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{{Short description|PI3K inhibitor}}
{{Infobox drug
{{Infobox drug
| IUPAC_name = 8-Chloro-2-phenyl-3-[(1''S'')-1-(3''H''-purin-6-ylamino)ethyl]-1(2''H'')-isoquinolinone
| type = <!-- single chemical drug; default -->
| image = Duvelisib.svg
| image = Duvelisib.svg
| width = 175
| width = 175
| alt =
| pronounce = {{respell|doo|VE|li|SIB}}
| caption =


<!-- Clinical data -->
<!-- Clinical data -->
| pronounce = {{respell|doo|VE|li|sib}}
| tradename = Copiktra
| tradename = Copiktra
| Drugs.com = {{drugs.com|monograph|duvelisib}}
| Drugs.com = {{drugs.com|monograph|duvelisib}}
| MedlinePlus = a618056
| MedlinePlus = a618056
| license_US = Duvelisib
| DailyMedID = Duvelisib
| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment =
| pregnancy_AU_comment =
| pregnancy_US =
| pregnancy_category =
| pregnancy_category =
| routes_of_administration = By mouth ([[Capsule (pharmacy)|capsules]])
| routes_of_administration = [[Oral administration|By mouth]] ([[Capsule (pharmacy)|capsules]])
| class = [[Phosphoinositide 3-kinase inhibitor|PI3-Kinase inhibitor]]
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| ATC_prefix = L01
| legal_AU_comment =
| ATC_suffix = EM04
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| ATC_supplemental =
| legal_DE = <!-- Anlage I, II, III -->

| legal_NZ = <!-- Class A, B, C -->
<!-- Legal status -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Copiktra FDA label">{{cite web | title=Copiktra- duvelisib capsule | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e3c5ac56-e1f6-473a-bc73-687836534780 | access-date=11 November 2021 | archive-date=11 November 2021 | archive-url=https://web.archive.org/web/20211111004630/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e3c5ac56-e1f6-473a-bc73-687836534780 | url-status=live }}</ref><ref>{{cite web | title=Copiktra- duvelisib capsule | website=DailyMed | date=11 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=47547f93-489c-4298-aeea-d6a37ca6cb1d | access-date=30 June 2022 | archive-date=24 June 2021 | archive-url=https://web.archive.org/web/20210624062500/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=47547f93-489c-4298-aeea-d6a37ca6cb1d | url-status=live }}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Copiktra EPAR">{{cite web | title=Copiktra EPAR | website=[[European Medicines Agency]] (EMA) | date=24 March 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/copiktra | access-date=11 November 2021 | archive-date=16 December 2021 | archive-url=https://web.archive.org/web/20211216171702/https://www.ema.europa.eu/en/medicines/human/EPAR/copiktra | url-status=live }}</ref><ref>{{cite web | title=Copiktra Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1542.htm | access-date=3 March 2023}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!-- Pharmacokinetic data -->
<!-- Pharmacokinetic data -->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism = mainly metabolized by CYP3A4<ref>{{cite web|title=Full prescribing information: COPIKTRA (duvelisib)|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/211155s000lbl.pdf|website=U.S. Food and Drug Administration |accessdate=23 October 2018}}</ref>
| metabolism = mainly metabolized by CYP3A4<ref name="Copiktra FDA label" />
| metabolites =
| metabolites =
| onset = 1-2 hours after initial administration
| onset = 1-2 hours after initial administration
Line 36: Line 53:


<!-- Identifiers -->
<!-- Identifiers -->
| index2_label = as salt
| CAS_number = 1201438-56-3
| CAS_number = 1201438-56-3
| CAS_supplemental =
| class = [[Phosphoinositide 3-kinase inhibitor|PI3-Kinase inhibitor]]
| PubChem = 50905713
| IUPHAR_ligand =
| DrugBank = DB11952
| DrugBank = DB11952
| ChemSpiderID = 57251273
| ChemSpiderID = 57251273
| ATCvet =
| ATC_prefix = none
| ATC_suffix =
| UNII = 610V23S0JI
| UNII = 610V23S0JI
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = CHEMBL3039502
| PubChem = 50905713
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D10555
| KEGG = D10555
| KEGG2_Ref = {{keggcite|correct|kegg}}
| KEGG2 = D11658
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = CHEMBL3039502
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =


