Contact: Kyra Lindemann
Office: 215/652-6931
Merck Research Laboratories Presents Preliminary Phase II
Efficacy Data with MK-991, Merck's Echinocandin Antifungal
Toronto, Ontario, Canada, October 1, 1997 - Preliminary results from a
Phase II study with Merck's echinocandin antifungal, MK-991 (formerly
known as L-743,872), showed efficacy in 85% of patients with Candida
esophagitis. The data were presented today at the 37th Interscience
Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting
in Toronto, Ontario, Canada.
According to Carole Sable, M.D., Associate Director, Clinical Research,
Merck Research Laboratories, who presented the study results, *these
data are preliminary and support further study to determine the efficacy
of the new class of echinocandin antifungals represented by MK-991.*
In the double-blind study, 128 patients with endoscopically documented
Candida esophagitis were randomized to intravenous therapy with
MK-991 at 50 mg/day, MK-991 at 70mg/day or Amphotericin B (AMB) at
0.5 mg/kg/day for 14 days. The majority of study patients were
HIV-infected (78% on MK-991 and 82% on AMB) and 46% of patients on
MK-991 and 41% on AMB had CD4 counts less than 50 cells/mm3.
Efficacy was assessed by the clinical resolution of symptoms and the
reduction in endoscopic lesions after 14 days of therapy.
85.1% (63 out of 74) of patients in the combined MK-991 group (38 of 46
at 50 mg and 25 of 28 at 70 mg) responded to treatment compared to
66.7% (36 out of 54) of patients in the AMB group. Treatment with
MK-991 was generally well-tolerated and no serious drug-related
adverse events were reported in patients receiving MK-991. Just over
4% of patients (3 out of 74) on MK-991 discontinued the study due to a
drug-related adverse event as compared to 22.2% (12 out of 54)
receiving AMB. The three adverse events listed by the investigator
included thrombocytopenia, elevated serum creatinine, and rash.
Fungal infections have emerged as a major medical problem. Infections
due to Candida species today account for approximately 80% of all major
systemic fungal infections. The rate of disseminated Candida infections
in hospitalized patients increased nearly five-fold in the decade ending in
1989. Candida is now the fourth most common organism found in
bloodstream infections and Candida species are also the most common
cause of fungal infections in immunocompromised patients. Fungal
infections caused by Aspergillus is a frequent cause of infection-related
mortality in transplant and immunocompromised patients.
Resistance to the commonly used azole antifungals is developing and
amphotericin B therapy is associated with acute and chronic toxicities,
including renal toxicity.
*MK-991 is the first in a new class of echinocandins that appear to block
the synthesis of an essential component of the fungal cell wall (not
present in human cells) resulting in fungal cell death. This is in contrast
to fungistatic agents - such as the azoles - that stop the organism from
growing but do not kill it. The clinical significance of this difference
warrants further study,* explained Dr. Sable.
In this Phase II study, MK-991 was administered once-daily as an
intravenous formulation, and was generally well-tolerated. MK-991 is an
investigational antimicrobial agent that has shown antifungal activity
against Candida species and Aspergillus species and efficacy against the
cyst form of Pneumocystis carinii in preclinical studies (first reported at
the 36th ICAAC in 1996). The compound is being developed by Merck to
see if it is effective in the treatment of serious, systemic fungal
infections, including those in immunocompromised patients.
Merck & Co., Inc. is a leading research driven pharmaceutical products
and services company. Merck discovers, develops, manufacturers and
markets a broad range of innovative products to improve human health.
###
RSS