|By mouth (capsules)|
|Drug class||PI3-Kinase inhibitor|
|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%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||416.86 g/mol|
|3D model (JSmol)|
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. It is taken by mouth.
Common side effects include diarrhea, low white blood cells, rash, feeling tired, fever, and muscle pains. Other serious side effects include inflammation of the lungs and infections. It is a dual inhibitor of PI3Kδ and PI3Kγ. Duvelisib is manufactured by Verastem Oncology.
It is used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed. Further trials are ongoing to confirm benefits as of 2019.
Mechanism of action
Duvelisib is a Phosphoinositide 3-kinase inhibitor, specifically of the delta and gamma isoforms of PI3K. 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.
Duvelisib, also known as IPI-145, was discovered by Intellikine, a company founded in September 2007 based on biochemistry research from the lab of Kevan Shokat at the University of California San Francisco.
In mid-June 2016, Infinity announced results of Phase II clinical trial of duvelisib.
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.
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.
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.
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- Timmerman, Luke (20 December 2011). "Millennium: Takeda Acquires San Diego's Intellikine for $190M Upfront". Xconomy.
- Fidler, Ben (2 November 2016). "Verastem Takes a Low-Cost Flier on Infinity's Blood Cancer Drug". Xconomy.
- "Duvelisib (COPIKTRA, Verastem, Inc.) for adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)". FDA. 24 September 2018.
- "FDA Accepts New Drug Application for Duvelisib and Grants Priority Review". 2018-07-07.
- Carroll, John (24 September 2018). "Unwanted by AbbVie and Infinity, battered Verastem gets an OK for duvelisib and a second shot at success". Endpoints News.