macular degeneration]] and some types of [[glomerulopathy|glomerulopathies]].<ref>{{cite journal | vauthors = Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM, Mac Sweeney A, Liao SM, Crowley M, Littlewood-Evans A, Sarret S, Wieczorek G, Perrot L, Dubost V, Flandre T, Zhang Y, Smith RJ, Risitano AM, Karki RG, Zhang C, Valeur E, Sirockin F, Gerhartz B, Erbel P, Hughes N, Smith TM, Cumin F, Argikar UA, Haraldsson B, Mogi M, Sedrani R, Wiesmann C, Jaffee B, Maibaum J, Flohr S, Harrison R, Eder J | display-authors = 6 | title = Small-molecule factor B inhibitor for the treatment of complement-mediated diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 16 | pages = 7926–7931 | date = April 2019 | pmid = 30926668 | doi = 10.1073/pnas.1820892116 | pmc = 6475383 | bibcode = 2019PNAS..116.7926S | doi-access = free }}</ref> |
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== Medical uses == |
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Iptacopan is [[indicated]] for the treatment of adults with paroxysmal nocturnal hemoglobinuria.<ref name="Fabhalta FDA label" /><ref>https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/218276Orig1s000ltr.pdf {{Webarchive|url=https://web.archive.org/web/20231210095630/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/218276Orig1s000ltr.pdf |date=10 December 2023 }} {{PD-notice}}</ref> |
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== Mechanism of action == |
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Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway.<ref>https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf</ref> |
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In [[Paroxysmal nocturnal hemoglobinuria|PNH]], [[intravascular hemolysis]] (IVH) is mediated by the downstream membrane attack complex (MAC), while [[extravascular hemolysis]] (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.<ref>https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf</ref> |
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== Side effects == |
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The FDA label for iptacopan contains a [[black box warning]] for the risk of serious and life-threatening infections caused by encapsulated bacteria, including ''[[Streptococcus pneumoniae]]'', ''[[Neisseria meningitidis]]'', and ''[[Haemophilus influenzae]]'' type B.<ref name="Fabhalta FDA label" /> |
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== Society and culture == |
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=== Legal status === |
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In March 2024, the [[Committee for Medicinal Products for Human Use]] (CHMP) of the [[European Medicines Agency]] (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fabhalta, intended for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).<ref name="Fabhalta EPAR" /><ref>{{cite press release | title=Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2024 | website=European Medicines Agency | date=22 March 2024 | url=https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-18-21-march-2024 | access-date=13 June 2024}}</ref> The applicant for this medicinal product is Novartis Europharm Limited.<ref name="Fabhalta EPAR">{{cite web | title=Fabhalta EPAR | website=[[European Medicines Agency]] (EMA) | date=21 March 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/fabhalta | access-date=23 March 2024}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Iptacopan was approved for medical use in the European Union in May 2024.<ref name="Fabhalta EPAR" /> |
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== Research == |
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In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study.<ref name=blood_adv>{{cite journal | vauthors = Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES | title = Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study | journal = Blood Advances | volume = 6 | issue = 15 | pages = 4450–4460 | date = August 2022 | pmid = 35561315 | doi = 10.1182/bloodadvances.2022006960 | pmc = 9636331 }}</ref><ref>{{cite press release |title=Novartis Phase III APPOINT-PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near-normal levels, leading to transfusion independence in all treatment-naïve PNH patients |url=https://www.novartis.com/news/media-releases/novartis-phase-iii-appoint-pnh-trial-shows-investigational-oral-monotherapy-iptacopan-improves-hemoglobin-near-normal-levels-leading-transfusion-independence-all-treatment-naive-pnh-patients |access-date=6 September 2023 |website=Novartis |archive-date=12 December 2023 |archive-url=https://web.archive.org/web/20231212071556/https://www.novartis.com/news/media-releases/novartis-phase-iii-appoint-pnh-trial-shows-investigational-oral-monotherapy-iptacopan-improves-hemoglobin-near-normal-levels-leading-transfusion-independence-all-treatment-naive-pnh-patients |url-status=live }}</ref> |
