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Biotech / Medical : CYPB - Cypress BioScience -- Ignore unavailable to you. Want to Upgrade?

To: Jay Lowe who wrote (274)	6/3/1998 11:55:00 AM
From: dwight martin	Read Replies (1) \| Respond to of 586

Yeah, I'm also curious about the claimed virtue of the column in "severe, drug-resistant cases." While I am not known for medical knowledge, it seems to me that if the less-severe manifestation of the disease is caused in whole or part by the same circulating factors causing the severe form, the column's clearing action should also work in those less severe cases. And the column treatment lasts for a long time, with no side effects . . . ? What is the general thread sentiment on the reverse split and its likely effect on stock price this summer?

To: Jay Lowe who wrote (274)	6/5/1998 4:52:00 PM
From: muddphudd	Respond to of 586

A little on Immunex's Enbrel: Tumor necrosis factor (TNF) is a pro-inflammatory cytokine involved in the pathogenesis of Rheumatoid Arthritis. TNF induces release of matrix mettaloproteases from neutrophils, fibroblasts, and chondrocytes; induces the expression of endothelial adhesion molecules involved in the migration of leukocytes to extravascular site of inflammation; and stimulates the release of other proinflammatory cytokines. There are two distinct cell-surface TNF receptors (TNFRs), designated p55 and p75. Soluble, truncated versions of membrane TNFRs, consisting of only the extracellular, ligand-binding domain, are present in body fluids and are thought to be involved in regulating TNF activity. What Immunex did was to design a recombinant human TNFR p75-Fc fusion protein (TNFR:Fc). This molecule contains the soluble portion of TNFR p75 linked to the Fc portion of human IgG1. What this molecule does is act like a decoy to the endogenous TNF. It binds up the TNF before it can interact with the cellular receptor, thereby preventing the initiation of the events that lead to inflammation. All the patients in the phase III study had been unsuccessfully treated with between one and four of the following disease-modifying antirheumatic drugs: hydroxychloroquine, oral or injectable gold, methotrexate, azathioprine, penicillamine, and sulfasalazine. There were four study groups: Placebo, 0.25 mg TNFR:Fc, 2 mg TNFR:Fc, or 16 mg TNFR:Fc. The study drug or placebo was injected subcutaneously twice weekly for 3 months. The results showed a dose-dependent improvement of symptoms (total # swollen joints, tender joints) and secondary end-points (pain, duration of morning stiffness, quality of life, sedimentation rate, C-reactive protein level, and physician's and patient's global assessment) compared to placebo. TNFR:Fc was well tolerated; no dose-limiting toxic effects were observed. Adverse-effects were limited to injection-site reactions and mild upper respiratory tract symptoms (cough, runny nose, sore throat). Importantly, no hematological abnormalities were noted during the study. Also, they did not detected the emerges of autoimmune antibodies against the TNFR:Fc fusion protein. This is an important point because usually a major concern of monoclonal-antibody therapy is the potential for patients to form antibodies that neutralize the therapeutic agent. Interestingly, though not surprisingly, cessation of therapy was associated with an increase in disease activity, suggesting that continued administration is necessary for sustained effect. Most of the above was paraphrased from the New England Journal of Medicine article that appeared in July, 1997 (NEJM 337, page 141). There is also a good editorial on page 195. I just heard on CNBC that Immunex's Enbrel may be a 1 billion dollar blockbuster according to some analysts. They are currently working on an oral form of the therapy. The way I see it, Enbrel is a good short-term therapy. I doubt it will work as a long term treatment since it requires non-stop medication and that will cost mucho dinero $$$. Also, though they did not find any auto-antibodies during the short 3-month trial, there are reports of patients developing anti-DNA, anti-ANA antibodies leading to frank Lupus in other trials using anti-TNF therapies. I would also be curious whether long-term use of TNFR:Fc could lead to kidney problems. The study above found that the levels of TNF are not reduced with the TNFR:Fc therapy, rather the TNF is neutralized and is not biologically available. Such circulating antibody:antigen complexes can get sequestered in the kindeys (like in other autoimmune diseases) and cause some degree of kidney failure. Time will tell, I guess. Well, that's it for now. I hope this helps. I think that the Prosorba column is not in direct competition with Enbrel. In fact, it has the advantage that after 12 (or fewer) exchanges the symptom-free period last for a long time. Cypress hopes to make the column available at a discount of what they charge now for ITP. These 2 factors (symptom-free period after treatment and $$$) may help Prosorba penetrate the market. I guess patients may have the choice of a bi-weekly injection for the rest of their life or a few plasmapheresis sessions and a drug-free, symptom-free interval....or maybe both.