<!-- Chemical data -->
<!-- Chemical and physical data -->
| IUPAC_name = 8-Chloro-2-phenyl-3-[(1''S'')-1-(3''H''-purin-6-ylamino)ethyl]-1(2''H'')-isoquinolinone
| chemical_formula = C<sub>22</sub>H<sub>17</sub>ClN<sub>6</sub>O
| C = 22 | H = 17 | Cl = 1 | N = 6 | O = 1
| molecular_weight = 416.86 g/mol
| smiles = C[C@@H](C1=CC2=C(C(=CC=C2)Cl)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
| SMILES = C[C@@H](C1=CC2=C(C(=CC=C2)Cl)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5
| StdInChI =
| StdInChI_comment =
| StdInChIKey = SJVQHLPISAIATJ-ZDUSSCGKSA-N
| StdInChIKey = SJVQHLPISAIATJ-ZDUSSCGKSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}

<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Duvelisib''', sold under the brand name '''Copiktra''', is a medication used to treat [[chronic lymphocytic leukemia]] (CLL) or [[small lymphocytic lymphoma]] (SLL) after other treatments have failed.<ref name=AHFS2019/> It is taken by mouth.<ref name=AHFS2019>{{cite web |title=Duvelisib Monograph for Professionals |url=https://www.drugs.com/monograph/duvelisib.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |accessdate=28 February 2019 |language=en}}</ref>
'''Duvelisib''', sold under the brand name '''Copiktra''', is a [[medication]] used to treat [[chronic lymphocytic leukemia]] (CLL), [[small lymphocytic lymphoma]] (SLL), and [[follicular lymphoma]] after other treatments have failed.<ref name=AHFS2019/> It is taken by mouth.<ref name=AHFS2019>{{cite web |title=Duvelisib Monograph for Professionals |url=https://www.drugs.com/monograph/duvelisib.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=28 February 2019 |archive-date=28 February 2019 |archive-url=https://web.archive.org/web/20190228192020/https://www.drugs.com/monograph/duvelisib.html |url-status=live }}</ref> It is a [[Phosphoinositide 3-kinase inhibitor|PI3 kinase inhibitor]].<ref name="FDA 20220630" />


<!-- Side effects and mechanisms -->
<!-- Side effects and mechanisms -->
Common side effects include diarrhea, [[low white blood cells]], rash, feeling tired, fever, and muscle pains.<ref name=AHFS2019/> Other serious side effects include [[pneumonitis|inflammation of the lungs]] and infections.<ref name=AHFS2019/> It is a dual inhibitor of [[P110δ|PI3Kδ]] and [[PIK3CG|PI3Kγ]].<ref name=Medscape>{{cite news |url=https://reference.medscape.com/drug/copiktra-duvelisib-1000261 |title=duvelisib (Rx) |website=Medscape |accessdate=24 September 2018}}</ref> Duvelisib is manufactured by [[Verastem Oncology]].
Common side effects include diarrhea, [[low white blood cells]], rash, feeling tired, fever, and muscle pains.<ref name=AHFS2019/> Other serious side effects include [[pneumonitis|inflammation of the lungs]] and infections.<ref name=AHFS2019/> It is a dual inhibitor of [[P110δ|PI3Kδ]] and [[PIK3CG|PI3Kγ]].<ref name=Medscape>{{cite news |url=https://reference.medscape.com/drug/copiktra-duvelisib-1000261 |title=duvelisib (Rx) |website=Medscape |access-date=24 September 2018 |archive-date=21 February 2019 |archive-url=https://web.archive.org/web/20190221112404/https://reference.medscape.com/drug/copiktra-duvelisib-1000261 |url-status=live }}</ref>


