AbbVie to buy Pharmacyclics for pipeline boost 10 March 2015 Andrew Turley AbbVie has agreed to buy US biotech Pharmacyclics for $21 billion (£14 billion) in a bid to re-stock its pipeline. The move grants AbbVie a share of future sales of anticancer drug Imbruvica (ibrutinib), which launched in December 2013 and generated $548 million in sales in 2014. Peak sales of the drug are expected to reach $6 billion per year. Whether this will be enough to justify the price of the deal, however, remains to be seen. Pharmacyclics already has a 50:50 marketing deal for Imbruvica with Janssen (part of Johnson & Johnson), so AbbVie will only be entitled to half of the income. Pharmacyclics has three other candidates in its pipeline, but none has yet progressed beyond Phase II trials. Nonetheless, Imbruvica will provide a much needed boost to AbbVie's portfolio. The kinase inhibitor is already approved for three blood and lymphatic system cancers, and Pharmacyclics is investigating its effectiveness in seven other conditions. AbbVie owns anti-inflammatory antibody Humira (adalimumab), which is currently the best selling drug in the world, with $10.7 billion in sales in 2013. But its patent protection will expire in late 2016, opening the door to generic competition from biosimilar versions. This has pushed the company to top up its pipeline with deals. In July 2014, the firm entered a $55 billion merger with Shire, which would have allowed AbbVie to cut its US tax bill, by registering the new company in the UK. But AbbVie abandoned the deal in October 2014, after the US government changed the rules covering so-called 'tax inversions'. The current deal highlights a remarkable turnaround in fortunes for Pharmacyclics. The company was founded in 1991, but it was not until 2006 that acquired the basis for ibrutinib from US genetic sequencing firm Celera. In 2007, the US Food and Drug Administration (FDA) rejected anticancer candidate Xcytrin (motexafin gadolinium). It was then hit hard by the economic crash of 2007–2008. In 2009, the shares changed hands for about $1 each. Now, AbbVie has agreed to pay $261 per Pharmacyclics share. This means that someone who had invested £4000 in 2009 would have made £1 million in six years.'There is a noteworthy synergy with AbbVie's oncology pipeline, which is itself expected to deliver peak annual revenues of $3 billion,' says Joshua Owide, director of healthcare industry dynamics at market research firm GlobalData. AbbVie will have the eighth most valuable oncology portfolio in the sector. 'While the Pharmacyclics deal is very costly, there is an opportunity for AbbVie to derive value from the deal in the long term, as well as use Imbruvica as a springboard for its strategic move into oncology.' Owide expects ibrutinib to generate sales of more than $40 billion over 15 years.
FDA expands approved use of Imbruvica for rare form of non-Hodgkin lymphoma First drug approved to treat Waldenström's macroglobulinemia FDA January 29, 2015 Release The U.S. Food and Drug Administration today expanded the approved use of Imbruvica (ibrutinib) for patients with Waldenström's macroglobulinemia (WM), a rare form of cancer that begins in the body's immune system. The drug received a breakthrough therapy designation for this use. A type of non-Hodgkin lymphoma, WM usually gets worse slowly over time and causes abnormal blood cells, known as B lymphocytes (B-cells), to grow within the bone marrow, lymph nodes, liver, and spleen. In WM, abnormal B-cells also overproduce a protein known as immunoglobulin M or IgM (macroglobulin) that may lead to excess bleeding, problems with vision and with the nervous system. According to the National Cancer Institute, approximately 70,800 Americans were diagnosed and 18,990 died from non-Hodgkin lymphomas in 2014. Imbruvica works by blocking the enzyme that allows the abnormal B-cells in WM to grow and divide. "Today's approval highlights the importance of development of drugs for supplemental indications," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research. "Continued research has discovered new uses of Imbruvica." The FDA initially granted Imbruvica accelerated approval in November 2013 for use in patients with mantle cell lymphoma who received one prior therapy. In February 2014, the FDA granted accelerated approval to Imbruvica for use in patients with previously treated chronic lymphocytic leukemia (CLL), and then in July 2014, expanded its use to include treatment of CLL patients who carry a deletion in chromosome 17. The FDA based its approval of Imbruvica for WM on a clinical study of 63 previously treated participants. All study participants received a daily 420 milligram orally administered dose of the medication until disease progression or side effects became intolerable. Results showed 62 percent of participants had their cancer shrink after treatment (overall response rate). At the time of the study, the duration of response ranged from 2.8 months to approximately 18.8 months. The most common side effects associated with the drug are low blood platelet counts (thrombocytopenia), a decrease in infection-fighting white blood cells (neutropenia), diarrhea, low red blood cell counts (anemia), lack of energy (fatigue), musculoskeletal pain, bruising, nausea, upper respiratory tract infection, and rash. Healthcare professionals should inform patients of the risk for bleeding (hemorrhage), infections, abnormal heartbeat (atrial fibrillation), development of new cancers (second primary malignancies), metabolic disturbances following treatment (tumor lysis syndrome), and toxic effects on an embryo (embryo-fetal toxicity) associated with the use of Imbruvica. The FDA granted Imbruvica for WM breakthrough therapy designation, priority review, and orphan product designation because the company demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; has potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively. The product's new use is being approved more than two months ahead of its prescription drug user fee goal date of April 17, 2015, the date the FDA was scheduled to complete review of the drug application. Imbruvica is co-marketed by Pharmacyclics, based in Sunnyvale, California, and Janssen Biotech, based in Horsham, Pennsylvania. The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Ibrutinib has been reported to reduce CLL cell chemotaxis towards the chemokines CXCL12 and CXCL13, and inhibit cellular adhesion following stimulation at the B cell receptor. Together, these data are consistent with a mechanistic model whereby ibrutinib blocks BCR signaling, which drives cells into apoptosis and/or disrupts cell migration and adherence to protective tumour microenvironments. In preclinical studies on chronic lymphocytic leukemia (CLL) cells, ibrutinib has been reported to promote apoptosis, inhibit proliferation, and also prevent CLL cells from responding to survival stimuli provided by the microenvironment. Treatment of activated CLL cells with ibrutinib resulted in inhibition of Btk tyrosine phosphorylation and also effectively abrogated downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. Additionally, ibrutinib inhibited proliferation of CLL cells in vitro, effectively blocking survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement and stromal cell contact. In early clinical studies, the activity of ibrutinib has been described to include a rapid reduction in lymphadenopathy accompanied by a transient lymphocytosis, suggesting that the drug might have direct effects on cell homing or migration to factors in tissue microenvironments.
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