Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

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

To: sam who wrote (3718)	2/3/1998 9:32:00 AM
From: Oliver & Co	Respond to of 6136

Agouron Summarizes VIRACEPT(R) Combination Studies February 3, 1998 09:03 AM LA JOLLA, Calif., Feb. 3 /PRNewswire/ -- Agouron Pharmaceuticals, Inc. AGPH today summarized promising results from clinical trials of VIRACEPT(R) (nelfinavir mesylate) used in combination with other protease inhibitors and other anti-HIV drugs. These results, which are being presented this week at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago, suggest additional treatment options for people taking or considering VIRACEPT in combination with other anti-HIV drugs. VIRACEPT and Fortovase(TM) VIRACEPT was evaluated in combination with Fortovase(TM) (saquinavir soft gel) in 14 patients in a three times daily (TID) dosing regimen that has been ongoing for more than one year. The patients' mean baseline viral load and CD4+ T-cell counts were 39,917 viral copies/mL of plasma and 327 cells/mm3, respectively. After 12 months of treatment, the median CD4+ T-cell count increase was 101 cells and approximately 80% (7/9) of patients had HIV RNA below the limit of detection (<500 copies/mL), with a median viral load reduction of 2.38 log10. Genotypic analyses conducted throughout the study found no occurrence of the mutation D30N (the mutation commonly associated with VIRACEPT). Four patients had the mutations G48V or L90M (the mutations commonly associated with resistance to saquinavir). VIRACEPT and Norvir(TM) VIRACEPT was well tolerated in combination with Norvir(TM) (ritonavir) in 20 patients receiving twice daily (BID) dosing. The patients' mean viral load at baseline was 32,459 viral copies/ml of plasma. Their mean CD4+ T-cell count at baseline was 325 cells/mm3. All patients received 400mg of ritonavir q12h (every 12 hours) with VIRACEPT administered either at 500mg q12h or 750mg q12h. After 12 weeks of therapy, 17 of 19 patients have viral loads below the limit of detection (using the Roche AMPLICOR(TM) HIV assay with a lower limit of detection of 400 copies/mL). Reverse transcriptase inhibitors have been added to the VIRACEPT and Norvir treatment regimens. The most commonly reported side effect for this combination was diarrhea. VIRACEPT and Crixivan(R) The combination of VIRACEPT and Crixivan(R) (indinavir) was evaluated in 21 patients who received twice daily (BID) dosing of 750mg VIRACEPT and 1000mg Crixivan. HIV in plasma fell below the limit of detection by the Roche AMPLICOR assay (<200 copies/mL) in 10 patients receiving this combination for periods between 12 and 32 weeks and, in 6 of these patients, below the limit of detection by an ultrasensitive assay (<50 copies/mL). The mean increase in CD4+ T-cells (infection-fighting cells of the immune system) in the 21 patients after treatment for periods between 12 and 32 weeks was 133 cells/mm3. The most commonly reported side effect for this combination was diarrhea. Currently under evaluation is the twice daily regimen of 1000mg Crixivan plus 1000mg VIRACEPT. A further escalation to 1250mg VIRACEPT BID in the combination is planned. VIRACEPT and Non-Nucleoside Reverse Transcriptase Inhibitors Results from combination studies of VIRACEPT with non-nucleoside reverse