==Medical uses==
== Medical uses ==
It is used to treat [[chronic lymphocytic leukemia]] (CLL), [[small lymphocytic lymphoma]] (SLL), and [[follicular lymphoma]] after other treatments have failed.<ref name=AHFS2019/> Further trials are ongoing to confirm benefits as of 2019.<ref name=AHFS2019/>
Duvelisib is [[indicated]] to treat adults with [[chronic lymphocytic leukemia]] (CLL) or [[small lymphocytic lymphoma]] (SLL) who have received at least two prior therapies that did not work or stopped working.<ref name="Copiktra FDA label" /><ref name=AHFS2019/><ref name="FDA 20220630" /> CLL is a type of cancer that begins in the white blood cells, and SLL is a type of cancer that begins mostly in the lymph nodes.<ref name="FDA 20220630" />


== Adverse effects ==
==Mechanism of action==
Duvelisib may cause infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood.<ref name="FDA 20220630">{{cite web | title=FDA warns possible increased risk of death and serious side effects | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 June 2022 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-possible-increased-risk-death-and-serious-side-effects-cancer-drug-copiktra | access-date=30 June 2022 | archive-date=30 June 2022 | archive-url=https://web.archive.org/web/20220630160438/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-possible-increased-risk-death-and-serious-side-effects-cancer-drug-copiktra | url-status=live }} {{PD-notice}}</ref>

Patients taking duvelisib may have a higher risk of death.<ref name="FDA 20220630" />

== Pharmacology ==
=== Mechanism of action ===
Duvelisib is a [[Phosphoinositide 3-kinase inhibitor]], specifically of the delta and gamma isoforms of PI3K.<ref name=Anastasia2016rev/> This class of compounds works by preventing PI3K from playing its role in [[Signal transduction|transducing signals]] from outside of cells into various intracellular pathways involved in cell cycle regulation, apoptosis, DNA repair, senescence, angiogenesis and cell metabolism, including the [[PI3K/AKT/mTOR pathway]].<ref name=Anastasia2016rev/>
Duvelisib is a [[Phosphoinositide 3-kinase inhibitor]], specifically of the delta and gamma isoforms of PI3K.<ref name=Anastasia2016rev/> This class of compounds works by preventing PI3K from playing its role in [[Signal transduction|transducing signals]] from outside of cells into various intracellular pathways involved in cell cycle regulation, apoptosis, DNA repair, senescence, angiogenesis and cell metabolism, including the [[PI3K/AKT/mTOR pathway]].<ref name=Anastasia2016rev/>


==History==
==History==
Duvelisib, also known as IPI-145, was discovered by Intellikine,<ref>{{cite web|title=Duvelisib|url=http://adisinsight.springer.com/drugs/800035173|publisher=AdisInsight|accessdate=11 January 2017}}</ref> a company founded in September 2007 based on biochemistry research from the lab of [[Kevan Shokat]] at the [[University of California, San Francisco|University of California San Francisco]].<ref name=XconomyTakeda>{{cite news|last1=Timmerman|first1=Luke|title=Millennium: Takeda Acquires San Diego's Intellikine for $190M Upfront|url=http://www.xconomy.com/boston/2011/12/20/millennium-takeda-acquires-san-diegos-intellikine-for-190m-upfront/|work=Xconomy|date=20 December 2011}}</ref>
Duvelisib, also known as IPI-145, was discovered by Intellikine,<ref>{{cite web|title=Duvelisib|url=http://adisinsight.springer.com/drugs/800035173|publisher=AdisInsight|access-date=11 January 2017|archive-date=13 January 2017|archive-url=https://web.archive.org/web/20170113141345/http://adisinsight.springer.com/drugs/800035173|url-status=live}}</ref> a company founded in September 2007 based on biochemistry research from the lab of [[Kevan Shokat]] at the [[University of California, San Francisco|University of California San Francisco]].<ref name=XconomyTakeda>{{cite news|last1=Timmerman|first1=Luke|name-list-style=vanc|title=Millennium: Takeda Acquires San Diego's Intellikine for $190M Upfront|url=http://www.xconomy.com/boston/2011/12/20/millennium-takeda-acquires-san-diegos-intellikine-for-190m-upfront/|work=Xconomy|date=20 December 2011|access-date=11 January 2017|archive-date=20 April 2021|archive-url=https://web.archive.org/web/20210420223109/https://xconomy.com/boston/2011/12/20/millennium-takeda-acquires-san-diegos-intellikine-for-190m-upfront/|url-status=live}}</ref>


