CMV, RS-79070: Community Concern As Major Drug's Development Suspended

Last week AIDS treatment activists learned that plans forfuture Phase III trials of RS-79070, an oral prodrug ofganciclovir, had been suspended by Hoffmann-La Roche,apparently due to concern that there are no longer enough newcases of CMV retinitis to justify the expense of continuing development. A smaller phase II trial, which is still recruiting, will continue (see announcement below). The decision was made at Roche offices in Basel.

RS-79070 is a chemical relative of ganciclovir which can bereadily absorbed orally, and then is changed to ganciclovirin the bloodstream. It provides much higher blood levels of ganciclovir than the currently approved oral drug, which is poorly absorbed. Because of its lower efficacy, the oral ganciclovir which is now available cannot be used for induction (the initial high-dose treatment of CMV retinitis),and is controversial for maintenance (long-term treatment of active CMV disease after induction) and prophylaxis (prevention of CMV disease in persons who are at risk).

RS-79070 may replace intravenous treatments or ocular implants for CMV disease, with a pill which is taken once aday (twice a day for the first three weeks of treatment for the induction phase). Because it delivers ganciclovir to the body, it will have the same basic side effects of that drug.Unfortunately, current drug-development rules require large and expensive phase III trials before RS-79070 can be marketed -- even though (1) this drug serves only as a better delivery vehicle for supplying ganciclovir orally, (2) a less effective oral ganciclovir is already approved, and (3) the smaller phase II trial now recruiting will show whether or not RS-79070 is comparable to intravenous ganciclovir for induction treatment of CMV retinitis.

Project Inform, in San Francisco, which first learned of the decision to suspend development of the large trials required for marketing, is deeply concerned because it has been hearing quite good anecdotal reports about RS-79070 from physicians and patients -- and also because of reports that the number of new cases of CMV retinitis may be starting to rise again, due to more treatment failures after longer-term use of the new combination anti-HIV regimens. GMHC (Gay Men's Health Crisis, in New York) is organizing a letter of protest to Roche.

The phase II trial described below will continue -- and will provide data which might justify reviving the plans for phase III trials which could lead to general availability of RS-79070.