Duvelisib

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Duvelisib
Duvelisib.svg
Names
Pronunciationdoo-VE-li-SIB
Trade namesCopiktra
  • 8-Chloro-2-phenyl-3-[(1S)-1-(3H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone
Clinical data
Drug classPI3-kinase inhibitor[1]
Main usesChronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), follicular lymphoma[1]
Side effectsDiarrhea, low blood cells, rash, tiredness, fever, liver problems, muscle pains[1]
Routes of
use
By mouth (capsules)
Onset of action1-2 hours after initial administration
Typical dose25 mg BID[2]
External links
AHFS/Drugs.comMonograph
US NLMDuvelisib
MedlinePlusa618056
Legal
License data
Legal status
Pharmacokinetics
Metabolismmainly metabolized by CYP3A4[3]
Elimination half-life5.2 to 10.9 hours
ExcretionFeces (79%), urine (14%)
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.[1] It is used when other treatments have failed.[1] It is taken by mouth.[1]

Common side effects include diarrhea, low blood cells, rash, tiredness, fever, liver problems, and muscle pains.[1] Other serious side effects include inflammation of the lungs, infertility, and infections.[1] Use in pregnancy may harm the baby.[1] It is a dual inhibitor of PI3Kδ and PI3Kγ.[1]

Duvelisib was approved for medical use in the United States in 2018 and Europe in 2021.[1][2] In the United States 4 weeks of treatment costs about 17,200 USD as of 2021.[4]

Medical uses

It is used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed.[1] Further trials are ongoing to confirm benefits as of 2019.[1]

Dosage

It is taken at a dose of 25 mg twice per day.[2]

Mechanism of action

Duvelisib is a Phosphoinositide 3-kinase inhibitor, specifically of the delta and gamma isoforms of PI3K.[5] 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.[5]

History

Duvelisib, also known as IPI-145, was discovered by Intellikine,[6] a company founded in September 2007 based on biochemistry research from the lab of Kevan Shokat at the University of California San Francisco.[7]

In mid-June 2016, Infinity announced results of Phase II clinical trial of duvelisib.[5]

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.[8]

Duvelisib has received orphan drug designation in the United States for treatment of peripheral T-cell lymphoma (PTCL) in 2019.[9]

In September 2020, Duvelisib was sold by Verastem to Secura Bio, Inc. for $70 million and additional payments based on milestones and royalties. [10]

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.[11][12]

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.[13]

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 authorisation for the medicinal product Copiktra, intended for the treatment of adults with relapsed or refractory chronic lymphocytic leukaemia (CLL) and refractory follicular lymphoma (FL).[14] The applicant for this medicinal product is Verastem Europe GmbH.[14]

See also

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 "Duvelisib Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 28 February 2019.
  2. 2.0 2.1 2.2 "Copiktra". Retrieved 27 December 2021.
  3. "Full prescribing information: COPIKTRA (duvelisib)" (PDF). U.S. Food and Drug Administration. Retrieved 23 October 2018.
  4. "Copiktra Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 27 December 2021.
  5. 5.0 5.1 5.2 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.
  6. "Duvelisib". AdisInsight. Retrieved 11 January 2017.
  7. Timmerman L (20 December 2011). "Millennium: Takeda Acquires San Diego's Intellikine for $190M Upfront". Xconomy.
  8. Fidler B (2 November 2016). "Verastem Takes a Low-Cost Flier on Infinity's Blood Cancer Drug". Xconomy.
  9. "Copiktra Receives FDA's Orphan Drug Status for T-cell Lymphoma Treatment". Lymphoma News Today. Retrieved 5 November 2019.
  10. "Verastem Oncology Announces Closing of COPIKTRA® (duvelisib) Sale to Secura Bio".
  11. "Duvelisib (COPIKTRA, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)". FDA. 24 September 2018.
  12. "FDA Accepts New Drug Application for Duvelisib and Grants Priority Review". 2018-07-07.
  13. 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.
  14. 14.0 14.1 "Copiktra: Pending EC decision". European Medicines Agency (EMA). 26 March 2021. Retrieved 26 March 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links

External sites:
Identifiers:
  • "Duvelisib". National Cancer Institute. 17 October 2018.
  • "Duvelisib". NCI Drug Dictionary. National Cancer Institute.