In mid-June 2016, Infinity announced results of Phase II clinical trial of duvelisib.<ref name=Anastasia2016rev>{{cite journal|last1=Anastasia|first1=A|last2=Rossi|first2=G|title=Novel Drugs in Follicular Lymphoma.|journal=Mediterranean journal of hematology and infectious diseases|date=1 November 2016|volume=8|issue=1|pages=e2016061|pmid=27872741|pmc=5111511|doi=10.4084/MJHID.2016.061}}</ref>
In mid-June 2016, Infinity announced results of Phase II clinical trial of duvelisib.<ref name=Anastasia2016rev>{{cite journal | vauthors = Anastasia A, Rossi G | title = Novel Drugs in Follicular Lymphoma | journal = Mediterranean Journal of Hematology and Infectious Diseases | volume = 8 | issue = 1 | pages = e2016061 | date = 1 November 2016 | pmid = 27872741 | pmc = 5111511 | doi = 10.4084/MJHID.2016.061 }}</ref>


In November 2016, Infinity exclusively licensed the worldwide rights to duvelisib to Verastem Oncology for little money compared to earlier deals; the deal included no upfront payment, a $6 million milestone for success in a Phase 3 trial in chronic lymphocytic leukemia, a $22 million payment for an FDA approval, and royalties.<ref name=XconomyVerastem>{{cite news|last1=Fidler|first1=Ben|title=Verastem Takes a Low-Cost Flier on Infinity’s Blood Cancer Drug|url=http://www.xconomy.com/boston/2016/11/02/verastem-takes-a-low-cost-flier-on-infinitys-blood-cancer-drug/|work=Xconomy|date=2 November 2016}}</ref>
In November 2016, Infinity exclusively licensed the worldwide rights to duvelisib to Verastem Oncology for little money compared to earlier deals; the deal included no upfront payment, a $6 million milestone for success in a Phase 3 trial in chronic lymphocytic leukemia, a $22 million payment for an FDA approval, and royalties.<ref name=XconomyVerastem>{{cite news|last1=Fidler|first1=Ben|name-list-style=vanc|title=Verastem Takes a Low-Cost Flier on Infinity's Blood Cancer Drug|url=http://www.xconomy.com/boston/2016/11/02/verastem-takes-a-low-cost-flier-on-infinitys-blood-cancer-drug/|work=Xconomy|date=2 November 2016|access-date=11 January 2017|archive-date=21 April 2021|archive-url=https://web.archive.org/web/20210421170813/https://xconomy.com/boston/2016/11/02/verastem-takes-a-low-cost-flier-on-infinitys-blood-cancer-drug/|url-status=live}}</ref>


Duvelisib received [[orphan drug]] designation in the United States for the treatment of peripheral [[T-cell lymphoma]] (PTCL) in 2019,<ref>{{cite web | title=Duvelisib Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=2 October 2019 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=703019 | access-date=30 June 2022 | archive-date=23 November 2020 | archive-url=https://web.archive.org/web/20201123093255/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=703019 | url-status=live }}</ref><ref>{{cite web|title=Copiktra Receives FDA's Orphan Drug Status for T-cell Lymphoma Treatment|date=10 October 2019 |url=https://lymphomanewstoday.com/2019/10/10/copiktra-receives-fda-orphan-drug-designation-for-t-cell-lymphoma/|publisher=Lymphoma News Today|access-date=5 November 2019|archive-date=6 November 2019|archive-url=https://web.archive.org/web/20191106033125/https://lymphomanewstoday.com/2019/10/10/copiktra-receives-fda-orphan-drug-designation-for-t-cell-lymphoma/|url-status=live}}</ref> the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma in 2013,<ref>{{cite web | title=Duvelisib Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=15 April 2013 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=394413 | access-date=30 June 2022 | archive-date=24 October 2020 | archive-url=https://web.archive.org/web/20201024071123/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=394413 | url-status=live }}</ref> and the treatment of follicular lymphoma in 2013.<ref>{{cite web | title=Duvelisib Orphan Drug Designations and Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=1 August 2013 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=399913 | access-date=30 June 2022 | archive-date=24 October 2020 | archive-url=https://web.archive.org/web/20201024063245/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=399913 | url-status=live }}</ref>
==Approvals==


