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Biotech / Medical : Vertex Pharmaceuticals (VRTX) -- Ignore unavailable to you. Want to Upgrade?

To: quidditch who wrote (590)	4/30/2002 2:22:17 AM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 1169

From BC (Thanks Rudy): Gita must be the only one who saw PIII planning coming! AND DOSE WILl BE ... ???? <<VRTX and AVE did report that more than 40% of patients given the higher dose of pralnacasan achieved ACR20 at 12 weeks of treatment. Alam told BioCentury that the p value was not significant, though the companies have not disclosed the percentage of placebo patients who achieved ACR20.>> The niche for Vertex’s RA agent Vertex Pharmaceuticals Inc. and partner Aventis S.A. are planning Phase III trials of VRTX’s pralnacasan in rheumatoid arthritis, despite the fact that ACR20 scores in a Phase II study released last week were less robust than for several other RA products on the market or in late development. The partners believe that the product’s oral dosing should make it attractive to patients with milder forms of the disease. VRTX (Cambridge, Mass.) and AVE (Strasbourg, France) reported a trend towards a dose response in patients achieving ACR20 in RA patients given pralnacasan, an oral inhibitor of interleukin-1 beta converting enzyme (ICE), in a placebo-con-trolled Phase II trial. In addition, patients given pralnacasan had significant improvements in markers of inflammation such as C-reactive protein levels and erythrocyte sedimentation rate. Though the dose response was not significant, John Alam, senior vice president of drug evaluation and approval at VRTX, noted that the 285 patients enrolled in the trial were very heterogeneous. Patients were given either placebo or one of two doses of pralnacasan in addition to background therapy. The latter could include no additional therapy, steroids, or one or more DMARDs. VRTX and AVE did report that more than 40% of patients given the higher dose of pralnacasan achieved ACR20 at 12 weeks of treatment. Alam told BioCentury that the p value was not significant, though the companies have not disclosed the percentage of placebo patients who achieved ACR20. Comparison data available from marketed products shows an ACR20 response rate of 71% after 24 weeks in a Phase II/III trial in patients given both Enbrel etanercept from Immunex Corp. (IMNX, Seattle, Wash.) and methotrexate. In a Phase III trial of Remicade infliximab from Johnson & Johnson (JNJ, New Brunswick, N.J.), 50-58% of patients given Remicade plus methotrexate for 30 weeks achieved ACR20 (see BioCentury, Dec. 6, 1999 & Nov. 16, 1998). Placebo plus methotrexate ACR20 response rates in those trials were 27% and 20% respectively. Similarly, data from a Phase II trial of D2E7, an anti-TNF-alpha antibody from Cambridge Antibody Technology plc (LSE:CAT; CATG, London, U.K.) and partner Abbott Laborato-ries (ABT, Abbott Park, Ill.), showed an ACR20 response rate of 66% in patients given 40 mg doses of D2E7 plus methotrexate for 24 weeks. CAT and ABT filed a BLA and MAA for D2E7 to treat RA earlier this year (see BioCentury, June 18, 2001 & April 15, 2002). Finally, Kineret anakinra, an IL-1 receptor antagonist from Amgen Inc. (AMGN, Thousand Oaks, Calif.), given in combination with methotrexate gave an ACR20 response of 38% at 24 weeks, compared to 22% in placebo plus methotrexate patients (see BioCentury, Aug. 20, 2001). Pralnacasan inhibits ICE, which is responsible for production of IL-1beta and IL-18. Thus Kineret’s approval provides validation that modulation of the IL-1 pathway can provide clinical benefit in RA patients. In addition, while the RA space is increasingly populated with injectable products, pralnacasan is an oral formulation, which would give it an advantage in ease of dosing. In addition, Alam told BioCentury that if pralnacasan shows a good side effect profile, it may be better suited to treat patients with milder forms of disease. Additional data from the trial are ex-pected to be presented at AVE’s R&D day on June 18 and 19 in London and New York. – Gita Kumar