FDA OKs ‘Breakthrough’ Drug Imbruvica
U.S. Food and Drug Administration Approves IMBRUVICA™ (ibrutinib) as a Single Agent for Patients with Mantle Cell LymphomaWho Have Received at Least One Prior Therapy, a rare and aggressive type of blood cancer
Corporate Conference Call Scheduled Today at 10:00 AM PT, November 13, 2013http://www.pharmalive.com/fda-oks-breakthrough-drug-imbruvica
SUNNYVALE, Calif., Nov. 13, 2013 /PRNewswire/ — Pharmacyclics, Inc. (NASDAQ: PCYC) today announced that the U.S. Food and Drug Administration (FDA) has approved IMBRUVICA™ (ibrutinib) as a single agent for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.1 This indication is based on overall response rate (ORR). An improvement in survival or disease-related symptoms has not been established. IMBRUVICA is a new agent that inhibits the function of Bruton’s tyrosine kinase (BTK).1 BTK is a key signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival of malignant B cells.2,3,4 IMBRUVICA blocks signals that stimulate malignant B cells to grow and divide uncontrollably.1,5http://www.pharmalive.com/fda-oks-breakthrough-drug-imbruvica
Ibrutinib (USAN, also known as PCI-32765 and marketed in the U.S. under the name Imbruvica) is a drug approved by the US FDA on November 13, 2013 for the treatment of mantle cell lymphoma. It is an orally-administered, selective and covalent inhibitor of the enzyme Bruton’s tyrosine kinase (BTK). Ibrutinib is currently under development by Pharmacyclics, Inc andJohnson & Johnson‘s Janssen Pharmaceutical division for B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and multiple myeloma. Ibrutinib was first designed and synthesized at Celera Genomics which reported in 2007 a structure-based approach for creating a series of small molecules that inactivate BTK through covalent binding to cysteine-481 near the ATP binding domain of BTK. These small molecules irreversibly inhibited BTK by using a Michael acceptor for binding to the target cysteine. In April 2006, Pharmacyclics acquired Celera’s small molecule BTK inhibitor discovery program, which included a compound, PCI-32765 that was subsequently chosen for further preclinical development based on the discovery of anti-lymphoma properties in vivo. Since 2006, Pharmacyclics’ scientists have advanced the molecule into clinical trials and identified specific clinical indications for the drug. It also has potential effects against autoimmune arthritis.
- Statement on a Nonproprietary Name Adopted by the USAN Council
- FDA Press Release
- Pan, Z; Scheerens, H; Li, SJ; Schultz, BE; Sprengeler, PA; Burrill, LC; Mendonca, RV; Sweeney, MD; Scott, KC; Grothaus, Paul G.; Jeffery, Douglas A.; Spoerke, Jill M.; Honigberg, Lee A.; Young, Peter R.; Dalrymple, Stacie A.; Palmer, James T. (2007). “Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase”. ChemMedChem 2 (1): 58–61.doi:10.1002/cmdc.200600221. PMID 17154430.
- Celera Genomics Announces Sale of Therapeutic Programs to Pharmacyclics
- United States patent 7514444
- Janssen Biotech, Inc. Announces Collaborative Development and Worldwide License Agreement for Investigational Anti-Cancer Drug, PCI-32765
- Clinical trials involve PCI-32765
- Clinical trials involve ibrutinib
- Honigberg, LA; Smith, AM; Sirisawad, M; Verner, E; Loury, D; Chang, B; Li, S; Pan, Z; Thamm, DH; Miller, RA; Buggy, JJ (2010). “The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy”. Proceedings of the National Academy of Sciences of the United States of America 107 (29): 13075–80. doi:10.1073/pnas.1004594107. PMC 2919935.PMID 20615965.
- Chang, BY; Huang, MM; Francesco, M; Chen, J; Sokolove, J; Magadala, P; Robinson, WH; Buggy, JJ (2011). “The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells”. Arthritis Research & Therapy 13 (4): R115. doi:10.1186/ar3400.PMC 3239353. PMID 21752263.