In September 2020, duvelisib was sold by Verastem to Secura Bio, Inc. for $70 million and additional payments based on milestones and royalties.<ref name="biospace">{{cite web | title=Verastem Oncology Announces Closing of Copiktra (duvelisib) Sale to Secura Bio | date=30 September 2020 | url=https://www.biospace.com/article/releases/verastem-oncology-announces-closing-of-copiktra-duvelisib-sale-to-secura-bio/ | access-date=2021-02-19 | archive-date=2021-04-24 | archive-url=https://web.archive.org/web/20210424033244/https://www.biospace.com/article/releases/verastem-oncology-announces-closing-of-copiktra-duvelisib-sale-to-secura-bio/ | url-status=live }}</ref>
In April 2018, Verastem filed a New Drug Application (NDA) for duvelisib for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for relapsed or refractory follicular lymphoma (FL). The FDA approved the application in September 2018.<ref>{{cite news|title=Duvelisib (COPIKTRA, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm621503.htm|work=FDA|date=24 September 2018}}</ref><ref>{{Cite news|url=https://www.businesswire.com/news/home/20180409005377/en/FDA-Accepts-New-Drug-Application-Duvelisib-Grants|title=FDA Accepts New Drug Application for Duvelisib and Grants Priority Review |date=2018-07-07}}</ref>


The US [[Food and Drug Administration]] (FDA) required the drug manufacturer, Secura Bio, to submit the final 5-year survival results from the clinical trial, called DUO trial, a phase III, randomized, open-label trial.<ref name="FDA 20220630" /> It was conducted in 319 participants with CLL or SLL who received a previous therapy that did not work or stopped working.<ref name="FDA 20220630" /> These final results showed a possible increased risk of death with duvelisib compared to the monoclonal antibody ofatumumab.<ref name="FDA 20220630" /> The rate of serious side effects, dose modifications, and deaths resulting from these side effects were also higher among participants who received duvelisib.<ref name="FDA 20220630" /> The serious side effects included infections, diarrhea, inflammation of the intestine and lungs, skin reactions, and elevated liver enzyme levels in the blood.<ref name="FDA 20220630" /> These safety findings were similar for other medicines in the same PI3 kinase inhibitor class.<ref name="FDA 20220630" />
Duvelisib is intended to be used in patients who have received at least two prior systemic therapies, and carries a [[black box warning]] due to the risk of fatal/serious toxicities: infections, diarrhea or colitis, cutaneous reactions and pneumonitis.<ref>{{cite news|last1=Carroll|first1=John|title=Unwanted by AbbVie and Infinity, battered Verastem gets an OK for duvelisib and a second shot at success |url=https://endpts.com/unwanted-by-abbvie-and-infinity-verastem-gets-an-ok-for-duvelisib-and-a-second-shot-at-success/ |work=Endpoints News|date=24 September 2018}}</ref>


== Society and culture ==
==See also==
* [[Phosphoinositide 3-kinase inhibitor]]
* [[Idelalisib]]