transcriptase inhibitors (NNRTIs) also were presented at the conference. Gail Skowron, M.D., Brown University, presented pharmacokinetic and clinical data from a study of 25 patients who were given VIRACEPT in combination with Viramune(R) (nevirapine) + Zerit(R) (d4T or stavudine). Pharmacokinetic studies demonstrated that neither nevirapine nor VIRACEPT altered the plasma concentration of the other, indicating that no adjustments in dosage of either drug is needed in the combination. Five patients discontinued therapy due to adverse events (rash, elevated lipase, and hepatitis/rash). Eight of nine patients who completed 21 weeks of therapy have experienced reductions in viral load below the limit of detection (<400 copies/mL). VIRACEPT was also studied with Sustiva(TM) (efavirenz or DMP266), a NNRTI in development. Pharmacokinetic evaluation showed a 15% increase in VIRACEPT exposure, resulting in no requirement for dosing modification. Efficacy studies are underway to further evaluate this treatment regimen. VIRACEPT and Glaxo Wellcome 1592 VIRACEPT was evaluated in combination with abacavir (Glaxo Wellcome 1592), another antiretroviral drug in development. This combination was found to be safe and well tolerated after 16 weeks of treatment. Seven of nine patients on this combination achieved viral load suppression below the limit of detection at 16 weeks (<400 copies/mL). The median CD4 increase from baseline was approximately 130 cells. The most commonly observed adverse event of moderate or greater severity in clinical trials of VIRACEPT was diarrhea, which was generally controlled with over-the-counter medications. New onset or exacerbation of diabetes mellitus and hyperglycemia, as well as increased bleeding in patients with hemophilia types A and B, have been reported with protease inhibitors. VIRACEPT is indicated for the treatment of HIV infection when antiretroviral therapy is warranted. This indication is based on analyses of surrogate marker changes in patients who received VIRACEPT in combination with nucleoside analogs or alone for up to 24 weeks. At present, there are no results from controlled trials evaluating the effect of therapy with VIRACEPT on clinical progression of HIV infection, such as survival or the incidence of opportunistic infections. Agouron Pharmaceuticals, Inc. is an integrated pharmaceutical company committed to discovery, development, manufacturing, and marketing of small molecule drugs engineered to inactivate proteins that play key roles in cancer, AIDS, and other serious diseases. For further information about Agouron Pharmaceuticals, Inc., or about VIRACEPT, please see Agouron's website at agouron.com or dial toll free 1-888-VIRACEPT (847-2237). To receive full prescribing information for VIRACEPT via fax, dial 1-888-288-9639. WIRES: Full prescribing information for VIRACEPT to follow. VIRACEPT(R) is a registered trademark of Agouron Pharmaceuticals, Inc. Norvir(TM) is a trademark of Abbott Laboratories. AMPLICOR(TM) is a trademark of Roche Laboratories, Inc. Fortovase(TM) is a trademark of Roche Laboratories, Inc. Viramune(R) is a registered trademark of Roxane Laboratories, Inc. Zerit(R) is a registered trademark of Bristol-Myers Squibb Company. Sustiva(TM) is a trademark of DuPont Merck Pharmaceuticals, Inc. SOURCE Agouron Pharmaceuticals, Inc.

