By Lisa Seachrist
WASHINGTON — The FDA granted approval to Isis Pharmaceuticals Inc.'s Vitravene (fomivirsen), an antisense drug for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients.
Vitravene is the first antisense drug to receive the agency's clearance for marketing. The FDA approved the drug for use in treating patients with AIDS suffering from CMV retinitis who are intolerant of or have contraindications to other treatments for CMV, or who have failed to respond adequately to other therapies.
Daniel Kisner, president and chief operating officer for the Carlsbad, Calif.-based firm, said the approval came "in a very rapid time frame. It's been an enormous effort from [Isis] as well as the FDA to make this happen."
Vitravene is an antisense DNA product designed to prevent CMV from replicating by targeting and binding to the virus's RNA. As an injection directly into the eye, the drug is designed to combat CMV retinitis, a serious and debilitating complication of AIDS that leads to blindness.
The agency approved Vitravene at the recommended dosage of 330 micrograms, to be given as an induction dose on days one and 15, followed by monthly injections.
With the advent of highly active antiretroviral therapy (HAART), including protease inhibitors, the incidence of CMV retinitis has plummeted. As a result, the company could not fully enroll any of the clinical trials conducted with the molecule. However, Isis did administer Vitravene to 330 patients.
Phase IV To Come If CMV Retinitis Escalates
As a result, the Dermatologic and Ophthalmic Drugs Advisory Committee recommended in July that the company conduct a Phase IV post-marketing study to determine Vitravene's role in the CMV armamentarium. (See BioWorld Today, July 23, 1998, p. 1.)
Kisner said Isis has agreed to conduct such studies when the incidence of CMV retinitis hits a level that would allow them to do so. "We all hope the current trend continues and CMV retinitis remains an orphan indication," he said.
However, Kisner and other AIDS experts expect that, as HIV becomes resistant to the new therapies, the incidence of opportunistic infections, including CMV retinitis, is likely to rise.
If that happens, Kisner said, Vitravene could occupy a unique place in battling CMV retinitis, because the drug has a novel method of action. While CMV could ultimately become resistant to the treatment of choice, gancyclovir, Vitravene does not act on DNA polymerase and is likely to still be effective against a drug-resistant strain of CMV.
Mark Augustine, an analyst with Cowen & Co., in Boston, called Vitravene's approval "a psychological positive" for the company. However, he doesn't see Vitravene adding significantly to the company's bottom line.
"This approval isn't going to be the economic watershed event for Isis," Augustine said. "It has never been seen as such."
Augustine pointed to the company's inflammation program as the key to its future. Isis' inhibitor of ICAM-1, known as ISIS 2302, is undergoing a 300-patient pivotal trial to test its ability to quell the intestinal inflammation associated with Crohn's disease. In addition, the company is testing the inflammation modulator for indications in renal transplant rejection, rheumatoid arthritis, and ulcerative colitis. The company is evaluating ISIS 2303 as a topical product for the treatment of psoriasis and as an aerosol for asthma.
"The early results in Crohn's disease have been very promising," Augustine said. "Certainly, we think investors can look at [Isis] with a higher degree of confidence following the Vitravene approval."
Vitravene will be distributed by CIBA Vision Corp., of Atlanta, and will take several weeks to reach pharmacy shelves for dispensing to patients.
Isis stock (NASDAQ:ISIP) closed Thursday at $9.75, up $0.50. *