=== Legal status ===
==References==
In April 2018, Verastem filed a New Drug Application (NDA) for duvelisib for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for relapsed or refractory follicular lymphoma (FL). The FDA approved the application in September 2018.<ref>{{cite news|title=Duvelisib (Copiktra, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm621503.htm|work=FDA|date=24 September 2018|access-date=1 February 2019|archive-date=23 April 2019|archive-url=https://web.archive.org/web/20190423133242/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm621503.htm|url-status=live}}</ref><ref>{{Cite press release |url=https://www.businesswire.com/news/home/20180409005377/en/FDA-Accepts-New-Drug-Application-Duvelisib-Grants |title=FDA Accepts New Drug Application for Duvelisib and Grants Priority Review |date=2018-07-07 |publisher=Verastem |via=Business Wire |access-date=2019-02-01 |archive-date=2021-04-19 |archive-url=https://web.archive.org/web/20210419111450/https://www.businesswire.com/news/home/20180409005377/en/FDA-Accepts-New-Drug-Application-Duvelisib-Grants |url-status=live }}</ref> In April 2022, the FDA withdrew the approval of duvelisib for relapsed or refractory follicular lymphoma on request of its then owner, Secura Bio.<ref>{{cite web|url=https://www.federalregister.gov/documents/2022/04/13/2022-07931/secura-bio-inc-withdrawal-of-approval-of-relapsed-or-refractory-follicular-lymphoma-indication-for|date=2022-04-13|accessdate=2022-05-03|title=Secura Bio, Inc.; Withdrawal of Approval of Relapsed or Refractory Follicular Lymphoma Indication for Copiktra|archive-date=2022-04-13|archive-url=https://web.archive.org/web/20220413085855/https://www.federalregister.gov/documents/2022/04/13/2022-07931/secura-bio-inc-withdrawal-of-approval-of-relapsed-or-refractory-follicular-lymphoma-indication-for|url-status=live}}</ref>

Duvelisib is intended to be used in people who have received at least two prior systemic therapies, and carries a [[black box warning]] due to the risk of fatal/serious toxicities: infections, diarrhea or colitis, cutaneous reactions and pneumonitis.<ref>{{cite news|last1=Carroll|first1=John|name-list-style=vanc|title=Unwanted by AbbVie and Infinity, battered Verastem gets an OK for duvelisib and a second shot at success|url=https://endpts.com/unwanted-by-abbvie-and-infinity-verastem-gets-an-ok-for-duvelisib-and-a-second-shot-at-success/|work=Endpoints News|date=24 September 2018|access-date=1 February 2019|archive-date=20 April 2021|archive-url=https://web.archive.org/web/20210420223110/https://endpts.com/unwanted-by-abbvie-and-infinity-verastem-gets-an-ok-for-duvelisib-and-a-second-shot-at-success/|url-status=live}}</ref>

On 25 March 2021, 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 Copiktra, intended for the treatment of adults with relapsed or refractory chronic lymphocytic leukaemia (CLL) and refractory follicular lymphoma (FL).<ref name="Copiktra: Pending EC decision" /> The applicant for this medicinal product is Verastem Europe GmbH.<ref name="Copiktra: Pending EC decision">{{cite web | title=Copiktra: Pending EC decision | website=[[European Medicines Agency]] (EMA) | date=26 March 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/copiktra | access-date=26 March 2021 | archive-date=26 March 2021 | archive-url=https://web.archive.org/web/20210326111756/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/copiktra | url-status=dead }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Duvelisib was approved for medical use in the European Union in May 2021.<ref name="Copiktra EPAR" />

== References ==
{{reflist}}
{{reflist}}


==External links==
== External links ==
* {{cite web | title=Duvelisib | website=National Cancer Institute | date=17 October 2018 | url=https://www.cancer.gov/about-cancer/treatment/drugs/duvelisib }}
* {{cite web | title=Duvelisib | work=NCI Drug Dictionary | publisher=National Cancer Institute | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/duvelisib }}
* {{cite web | title=FDA warns possible increased risk of death and serious side effects | website=U.S. Food and Drug Administration | date=14 July 2022 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-possible-increased-risk-death-and-serious-side-effects-cancer-drug-copiktra }}

{{Chemotherapeutic agents}}
{{Portal bar | Medicine}}


[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Antineoplastic drugs]]
[[Category:Antineoplastic drugs]]
[[Category:Kinase inhibitors]]
[[Category:Phosphoinositide 3-kinase inhibitors]]
[[Category:Protein kinase inhibitors]]
[[Category:Orphan drugs]]

