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Biotech / Medical : VPHM - Viropharma Inc -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (275)	8/29/1999 12:55:00 PM
From: scaram(o)uche	Respond to of 2557

Session: Respiratory and Enteroviruses (with minilecture) Location: 305 Session Date: Tuesday, 9/28/99 Session Time: 2:00 pm - 4:30 pm Presentation Time: 4:15 pm - 4:30 pm Pleconaril Is Effective for Enteroviral Meningitis in Adolescents and Adults: a Randomized Placebo-Controlled Multicenter Trial S.D. Shafran1, W. Halota2, D. Gilbert3, J. Bernstein4, H. Meislin5, M. Reiss6, ;. The Collaborative Meningitis Group7 1Univ. of Alberta: Edmonton, AB, Canada; 2Univ. Sch. of Med.: Bydgoszcz, Poland; 3Providence Portland Med. Ctr.: Portland, OR; 4Wright State Sch. of Med.: Dayton, OH; 5Univ. of Arizona: Tucson, AZ; 6Beta Res.: Hinsdale, IL; 7ViroPharma Inc.: Exton, PA Background: Currently there are no treatments available for enteroviral meningitis, the most common infection of the CNS. Pleconaril is a first-of-a-kind orally bioavailable antiviral agent that selectively inhibits picornavirus replication by preventing viral attachment and uncoating. Pleconaril has previously demonstrated activity in enteroviral meningitis in children. In this study, pleconaril was evaluated in adolescent and adult patients with enteroviral meningitis. Methods: This multicenter, double-blind, placebo-controlled trial evaluated pleconaril 200 mg po TID for 7 days in patients aged 14 to 65 years with PCR-confirmed enteroviral meningitis in whom severe headache was present for less than 48 hours. Results: 130 patients were enrolled into the study (mean age 30 y: equally distributed between males and females). Pleconaril-treated patients experienced a more rapid resolution of headache (median duration 2 days shorter; p=0.04) and resolution of symptoms of meningitis (median duration 2 days shorter). Pleconaril-treated patients returned to work or school 2 days earlier (p=0.045) than placebo-treated patients. Adverse events were less common in pleconaril-treated than in placebo-treated patients (26% vs. 39%, respectively, P=NS). Conclusion: Pleconaril is a well-tolerated and systemically effective treatment for enteroviral meningitis in adolescents and adults. Further clinical studies of pleconaril are warranted.

To: scaram(o)uche who wrote (275)	8/29/1999 1:13:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 2557

Session: Respiratory Viral Infections Location: Exhibit Hall Session Date: Sunday, 9/26/99 Session Time: 11:00 am - 12:30 pm Comparative In Vitro Antirhinoviral Activity of AG7088 and Pleconaril L. Kaiser1, C. Crump1, A.K. Patick2, L.S. Zalman2, F.G. Hayden1 1Univ. of Virginia Sch. of Med.: Charlottesville, VA; 2Agouron Pharmaceuticals, Inc.: San Diego, CA Background: The 3C protease inhibitor AG7088 and the capsid-binding inhibitor pleconaril are anti-picornaviral agents in clinical development. Our aim was to evaluate the in vitro activity of these two drugs against both laboratory and primary human rhinovirus (HRV) isolates. Methods: The 50% effective concentrations (EC50) of AG7088 and pleconaril were determined in Ohio HeLa-I cell monolayers by a cytopathic effect (CPE) inhibition assay read either microscopically or spectrophotometrically after staining with 0.4% crystal violet. First passage HRV field isolates (isolated from nasal washes from children and adults with natural colds over a 4 year time period) and 4 representative HRV serotypes (39, 16, 14 and Hanks) were tested at three concentrations (1.0, 0.1 or 0.01 mg/ml). Results: For field isolates (n=15), the EC50 value determined by the CPE assay ranged from <0.01 to 0.05 µg/ml for AG7088 and from <0.01 to >1 µg/ml for pleconaril. AG7088 inhibited all field isolates tested whereas pleconaril inhibited 13 of 15 isolates tested. The EC50 values obtained using either microscopic or spetrophotometric methods were similar (r=0.98 for AG7088 and r=0.99 for pleconaril). The median EC50 value for evaluable isolates (EC50 value ³ 0.01 and £ 1 µg/ml) determined microscopically was 0.018 mg/ml (0.030 µM) (range, 0.01 to 0.05 µg/ml) for AG7088 compared to 0.082 mg/ml (0.214 µM) (range, 0.01 to 0.215 µg/ml) for pleconaril (p<0.05). Likewise, the median EC50 value determined spectrophotometrically for evaluable isolates was 0.017 mg/ml (0.028 µM) (range, 0.01 to 0.033 µg/ml) for AG7088 compared to 0.038 mg/ml (0.100 µM) (range, 0.014 to 0.2 µg/ml) for pleconaril (p<0.05). For 4 defined serotypes, no significant differences in antiviral activity were observed between the drugs. The median EC50 value determined by microscopic and spectrophotometric methods was 0.035 mg/ml (0.058 µM) (range, 0.017 to 0.05 mg/ml) and 0.02 mg/ml (0.033 µM) (range 0.02 to 0.12 mg/ml), respectively, for AG7088, compared to 0.06 mg/ml (0.157 µM) (range, 0.011 to 0.09, mg/ml) and 0.051 mg/ml (0.134 µM) (range, 0.02 to 0.12 mg/ml), respectively, for pleconaril. Conclusions: Although under in vitro conditions AG7088 and pleconaril have demonstrated comparable antiviral activity against 4 defined HRV serotypes, more potent activity was demonstrated for AG7088 compared to pleconaril against HRV clinical isolates.

To: scaram(o)uche who wrote (275)	8/29/1999 1:16:00 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 2557

Session: New and Emerging Therapies Location: 103/104 Session Date: Monday, 9/27/99 Session Time: 2:00 pm - 4:30 pm Presentation Time: 2:30 pm - 3:00 pm Pleconaril for Enteroviral Infections H.A. Rotbart Univ. of Colorado: Denver, CO The picornaviruses, particularly the enteroviruses (EVs) and rhinoviruses, are among the most common and most important viral pathogens of humans. In the U.S. alone, the EVs are estimated to cause 5 to 10 million symptomatic infections annually, including meningitis, encephalitis, poliomyelitis, myocarditis, hemorrhagic conjunctivitis, hand foot-mouth syndrome, pleurodynia, severe neonatal disease, and non-specific febrile illnesses. Pleconaril (ViroPharma, Inc; Exton, PA) inhibits EV and rhinovirus replication by inhibiting viral uncoating and blocking viral attachment to host cell receptors; the drug is highly orally-bioavailable. A favorable safety profile is attributed to the metabolic stability and viral-specific nature of the mechanism of action. The compound has been studied in a variety of clinical trials including an EV challenge study in volunteers; compassionate use in more than 40 patients with life-threatening EV infections, and three (two adult, one pediatric) double-blinded, placebo-controlled studies in meningitis. Evidence for a beneficial effect of pleconaril was seen in all of these studies, the data for which will be presented. Studies of pleconaril in other diseases, including viral respiratory infection and severe neonatal EV disease, are underway.