To: sam who wrote (3718)	2/3/1998 9:35:00 AM
From: Oliver & Co	Read Replies (1) \| Respond to of 6136

VIRACEPT(R) Produces Durable Anti-HIV Effects For Two Years February 3, 1998 08:31 AM LA JOLLA, Calif., Feb. 3 /PRNewswire/ -- Agouron Pharmaceuticals, Inc. AGPH today announced preliminary results from an ongoing study in which HIV has remained below quantifiable levels in all patients taking VIRACEPT(R) (nelfinavir mesylate) combination therapy for 24 months. These results were presented at the 5th Conference on Retroviruses and Opportunistic Infections in Chicago. Twelve patients in the clinical study carried out at the Aaron Diamond AIDS Research Center received 750mg VIRACEPT TID (three times daily) + 200mg Retrovir(R) (AZT or zidovudine) TID and 150mg Epivir(R) (3TC or lamivudine) BID (twice daily). Prior to treatment, the patients' mean viral load (the amount of HIV in plasma) was 5.32 log10 and their mean baseline CD4+ T-cell count was 258 cells/mm3. One patient was switched to Crixivan(R) (indinavir) + Zerit(R) (d4T or stavudine) + 3TC after four weeks due to intolerance. After 12 weeks of treatment, all patients had HIV RNA levels below the level of quantification (<500 HIV RNA copies/mL with a branch DNA based assay). Three patients experienced virologic failure (two consecutive HIV RNA bDNA assays above the limit of detection) after 7, 15, and 17 months of VIRACEPT combination therapy, respectively, and were switched to d4T + Videx(R) (ddI or didanosine) + Norvir(TM) (ritonavir) + Invirase(R) (saquinavir), with one patient adding Rescriptor(R) (delaviridine) to the combination. After 24 months of treatment, 11 of the 12 patients in the study had viral loads below the level of quantification using the bDNA assay (<500 HIV RNA copies/mL). One patient experienced acute hepatitis B infection while on this regimen which resulted in drug discontinuation and subsequent viral rebound at month 22. All eight patients who have maintained their VIRACEPT treatment for two years remain below the limit of detection (<500 HIV RNA copies/mL); HIV was consistently suppressed below 25 RNA copies/mL (ultrasensitive RT PCR assay) in four of those patients. "The patients who switched to other drug regimens after VIRACEPT failure were susceptible to treatment with other HIV protease inhibitors used in combination with other anti-HIV drugs," said study principal investigator Martin Markowitz, M.D., of the Aaron Diamond AIDS Research Center in New York. "These results suggest that in the event of treatment failure, carefully managed patients may preserve their treatment options over time. The study also suggests the importance of switching treatments early after drug intolerance or demonstrated virologic failure to maintain treatment options for patients." Genotypic testing conducted on virus isolated from the three patients who failed VIRACEPT-containing regimens revealed the following mutations: M184V (commonly associated with 3TC resistance) in all three patients; D30N (commonly associated with VIRACEPT resistance) in two; and L90M in one. No mutations associated with resistance were detected in patients who continued to respond to therapy, despite transient low level increases in HIV RNA as measured by the ultrasensitive RT PCR assay. The most commonly observed adverse event of moderate or greater severity in clinical trials of VIRACEPT was diarrhea, which was generally controlled with over-the-counter medications. New onset or exacerbation of diabetes mellitus and hyperglycemia, as well as increased bleeding in patients with hemophilia types A and B, have been reported with protease inhibitors. VIRACEPT is indicated for the treatment of HIV infection when antiretroviral therapy is warranted. This indication is based on analyses of surrogate marker changes in patients who received VIRACEPT in combination with nucleoside analogs or alone for up to 24 weeks. At present, there are no results from controlled trials evaluating the effect of therapy with VIRACEPT on clinical progression of HIV infection, such as survival or the incidence of opportunistic infections. Agouron Pharmaceuticals, Inc. is an integrated pharmaceutical company committed to discovery, development, manufacturing, and marketing of small molecule drugs engineered to inactivate proteins that play key roles in cancer, AIDS, and other serious diseases. For further information about Agouron Pharmaceuticals, Inc., or about VIRACEPT, please see Agouron's website at agouron.com or dial toll free 1-888-VIRACEPT (847-2237). To receive full prescribing information for VIRACEPT via fax, dial 1-888-288-9639. WIRES: Full prescribing information for VIRACEPT to follow. VIRACEPT(R) is a registered trademark of Agouron Pharmaceuticals, Inc. Retrovir(R) and Epivir(R) are registered trademarks of Glaxo Wellcome Oncology/HIV. Crixivan(R) is a registered trademark of Merck & Co., Inc. Zerit(R) is a registered trademark of Bristol-Myers Squibb Company. Videx(R) is a registered trademark of the Bristol-Myers Squibb Company. Norvir(TM) is a trademark of Abbott Laboratories. Invirase(R) is a registered trademark of Roche Laboratories Inc. Rescriptor(R) is a registered trademark of the Pharmacia & UpJohn Company. SOURCE Agouron Pharmaceuticals, Inc. c 1997 PR Newswire. All rights reserved.