Isis Pharmaceuticals Inc. started Phase III trials of its antisensecompound ISIS 2922 to treat cytomegalovirus (CMV)-inducedretinitis in AIDS patients, the Carlsbad, Calif., company saidWednesday.
About 200 patients are expected to be enrolled in two trials, onecomparing ISIS 2922 with Syntex Corp.'s ganciclovir and the otherevaluating the compound in newly diagnosed patients.
About 150 patients are expected in the comparative study. It willevaluate ISIS 2922 in combination with ganciclovir to gancicloviralone. That regimen will be used for three weeks; after that, those inthe first group will be treated only with ISIS 2922, and those in thesecond group will continue ganciclovir treatment.
That study will involve those whose CMV retinitis progressed atleast once while they were being treated with ganciclovir orfoscarnet.
The other trial, with newly diagnosed patients, will compare ISIS2922 therapy with no therapy. That trial, which may involve 50patients, will involve those with retinitis at the periphery of theirretina, giving Isis time to evaluate progression of the disease withoutendangering patients, Stanley Crooke, Isis' president and CEO, toldBioWorld. Patients in the no-treatment group will be given ISIS2922 when their disease progresses.
"We expect some of the data coming from these studies to beevaluable toward the end of 1995," Crooke said. "We know we havea reasonably safe drug, we know we have the dose schedule set andwe have quite a bit of positive data showing the drug is active againstthis disease."
Isis and Tokyo-based Eisai Co. Ltd. entered into a researchagreement on CMV in 1990. The agreement led to a collaboration onISIS 2922 in which the partners are sharing the development costsand will co-promote and market the drug. Eisai has exclusive rightsin Japan, while Isis is accountable for the management anddevelopment of the compound in the U.S. and Europe.
Compound Targets Messentger RNA
The antisense compound acts by inhibiting the function of themessenger RNA. The drug is designed to bind to certain sites on aparticular mRNA of CMV.
In both Phase III studies, 300 micrograms of ISIS 2922 will beadministered by injection into the globe of the eye. It will be injectedonce a week for three weeks, then once every other week. Patientswill be followed for 20 weeks.
"We've already shown [in Phase I/II studies] that it works in thepresence of ganciclovir and its additive," Crooke said. "The dataclearly supported optimism about the drug and initiation of definitivePhase III trials. Now we have to define in a more precise fashion itsvalue in that setting."
The earlier study involved 25 patients with advanced disease in adose-ascending trial. Crooke said significant responses were seen inthe majority of patients, and responses typically occurred within twoweeks. Results were measured by retinal photographs.
"We had very long responses; we had patients who continued inremission for six months," he said. No systemic side effects werereported, he said. Only local inflammation, which was modest andeasily managed.
Isis has two other compounds in the clinic, both of which also areantisense and were developed through the company's own research.ISIS 2105 is in Phase II trials to treat genital warts, as an adjunct tosurgery, caused by human papillomavirus. ISIS 2302, forinflammatory diseases, is in Phase I trials. n
-- Jim Shrine
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