Latest revision as of 15:43, 18 October 2024

Duvelisib
Clinical data
Pronunciationdoo-VE-li-sib
Trade namesCopiktra
AHFS/Drugs.comMonograph
MedlinePlusa618056
License data
Routes of
administration		By mouth (capsules)
Drug classPI3-Kinase inhibitor
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolismmainly metabolized by CYP3A4[2]
Onset of action1-2 hours after initial administration
Elimination half-life5.2 to 10.9 hours
ExcretionFeces (79%), urine (14%)
Identifiers
  • 8-Chloro-2-phenyl-3-[(1S)-1-(3H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.245.560 Edit this at Wikidata
Chemical and physical data
FormulaC22H17ClN6O
Molar mass416.87 g·mol−1
3D model (JSmol)
  • C[C@@H](C1=CC2=C(C(=CC=C2)Cl)C(=O)N1C3=CC=CC=C3)NC4=NC=NC5=C4NC=N5

Duvelisib, sold under the brand name Copiktra, is a medication used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed.[6] It is taken by mouth.[6] It is a PI3 kinase inhibitor.[7]

Common side effects include diarrhea, low white blood cells, rash, feeling tired, fever, and muscle pains.[6] Other serious side effects include inflammation of the lungs and infections.[6] It is a dual inhibitor of PI3Kδ and PI3Kγ.[8]

Medical uses

[edit]

Duvelisib is indicated to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior therapies that did not work or stopped working.[2][6][7] CLL is a type of cancer that begins in the white blood cells, and SLL is a type of cancer that begins mostly in the lymph nodes.[7]

Adverse effects

[edit]

Duvelisib may cause infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood.[7]

Patients taking duvelisib may have a higher risk of death.[7]

Pharmacology

[edit]

Mechanism of action

[edit]

Duvelisib is a Phosphoinositide 3-kinase inhibitor, specifically of the delta and gamma isoforms of PI3K.[9] This class of compounds works by preventing PI3K from playing its role in transducing signals from outside of cells into various intracellular pathways involved in cell cycle regulation, apoptosis, DNA repair, senescence, angiogenesis and cell metabolism, including the PI3K/AKT/mTOR pathway.[9]

History

[edit]

Duvelisib, also known as IPI-145, was discovered by Intellikine,[10] a company founded in September 2007 based on biochemistry research from the lab of Kevan Shokat at the University of California San Francisco.[11]

In mid-June 2016, Infinity announced results of Phase II clinical trial of duvelisib.[9]

In November 2016, Infinity exclusively licensed the worldwide rights to duvelisib to Verastem Oncology for little money compared to earlier deals; the deal included no upfront payment, a $6 million milestone for success in a Phase 3 trial in chronic lymphocytic leukemia, a $22 million payment for an FDA approval, and royalties.[12]

Duvelisib received orphan drug designation in the United States for the treatment of peripheral T-cell lymphoma (PTCL) in 2019,[13][14] the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma in 2013,[15] and the treatment of follicular lymphoma in 2013.[16]

In September 2020, duvelisib was sold by Verastem to Secura Bio, Inc. for $70 million and additional payments based on milestones and royalties.[17]

The US Food and Drug Administration (FDA) required the drug manufacturer, Secura Bio, to submit the final 5-year survival results from the clinical trial, called DUO trial, a phase III, randomized, open-label trial.[7] It was conducted in 319 participants with CLL or SLL who received a previous therapy that did not work or stopped working.[7] These final results showed a possible increased risk of death with duvelisib compared to the monoclonal antibody ofatumumab.[7] The rate of serious side effects, dose modifications, and deaths resulting from these side effects were also higher among participants who received duvelisib.[7] The serious side effects included infections, diarrhea, inflammation of the intestine and lungs, skin reactions, and elevated liver enzyme levels in the blood.[7] These safety findings were similar for other medicines in the same PI3 kinase inhibitor class.[7]

Society and culture

[edit]
[edit]

In April 2018, Verastem filed a New Drug Application (NDA) for duvelisib for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for relapsed or refractory follicular lymphoma (FL). The FDA approved the application in September 2018.[18][19] In April 2022, the FDA withdrew the approval of duvelisib for relapsed or refractory follicular lymphoma on request of its then owner, Secura Bio.[20]

Duvelisib is intended to be used in people who have received at least two prior systemic therapies, and carries a black box warning due to the risk of fatal/serious toxicities: infections, diarrhea or colitis, cutaneous reactions and pneumonitis.[21]

