Duvelisib

Last updated
Duvelisib
Duvelisib.svg
Clinical data
Pronunciation doo-VE-li-sib
Trade names Copiktra
AHFS/Drugs.com Monograph
MedlinePlus a618056
License data
Routes of
administration 		By mouth (capsules)
Drug class PI3-Kinase inhibitor
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism mainly metabolized by CYP3A4 [2]
Onset of action 1-2 hours after initial administration
Elimination half-life 5.2 to 10.9 hours
Excretion Feces (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 InfoCard 100.245.560 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H17ClN6O
Molar mass 416.87 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]

Contents

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

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]

Related Research Articles

<span class="mw-page-title-main">Rituximab</span> Biopharmaceutical drug

Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis, idiopathic thrombocytopenic purpura, pemphigus vulgaris, myasthenia gravis and Epstein–Barr virus-positive mucocutaneous ulcers. It is given by slow intravenous infusion.

<span class="mw-page-title-main">Bruton's tyrosine kinase</span> Kinase that plays a role in B cell development

Bruton's tyrosine kinase, also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the BTK gene in humans. BTK plays a crucial role in B cell development.

<span class="mw-page-title-main">Ofatumumab</span> Medication

Ofatumumab is a fully human monoclonal antibody to CD20, which appears to provide rapid B-cell depletion. Under the brand name Kesimpta, it is approved for the treatment of multiple sclerosis in the United States as well as in the European Union and other regions. Under the brand name Arzerra, it is approved for the treatment of certain types of chronic lymphocytic leukemia (CLL) in the United States. It is sold by Novartis under license from Genmab.

<span class="mw-page-title-main">Bendamustine</span> Chemical compound

Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.

Obinutuzumab, sold under the brand name Gazyva among others, is a humanized anti-CD20 monoclonal antibody used as a treatment for cancer. It was originated by GlycArt Biotechnology AG and developed by Roche.

<span class="mw-page-title-main">Phosphoinositide 3-kinase inhibitor</span>

Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.

<span class="mw-page-title-main">Ibrutinib</span> Medication used in cancer treatment

Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia. Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.

<span class="mw-page-title-main">Abexinostat</span> Chemical compound

Abexinostat is an experimental drug candidate for cancer treatment. It was developed by Pharmacyclics and licensed to Xynomic. As of 2013, it was in Phase II clinical trials for B-cell lymphoma. Pre-clinical study suggests the potential for treatment of different types of cancer as well.

<span class="mw-page-title-main">Idelalisib</span> Chemical compound

Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers. Idelalisib acts as a phosphoinositide 3-kinase inhibitor; more specifically, it blocks P110δ, the delta isoform of the enzyme phosphoinositide 3-kinase. It was developed by Gilead Sciences. It is taken orally.

<span class="mw-page-title-main">Copanlisib</span> Chemical compound

Copanlisib, sold under the brand name Aliqopa, is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies.

<span class="mw-page-title-main">Venetoclax</span> Medication

Venetoclax, sold under the brand names Venclexta and Venclyxto, is a medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).

<span class="mw-page-title-main">Acalabrutinib</span> Chemical compound

Acalabrutinib, sold under the brand name Calquence, is a medication used to treat various types of non-Hodgkin lymphoma, including mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic Lymphoma (CLL/SLL). It may be used both in relapsed as well as in treatment-naive settings.

<span class="mw-page-title-main">Umbralisib</span> Chemical compound

Umbralisib, sold under the brand name Ukoniq, is an anti-cancer medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.

Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat B-cell lymphoma and follicular lymphoma.

Verastem, Inc., doing business as Verastem Oncology, is an American pharmaceutical company that develops medicines to treat certain cancers. Headquartered and founded in Boston, Massachusetts, the firm is a member of NASDAQ Biotechnology Index.

<span class="mw-page-title-main">Zanubrutinib</span> Chemical compound

Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL). Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.

BeiGene, Ltd. is a China-based drug developer. It specializes in the development of drugs for cancer treatment. Founded in 2010 by chief executive officer John V. Oyler and Xiaodong Wang, the company is headquartered in Cambridge, Massachusetts and has offices in North America, Europe, South America, Asia and Australia. BeiGene has a large presence in the Chinese market. BeiGene has developed several pharmaceuticals, including tislelizumab, a checkpoint inhibitor, and zanubrutinib, a Bruton's tyrosine kinase inhibitor.

Mosunetuzumab, sold under the brand name Lunsumio, is a monoclonal antibody used for the treatment of follicular lymphoma. It bispecifically binds CD20 and CD3 to engage T-cells. It was developed by Genentech.

<span class="mw-page-title-main">Pirtobrutinib</span> Chemical compound

Pirtobrutinib, sold under the brand name Jaypirca, is an anticancer medication that is used to treat mantle cell lymphoma. It inhibits B cell lymphocyte proliferation and survival by binding and inhibiting Bruton's tyrosine kinase (BTK). It is taken by mouth.

<span class="mw-page-title-main">Orelabrutinib</span> Drug for treatment of cancer

Orelabrutinib is a drug for the treatment of cancer.

References

  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. 1 2 3 "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. 1 2 "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. 1 2 3 4 5 "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. 1 2 3 4 5 6 7 8 9 10 11 "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.PD-icon.svg 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. 1 2 3 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. 1 2 "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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.