Wednesday, June 21, 2006

More good news for Avastin...PKC theta as a target for autoimmune disease

Todays Headlines from across the DailyUpdates network (for full bulletin click here)
  • Breaking News (from DailyUpdates-Oncology): More good news for Avastin VEGF, a key angiogenic growth factor was discovered by Genentech researchers in 1989 and led to the development of the humanized anti-VEGF antibody, Avastin, beginning in 1997 and in 2004 the FDA first approved Avastin as a first-line treatment for metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy. Broader development of Avastin is being aggressively pursued and Phase III clinical trials are now underway for its potential use in adjuvant and metastatic colorectal, renal cell (kidney), breast, pancreatic, non-small cell lung, prostate and ovarian cancers. Earlier this year Genentech also submitted sBLAs for Avastin plus chemotherapy for first-line treatment of advanced non-small cell lung cancer and breast cancer. Today's featured news item announces announced today that the U.S. Food and Drug Administration (FDA)FDA approval of Avastin in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy for second-line metastatic colorectal cancer. The approval is based on Phase III data from patients who had received previous treatment with irinotecan and 5-FU as initial therapy for metastatic disease or as adjuvant therapy. The study showed that patients who received Avastin plus the 5-FU-based chemotherapy regimen known as FOLFOX4 (oxaliplatin/5-FU/leucovorin) had a 25 percent reduction in the risk of death, the primary endpoint, which is equivalent to a 33 percent improvement in overall survival, compared to patients who received FOLFOX4 alone. The global cancer market is poised for ongoing expansion with sales set to exceed $60bn by 2010. The emergence of novel molecular-targeted treatments will drive a significant proportion of R&D activity and future sales growth in this sector (Optimizing Targeted Treatment in Cancer). Avastin is one of the most successful molecular-targeted treatments with Q1 2006 sales standing at $0.4 billion, double those in Q1 2005; its most recent approval spells good news not only for Genentech, but also for the oncology arena in general [Source: Genentech Release]
  • Featured Journal Article (from DailyUpdates-Neurodegenerative Diseases): PKC theta as a target for autoimmune disease: As expected on June 5th (2006) the FDA recommended reintroduction of the multiple sclerosis therapy, Tysabri back onto the market. The recommendation however restricted Tysabri’s use to patients who have not responded well or cannot tolerate other therapies. Furthermore the recommendations prevent combinations of Tysabri with other multiple sclerosis. These conditions are due in part to the occurrence of multifocal leukoencephalopathy (PML) in some patients receiving Tysabri, an adverse effect that forced Tysabri’s earlier market withdrawal. Today’s edition of DailyUpdates features two important studies relating to this area. In the first [N Engl J Med. 2006 Mar 2;354(9):924-33], researchers from the Institute of Neurology in London publish further information on the incidence of PML. In alignment with Elan/Biogen-IDEC’s announcements, of 3417 patients who had recently received Tysabri while participating in clinical trials, only the three previously reported cases of PML were confirmed. Despite these reassurances analysts still believe the market for Tysabri to fall short of initial expectations thus providing further drivers for the development of novel approaches to the disease. The second paper featured today reports data supporting the targeting of protein kinase C theta (PKC theta) serine/threonine kinase as an approach to multiple sclerosis [J Immunol. 2006 Mar 1;176(5):2872-9]. As discussed in depth in our recent target evaluation report, Potential of T-cells Targeted Therapeutics, numerous T-cell targets represent candidate approaches to multiple sclerosis and one such target is PKC theta. This isoform has been implicated in signaling of T cell activation, proliferation, and cytokine production. Today’s featured study from Lilly reports that PKC theta-deficient mice were completely resistant to the development of clinical experimental autoimmune encephalomyelitis compared with wild-type control mice. This was related to a reduction in IL-17 and LFA-1 expression. This study should prompt the development of PKC theta inhibitors and in this respect it is of note that the crystal structure of the enzyme’s catalytic site has recently been solved [J Biol Chem.2004 Nov 26;279(48):50401-9]


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