Isis Pharmaceuticals Inc. earned a $10 million milestone paymentfrom Boehringer Ingelheim GmbH following successful completionof a Phase IIa trial, which yielded the first data demonstrating thepotential effectiveness of Isis' antisense compounds administeredsystemically in humans against a severe disease.
"This is a very important milestone for our technology," said StanleyCrooke, chairman and CEO of San Diego-based Isis.
Another antisense drug, administered to the eye for AIDS-relatedcytomegalovirus retinitis, has demonstrated efficacy and hasprogressed to Phase III trials. And studies in multiple animal modelsof human diseases have shown the potential effectiveness of antisensecompounds.
But the trial of ISIS 2302 in Crohn's disease, Crooke observed, "isthe first demonstration of antisense's efficacy in humans whenadministered systemically for a severely disabling disorder."
Antisense compounds are oligonucleotides designed to block thefunction of messenger RNA and to prevent production of disease-causing proteins. ISIS 2302 targets intercellular adhesion molecule 1,a protein whose over-expression is linked to inflammatory disorders.Crohn's disease is an inflammatory bowel disorder.
In addition to triggering the first milestone payment from BoehringerIngelheim, of Ingelheim, Germany, the pharmaceutical company andIsis will move ISIS 2302 into a pivotal Phase IIb study in 300patients with Crohn's disease.
The milestone payment was made in the form of an equityinvestment. Boehringer Ingelheim purchased about 409,000 Isisshares at $24.47 per share, which was a 46 percent premium to thestock's (NASDAQ:ISIP) $16.75 closing price Monday.
Isis ended Tuesday up 10 percent to $18.375, a $1.625 gain.
ISIS 2302 is the lead antisense compound in Isis's potential $100million collaboration with Boehringer Ingelheim focusing on celladhesion molecules, which are involved in movement of white bloodcells through blood vessel walls to inflamed tissues.
The compound is under evaluation in four other Phase IIa trials forrenal transplant rejection, rheumatoid arthritis, psoriasis andulcerative colitis. Data from those studies is expected over the nextseveral months.
Crooke said the two companies anticipated going forward into pivotalstudies of ISIS 2302 in two indications. Crohn's disease is the first.The second indication selected also will trigger another $10 millionequity investment by Boehringer Ingelheim.
The pivotal Phase IIb trial in Crohn's disease is expected to beginduring the first quarter of 1997 and will take about 18 months tocomplete.
However an analysis half-way through the placebo-controlled trialwill be conducted, Crooke said, and if the interim data is positive, asecond Phase IIb trial will begin. Results of the two pivotal studies,he said, will be sufficient for application to the FDA for marketapproval.
Details of the Phase IIa trial results in Crohn's disease are expectedto be presented in February at a conference on gastrointestinaldisorders.
The placebo-controlled study, involving 20 patients, was designed todemonstrate safety and generate early efficacy data. A Phase I safetytrial in healthy volunteers in 1995 showed the drug was well-tolerated.
Crooke said the efficacy findings were evaluations based on aCrohn's disease activity index, which assess signs and symptoms ofthe disease, and colonoscopies performed on the patients to judge thecondition of their colons.
The Phase IIa study was not designed to yield statistically significantefficacy findings, but Crooke noted the results were encouragingenough for Boehringer Ingelheim to commit to the larger Phase IIbpivotal studies.
In its collaboration with Boehringer Ingelheim, Isis received a $28.5million equity investment up front when the agreement was signed inMarch 1995. That stock purchase, at $15 per share, also representeda significant premium to Isis' trading price.
Boehringer Ingelheim also provided Isis with $8.3 million in October1996 from a $40 million line of credit included in the partnershipdeal. Isis can repay those funds in cash or stock.
Isis' lead antisense compound, ISIS 2922, is under evaluation inPhase III trials for AIDS-related CMV retinitis in a collaborationwith Tokyo-based Eisai Co. Ltd. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.