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Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related [[macular degeneration]] and some types of [[glomerulopathy|glomerulopathies]].<ref>{{cite journal | vauthors = Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM, Mac Sweeney A, Liao SM, Crowley M, Littlewood-Evans A, Sarret S, Wieczorek G, Perrot L, Dubost V, Flandre T, Zhang Y, Smith RJ, Risitano AM, Karki RG, Zhang C, Valeur E, Sirockin F, Gerhartz B, Erbel P, Hughes N, Smith TM, Cumin F, Argikar UA, Haraldsson B, Mogi M, Sedrani R, Wiesmann C, Jaffee B, Maibaum J, Flohr S, Harrison R, Eder J | title = Small-molecule factor B inhibitor for the treatment of complement-mediated diseases | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 16 | pages = 7926–7931 | date = April 2019 | pmid = 30926668 | doi = 10.1073/pnas.1820892116 | pmc = 6475383 | bibcode = 2019PNAS..116.7926S | doi-access = free }}</ref> |
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== References == |
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== External links == |
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* {{ClinicalTrialsGov|NCT04558918|Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment (APPLY-PNH)}} |
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* {{ClinicalTrialsGov|NCT04820530|Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH)}} |
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Latest revision as of 06:34, 25 June 2024
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| Clinical data | |
|---|---|
| Trade names | Fabhalta |
| Other names | LNP023 |
| AHFS/Drugs.com | Fabhalta |
| License data | |
| Routes of administration | By mouth |
| Drug class | Complement factor B inhibitor |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| PDB ligand | |
| Chemical and physical data | |
| Formula | C25H30N2O4 |
| Molar mass | 422.525 g·mol−1 |
| 3D model (JSmol) | |
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Iptacopan , sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria.[1] It is a complement factor B inhibitor that was developed by Novartis.[1] It is taken by mouth.[1]
Iptacopan was approved by the US Food and Drug Administration (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023.[3][4] The FDA considers it to be a first-in-class medication.[5]
Medical uses
[edit]Iptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria.[1][6]
Mechanism of action
[edit]Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway.[7]
In PNH, intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.[8]
Side effects
[edit]The FDA label for iptacopan contains a black box warning for the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B.[1]
Society and culture
[edit]Legal status
[edit]In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fabhalta, intended for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).[2][9] The applicant for this medicinal product is Novartis Europharm Limited.[2] Iptacopan was approved for medical use in the European Union in May 2024.[2]
Research
[edit]In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study.[10][11]
Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some types of glomerulopathies.[12]
References
[edit]- ^ a b c d e f "Fabhalta- iptacopan capsule". DailyMed. 5 December 2023. Archived from the original on 10 December 2023. Retrieved 10 December 2023.
- ^ a b c d "Fabhalta EPAR". European Medicines Agency (EMA). 21 March 2024. Retrieved 23 March 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ "Novartis receives FDA approval for Fabhalta (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH". Novartis (Press release). Archived from the original on 12 December 2023. Retrieved 6 December 2023.
- ^ "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 6 December 2023. Archived from the original on 21 January 2023. Retrieved 10 December 2023.
- ^ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original on 10 January 2024. Retrieved 9 January 2024.
- ^ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/218276Orig1s000ltr.pdf Archived 10 December 2023 at the Wayback Machine
This article incorporates text from this source, which is in the public domain.
- ^ https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf
- ^ https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf
- ^ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2024". European Medicines Agency (Press release). 22 March 2024. Retrieved 13 June 2024.
- ^ Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, et al. (August 2022). "Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study". Blood Advances. 6 (15): 4450–4460. doi:10.1182/bloodadvances.2022006960. PMC 9636331. PMID 35561315.
- ^ "Novartis Phase III APPOINT-PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near-normal levels, leading to transfusion independence in all treatment-naïve PNH patients". Novartis (Press release). Archived from the original on 12 December 2023. Retrieved 6 September 2023.
- ^ Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM, et al. (April 2019). "Small-molecule factor B inhibitor for the treatment of complement-mediated diseases". Proceedings of the National Academy of Sciences of the United States of America. 116 (16): 7926–7931. Bibcode:2019PNAS..116.7926S. doi:10.1073/pnas.1820892116. PMC 6475383. PMID 30926668.
External links
[edit]- Clinical trial number NCT04558918 for "Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment (APPLY-PNH)" at ClinicalTrials.gov
- Clinical trial number NCT04820530 for "Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH)" at ClinicalTrials.gov