On 25 March 2021, 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 Copiktra, intended for the treatment of adults with relapsed or refractory chronic lymphocytic leukaemia (CLL) and refractory follicular lymphoma (FL).[22] The applicant for this medicinal product is Verastem Europe GmbH.[22] Duvelisib was approved for medical use in the European Union in May 2021.[4]

References

[edit]
  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ a b c "Copiktra- duvelisib capsule". DailyMed. Archived from the original on 11 November 2021. Retrieved 11 November 2021.
  3. ^ "Copiktra- duvelisib capsule". DailyMed. 11 February 2022. Archived from the original on 24 June 2021. Retrieved 30 June 2022.
  4. ^ a b "Copiktra EPAR". European Medicines Agency (EMA). 24 March 2021. Archived from the original on 16 December 2021. Retrieved 11 November 2021.
  5. ^ "Copiktra Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  6. ^ a b c d e "Duvelisib Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 28 February 2019. Retrieved 28 February 2019.
  7. ^ a b c d e f g h i j k "FDA warns possible increased risk of death and serious side effects". U.S. Food and Drug Administration (FDA). 30 June 2022. Archived from the original on 30 June 2022. Retrieved 30 June 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ "duvelisib (Rx)". Medscape. Archived from the original on 21 February 2019. Retrieved 24 September 2018.
  9. ^ a b c Anastasia A, Rossi G (1 November 2016). "Novel Drugs in Follicular Lymphoma". Mediterranean Journal of Hematology and Infectious Diseases. 8 (1): e2016061. doi:10.4084/MJHID.2016.061. PMC 5111511. PMID 27872741.
  10. ^ "Duvelisib". AdisInsight. Archived from the original on 13 January 2017. Retrieved 11 January 2017.
  11. ^ Timmerman L (20 December 2011). "Millennium: Takeda Acquires San Diego's Intellikine for $190M Upfront". Xconomy. Archived from the original on 20 April 2021. Retrieved 11 January 2017.
  12. ^ Fidler B (2 November 2016). "Verastem Takes a Low-Cost Flier on Infinity's Blood Cancer Drug". Xconomy. Archived from the original on 21 April 2021. Retrieved 11 January 2017.
  13. ^ "Duvelisib Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 2 October 2019. Archived from the original on 23 November 2020. Retrieved 30 June 2022.
  14. ^ "Copiktra Receives FDA's Orphan Drug Status for T-cell Lymphoma Treatment". Lymphoma News Today. 10 October 2019. Archived from the original on 6 November 2019. Retrieved 5 November 2019.
  15. ^ "Duvelisib Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 15 April 2013. Archived from the original on 24 October 2020. Retrieved 30 June 2022.
  16. ^ "Duvelisib Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 1 August 2013. Archived from the original on 24 October 2020. Retrieved 30 June 2022.
  17. ^ "Verastem Oncology Announces Closing of Copiktra (duvelisib) Sale to Secura Bio". 30 September 2020. Archived from the original on 2021-04-24. Retrieved 2021-02-19.
  18. ^ "Duvelisib (Copiktra, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)". FDA. 24 September 2018. Archived from the original on 23 April 2019. Retrieved 1 February 2019.
  19. ^ "FDA Accepts New Drug Application for Duvelisib and Grants Priority Review" (Press release). Verastem. 2018-07-07. Archived from the original on 2021-04-19. Retrieved 2019-02-01 – via Business Wire.
  20. ^ "Secura Bio, Inc.; Withdrawal of Approval of Relapsed or Refractory Follicular Lymphoma Indication for Copiktra". 2022-04-13. Archived from the original on 2022-04-13. Retrieved 2022-05-03.
  21. ^ Carroll J (24 September 2018). "Unwanted by AbbVie and Infinity, battered Verastem gets an OK for duvelisib and a second shot at success". Endpoints News. Archived from the original on 20 April 2021. Retrieved 1 February 2019.
  22. ^ a b "Copiktra: Pending EC decision". European Medicines Agency (EMA). 26 March 2021. Archived from the original on 26 March 2021. Retrieved 26 March 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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