Cidofovir Recommended for Approval for CMV Retinitis

On March 15 an FDA advisory panel unanimously recommended approval of cidofovir for injection (Vistide(R), also known as GS 504 intravenous, and by its chemical initials HPMPC), a new drug for treating CMV retinitis. Panel members were concerned about safety and lack of long-term data; but they voted for approval because the drug has proved effective against a condition which urgently needs more treatment options -- effective both in newly diagnosed patients, and in those who had failed other therapies.

Cidofovir, being developed by Gilead Sciences of Foster City, California, is given intravenously (in the trials considered at this meeting); however, it is used only once a week for two weeks, and then every other week after that, so it does not require an implanted catheter (unlike ganciclovir or foscarnet intravenous treatment). Note: Ganciclovir has now been approved by the FDA as an eye implant, and as orally administered capsules, for treating CMV retinitis in certain patients, avoiding the need for a catheter.

The main safety concern with the new drug cidofovir is kidney toxicity; another drug, probenecid, is used to reduce this problem, and hydration is also necessary. In one trial, two thirds of the volunteers had adverse reactions to at least one of the drugs.

The other major concern is that in a laboratory study, cidofovir caused cancers in the mammary glands of female rats. It is not known if this problem occurs in people; however, Gilead reported that no carcinogenicity was found in a 52-week study in primates, and that there were no cases of non-AIDS cancers in over 500 people who have taken the drug, and their AIDS-related cancers were consistent with controls. Very few women have taken cidofovir in trials, so the safety for women is unknown.

Different formulations of cidofovir is also being tested for direct injection into the eye, and as an eyedrop for other infections, and as a topical gel for herpes and for genital warts.

Cidofovir is now available free of charge in the U.S. and Canada through an expanded access program for patients with relapsing disease who have failed or are intolerant to either ganciclovir or foscarnet. For more information about this program, call 800/GILEAD-5.

Note: AIDS TREATMENT NEWS did not attend the March 15 hearing. This article is largely based on coverage in the March 18 issue of BIOCENTURY (a weekly biotechnology newsletter delivered by fax or email, published by BioCentury Publications Inc., in San Carlos, California), and on March 11 and March 15 press releases from Gilead. Also note the coverage March 19 in THE NEW YORK TIMES, of a large initial drop in Gilead's stock price which occurred when a reporter stepped out of the meeting early and headlined old data about the tumors in rats.