Isis Pharmaceuticals announced Tuesday that it has startedPhase II clinical trials on its antisense drug for treating genitalwarts.

The double-blinded trial is designed to determine whether ISIS2105 can delay or prevent wart recurrence following surgicalremoval. Clinicians will administer the antisense compound intothe wound margins at the time of surgery.

Isis (NASDAQ:ISIP) has designed its antisense compound toattack human papillomavirus, which is the cause of mostgenital warts. There are no therapeutics that effectively killthis virus and prevent its recurrence, which is common withina few months, even after a wart has been removed.

Therefore, to be an effective therapeutic, the antisenseoligonucleotide must be relatively durable in vivo, with a longhalf-life. Daniel Kisner, executive vice president of the Carlsbad,Calif., company, told BioWorld that Isis has protected itsantisense oligonucleotides against nuclease digestion by turningthem into sulfur-containing phosphorothioates. While nativeDNA has a half-life of about 30 minutes to one hour in vitro,Kisner explained, phosphorothioates can last from one toseveral days.

As for how they stand up in vivo, "we're just beginning tounderstand how long these things last," Kisner told BioWorld."But we know they're around long enough to have apharmacological effect." Because the compound does stay at thesite of injection for quite a long time, the Phase II trials as theycurrently stand are designed for a single injection of ISIS 2105,Kisner said.

The next step -- and one that is already in Phase I safetystudies -- is to inject the antisense anti-viral directly into thewarts themselves, Kisner told BioWorld. He predicted thatdefinitive Phase II studies for intact warts should start earlynext year. -- Jennifer Van Brunt

(c) 1997 American Health Consultants. All rights reserved.

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