Novel Antifungal Agent Demonstrates Activity Against Coccidioidomycosis, a Potentially Deadly Fungal Disease

KENILWORTH, N.J. -- Schering-Plough Corporation today reported results from a case series evaluating the efficacy and safety of NOXAFIL (posaconazole oral suspension) for the treatment of coccidioidomycosis, a potentially deadly fungal disease, after standard antifungal therapies have failed. In this study, six patients with coccidioidomycosis who had failed conventional therapies received oral NOXAFIL. All six patients initially received benefit from the drug, and five were long-term successes during the follow-up period.

Gregory Anstead, MD, presented details on the treatment experience of one hospital (University of Texas Health Science Center at San Antonio) that participated in a multicenter clinical trial. The data were presented at the 41st annual meeting of the Infectious Diseases Society of America (IDSA) in San Diego, Calif., on October 10.

"Coccidioidomycosis starts when people inhale the fungal spores that are present in the soil. This can lead to a flu-like illness, which, for most people, will resolve on its own," said Anstead, staff physician, South Texas Veterans Health Care System. "However, some people, especially those with defects in their immune system, can get disseminated coccidioidomycosis, which can be very difficult to treat. Many of these patients do not respond to the currently available antifungal drugs or experience unacceptable side effects. We are hopeful that NOXAFIL will be a potent new weapon for the treatment of this destructive and deadly fungal disease," he said.

NOXAFIL is a novel oral, broad-spectrum antifungal agent discovered by Schering-Plough Research Institute (SPRI) that is being developed for the treatment of life-threatening invasive fungal infections that are refractory to currently available antifungal treatments.

In the study, oral NOXAFIL was administered under Phase III treatment protocols sponsored by SPRI and demonstrated the following results:

-- NOXAFIL treatment appeared to benefit six patients who had been

infected with Coccidioides immitis, an endemic fungal infection

(coccidioidomycosis, also known as "cocci") commonly encountered in

the southwestern United States, California and Mexico.

-- Prior to enrollment in the NOXAFIL studies, all six patients had

failed currently available therapies (with five of the six failing

more than one), including fluconazole or amphotericin B (including

lipid formulations), which were either not effective or had produced

undesirable side effects. In this group of patients, activity was

seen in all six patients, with long-term benefit seen in four, and

with a fifth patient maintaining stability of their disease.

-- NOXAFIL produced rapid and significant clinical improvements, often

with initial responses noted within one month. Long-term (>1 year)

treatment is usually required to control this disease.

-- NOXAFIL appeared to be well tolerated during long-term use in these

patients, with most patients receiving NOXAFIL for 10 months and one

patient receiving NOXAFIL for more than one year. Most reported

adverse events were mild to moderate in severity.

-- The majority of patients treated with NOXAFIL in this trial did not

develop breakthrough infections.

Coccidioidomycosis is typically an indolent disease, which may be difficult to treat in immunocompromised patients or in its advanced stages. Coccidioidomycosis can cause serious or life-threatening infections of the lungs, bone, skin and soft tissues, central nervous system or disseminated disease involving multiple sites. Success rates are considered to be unacceptably poor with currently available therapies.

While Coccidioides is endemic to the desert regions of Arizona and California, New Mexico, Texas, the San Joaquin valley in California, and semi-arid regions of Central and South America, including Mexico, it can be diagnosed in people who have recently moved to these areas or who have traveled to these areas and developed symptoms weeks or months after returning home.

The Centers for Disease Control and Prevention (CDC) has investigated numerous outbreaks of coccidioidomycosis occurring in groups traveling to these areas for vacation or other events. In Arizona, the number of reported cases of coccidioidomycosis increased by 46 percent between 2001 (n = 2,301 reported cases) and 2002 (n = 3,351 reported cases).

While critically ill and immunocompromised patients are typically most susceptible to serious fungal infections, Coccidioides affects otherwise healthy people as well. Risk factors for developing symptomatic or serious coccidioidomycosis include diabetes mellitus, smoking, pregnancy and advanced age. African Americans or Latinos may be more susceptible to serious infections with this fungus for reasons that are not completely understood.

Source: Schering-Plough Corporation