Duvelisib

Duvelisib
Clinical data
Pronunciation	doo-VE-li-sib
Trade names	Copiktra
AHFS/Drugs.com	Monograph
MedlinePlus	a618056
License data	US DailyMed: Duvelisib;
Routes of; administration	By mouth (capsules)
Drug class	PI3-Kinase inhibitor
ATC code	L01EM04 (WHO) ;
Legal status
Legal status	US: WARNINGRx-only; EU: Rx-only;
Pharmacokinetic data
Metabolism	mainly metabolized by CYP3A4
Onset of action	1-2 hours after initial administration
Elimination half-life	5.2 to 10.9 hours
Excretion	Feces (79%), urine (14%)
Identifiers
	IUPAC name 8-Chloro-2-phenyl-3-[(1S)-1-(3H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone;
CAS Number	1201438-56-3;
PubChem CID	50905713;
DrugBank	DB11952;
ChemSpider	57251273;
UNII	610V23S0JI;
KEGG	D10555 ; as salt: D11658 ;
ChEMBL	ChEMBLCHEMBL3039502 ;
CompTox Dashboard (EPA)	DTXSID80152697 ;
ECHA InfoCard	100.245.560
Chemical and physical data
Formula	C22H17ClN6O
Molar mass	416.87 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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

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

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

Mechanism of action

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

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

Legal status

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

^ "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.
^ ^a ^b ^c "Copiktra- duvelisib capsule". DailyMed. Archived from the original on 11 November 2021. Retrieved 11 November 2021.
^ "Copiktra- duvelisib capsule". DailyMed. 11 February 2022. Archived from the original on 24 June 2021. Retrieved 30 June 2022.
^ ^a ^b "Copiktra EPAR". European Medicines Agency (EMA). 24 March 2021. Archived from the original on 16 December 2021. Retrieved 11 November 2021.
^ "Copiktra Product information". Union Register of medicinal products. Retrieved 3 March 2023.
^ ^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.
^ ^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. This article incorporates text from this source, which is in the public domain.
^ "duvelisib (Rx)". Medscape. Archived from the original on 21 February 2019. Retrieved 24 September 2018.
^ ^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.
^ "Duvelisib". AdisInsight. Archived from the original on 13 January 2017. Retrieved 11 January 2017.
^ 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.
^ 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.
^ "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.
^ "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.
^ "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.
^ "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.
^ "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.
^ "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.
^ "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.
^ "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.
^ 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.
^ ^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.

External links

"Duvelisib". National Cancer Institute. 17 October 2018.
"Duvelisib". NCI Drug Dictionary. National Cancer Institute.
"FDA warns possible increased risk of death and serious side effects". U.S. Food and Drug Administration. 14 July 2022.

[FDA-AllBoxedWarnings-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.

[Copiktra_FDA_label-2] "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.

[Copiktra_EPAR-4] "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.

[AHFS2019-6] "Duvelisib Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 28 February 2019. Retrieved 28 February 2019.

[FDA_20220630-7] ^ ^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. This article incorporates text from this source, which is in the public domain.

[Medscape-8] "duvelisib (Rx)". Medscape. Archived from the original on 21 February 2019. Retrieved 24 September 2018.

[Anastasia2016rev-9] 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.

[XconomyTakeda-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.

[XconomyVerastem-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.

[biospace-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.

[Copiktra:_Pending_EC_decision-22] "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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Duvelisib

Medical uses

Adverse effects

Pharmacology

Mechanism of action

History

Society and culture

Legal status

References

External links

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