Isis Pharmaceuticals Inc. discontinued development of anantisense compound it had hoped would help in thetreatment of genital warts.

The decision not to pursue further development of ISIS2105 was made after an analysis from a small Phase IIstudy using the antisense compound as an adjuvant tocryotherapy. While the data showed a trend towardreducing wart recurrence, the company decided the trendwas not compelling enough nor the market opportunitylarge enough to warrant continued development.

Isis' stock (NASDAQ:ISIP) fell only 38 cents, to $13.25,showing ISIS 2105 was not one of the main attractions inthe company's robust pipeline.

"One of the strategies we have pursued was to create adiversified portfolio of product opportunities to reducerisk," said Jane Green, investor relations director of theCarlsbad, Calif., company. "This decision was apragmatic one, good for the company and best forshareholders." She said Isis was prepared a year ago tostop development of the compound, but instead decidedto make a small investment to try the 2105 in a secondPhase II study.

"The value has decreased and eliminating it from ourdevelopment pipeline when we have so many moreopportunities that are more promising is a good decisionfor the company, as opposed to a negative," Green said."It's better to make this decision in this relatively earlystage than find out in the middle of a Phase III trial that itisn't worth pursuing."

Isis decided in July 1994 to pursue the compound as asurgical adjuvant after Phase II studies showed ISIS 2105failed to show statistical significance as a primary therapyin treating warts caused by human papillomavirus (HPV).(See BioWorld Today, July 25, 1995, p. 4.)

The trial as an adjuvant to cryotherapy, or freezing ofwarts before their removal, involved nearly 50 patients.The drug was injected directly into the lesion after a wartwas removed. Some of the lesions were treated twice aweek, others three times a week. ISIS 2105 was designedto inhibit production of an HPV protein essential forreplication of wart-causing HPV strains.

"We saw a trend in favor of more frequent dosing,"Green said, "but it wasn't compelling enough." On thebright side, she said, there was no inflammation at theinjection site and the drug was rapidly taken up andcleared. No patients dropped from the study.

Isis' drug candidates are based on antisense technologydesigned to inhibit the function of messenger RNA toprevent production of disease-causing proteins. Amongits corporate collaborators are Ciba-Geigy Ltd., of Basel,Switzerland; Boehringer Ingelheim International GmbH,of Ingelheim, Germany; and Eisai Co. Ltd., of Tokyo.

The company's most-developed product, ISIS 2922, is inPhase III studies to treat cytomegalovirus retinitis inAIDS patients. The studies, in collaboration with Eisai,should be completed by the end of 1996, Green said.

ISIS 2302, an inhibitor of intracellular adhesion molecule(ICAM-1), is being developed with Ingelheim in a dealpotentially worth $100 million. It is in Phase II studies of20 to 40 patients each in renal transplant rejection,rheumatoid arthritis, psoriasis, Crohn's disease andulcerative colitis. Green said the results should startbecoming available in the second half of 1996, at whichtime the decision will be made on the most promisingindications.

Green said Ciba and Isis are on track with theirdevelopment plans, and expect to take two cancercompounds into the clinic in the first quarter. That dealalso is potentially worth $100 million. n

-- Jim Shrine

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