The Liposome Co., Agouron Pharmaceuticals Inc. andGilead Sciences Inc. were among the companiespresenting positive late-stage clinical data Monday at the35th Interscience Conference on Antimicrobial Agentsand Chemotherapy (ICAAC) in San Francisco.
The Liposome Co., of Princeton, N.J., which already hasthe only lipid-based amphotericin product under FDAreview, presented Phase III results showing its drug,ABLC, had equivalent efficacy with fewer side effectsthan conventional amphotericin B in the treatment ofinvasive candidiasis.
All 231 patients in the U.S. study had confirmedcandidiasis, one of the most common systemic fungalinfections. Both amphotericin B lipid complex (ABLC)and conventional drugs had similar response rates (65 vs.61 percent, respectively) and mycological eradicationrates (88 vs. 87 percent). But the lipid-based drug showedless kidney toxicity.
Baseline serum creatinine levels, where higher levelsrepresent worsened conditions, was significantly reducedin ABLC patients. It doubled in 28 percent of ABLCpatients compared to 47 percent of amphotericin patients(p = 0.007). Also, median number of days before serumcreatinine doubled was 19 for amphotericin B vs. 82 daysfor ABLC (p = 0.028).
Last May, The Liposome Co. filed a new drug application(NDA) for ABLC seeking approval in the treatment ofrefractory aspergillosis. The company is not disclosing itsfiling plans in candidiasis, a larger indication, but it doesnot expect to take action before the FDA makes adecision on the initial filing, said Brooks Boveroux, thecompany's vice president, finance, and chief financialofficer.
The Liposome Co. _ as well as competitors NeXstarPharmaceuticals Inc., of Boulder, Colo., and SequusPharmaceuticals Inc., of Menlo Park, Calif. _ haveliposome- or lipid-based amphotericin B products on themarket in Europe.
The Liposome Co.'s stock (NASDAQ:LIPO) gained 38cents Monday to close at $15.50.
Agouron's Viracept Reduces HIV Levels
Agouron presented data from its 30-patient U.S. pilotPhase II trial of AG1343, now called Viracept, which is asynthetic compound designed to inhibit HIV protease.
Twice-daily doses of 500 mg, 600 mg and 700 mg forfour weeks resulted in average maximum reductions ofHIV in blood of 90, 94 and 93 percent, respectively, andin reduced levels of HIV at the end of the study. The LaJolla, Calif., company said significant increases were seenin CD4+ cells, improvements in some HIV-relatedconditions were observed, and the drug was safe and welltolerated.
The pilot Phase II study and one concluded earlier in theU.K. essentially wrap up the Phase II portion ofViracept's development. Peter Johnson, Agouron'spresident and CEO, said additional work might be doneto tighten up dosing and scheduling, but that a pivotalPhase II/III program is expected to start by the end of theyear.
In general, Johnson said, the pivotal studies will includeabout 1,000 patients spread across three or four studies,with at least some of the emphasis on combinationtherapy.
Johnson said the U.S. study "tells us that Agouron'sprotease inhibitor is very active as an anti-retroviralagent, and its safety profile suggests it will be anexcellent component in combination therapy."
Agouron's stock (NASDAQ:AGPH), which has beenvolatile (but mostly higher) of late, gained $1 Monday toclose at $29.
Gilead's Vistide Delays Progression To Retinitis
The Foster City, Calif., company said interim data from apivotal study of Vistide (cidofovir intravenous) showedthe nucleoside analogue delayed progression time toretinitis in patients with relapsing cytomegalovirus(CMV) retinitis, an AIDS-related opportunistic infection.
The data were taken from an analysis of the first 60patients in a 126-patient dose-comparison study. Thepatients, who had progressed despite a median of fourcourses of other therapies, were randomized to one of twoVistide maintenance regimens. Median time toprogression in the higher-dose group (5 mg/kg) was 115days; in the other group (3 mg/kg) it was 49 days.
Earlier this year Gilead released data from its first pivotalCMV retinitis study, which was conducted in previouslyuntreated or newly diagnosed patients. Time toprogression was delayed 120 days in that study.
Lana Lauher, manager, corporate communications forGilead, said median time to progression for two historicalgroups was 22 and 35 days, respectively.
"We see all of these data as very positive," Lauher said."The NDA is very much on track and we hope to filewithin the next several weeks." She said data from the126-patient study will supplement the initial data in thefiling, and the company intends to seek approval ofVistide for both relapsing and newly diagnosed patients.
Gilead has all rights to the product for CMV retinitis. Itsstock (NASDAQ:GILD) fell $1.38 Monday to close at$22.75.
In Other Conference News . . .
* Aronex Pharmaceuticals Inc., of The Woodlands,Texas, said results of a Phase I study of liposomalnystatin for systemic fungal infections showed the drugwas well tolerated and adverse events were notsubstantial. The study involved 32 neutropenic cancerpatients. Enrollment is ongoing in a Phase II study of thedrug, NystatinLF, in non-neutropenic patients withproven candidemia.
* Data were presented showing that Philadelphia-basedSmithKline Beecham's Augmentin (amoxicillin/cla-vulanate potassium) demonstrated greater in vitro activityagainst drug-resistant Streptococcus pneumoniae thanpenicillin and other antibiotics, according to a studysponsored by SmithKline Beecham. n
-- Jim Shrine
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