MacroChem Corporation (OTC
Bulletin Board: MACM) today announced results of a Phase 2 clinical trial
involving 37 patients who completed a 48-week, U.S. multi-center,
open-label efficacy and safety study of EcoNail, a topical antifungal
lacquer for the treatment of onychomycosis (nail fungus). The composite
primary efficacy endpoint of the trial was “complete cure” defined as
negative mycology (negative fungal culture and negative KOH) and clear nail
(as determined by expert panel review of clinical photographs). EcoNail is
the company’s patented, topically-applied lacquer which contains the
antifungal econazole and MacroChem’s enhancer SEPA(R).
A protocol-mandated, external expert panel assessed clinical
photographs of 37 onychomycosis patients who completed 48 weeks of EcoNail
treatment. The panel observed that 24 patients (65%) showed evidence of
clinical improvement, defined in the protocol as an increase in uninvolved
(clear) nail area. While none of the 37 patients reached all criteria of
the composite primary endpoint, the consensus judgment of the panel was
that 15 of 37 patients (41%) demonstrated significant (greater than or
equal to 25%) clinical improvement. All patients had fungal culture-proven
nail infections at entry, but after 48 weeks of once-daily treatment with
EcoNail, 100% of patients had cultures that were negative for dermatophyte
growth. Eight of the 37 patients (22%) achieved the secondary endpoint of
negative mycology (negative fugal culture plus negative KOH evaluation) at
48 weeks. The panel observed no signs of local irritation related to the
once-daily EcoNail treatment. During the trial, no patient required
interruption of dosing due to local intolerability. Through 56 weeks of
observation, no cutaneous adverse events were attributed by the
investigators to EcoNail.
The laboratory of Boni Elewski, MD, Professor of Dermatology at the
University of Alabama-Birmingham, performed mycological cultures for this
trial. According to Dr. Elewski, “The proportion of patients with negative
mycology, that is both negative culture and negative KOH, together with the
fact that all the patients had negative cultures at 48 weeks, indicates
that EcoNail has clinically relevant antifungal activity. Consistent with
results from the study’s interim analysis, the final results showed that a
meaningful proportion of patients demonstrated progressive clinical
improvement and reduction of fungal disease burden. Based on the practical
definition of ‘cure’ published in Scher et al in 2007 in the Journal of the
American Academy of Dermatology, it is my opinion upon review of the
clinical photographs that 4 of the 37 (11%) patients achieved a cure.
Minimal onycholysis and no subungual debris in the clinical setting of
negative mycology is for practical purposes cured.” Dr. Elewski added, “If
we exclude 6 patients whose baseline nail involvement in my opinion was too
severe to warrant entry into this trial, then 4 of 31 (13%) would be
considered cured.” The clinical and mycologic findings to date suggest
reason for optimism and further study to fully characterize the benefits of
this new topical treatment in a very common and difficult to cure
condition.”
Michael Goldfarb, MD, Attending Physician, Department of Dermatology at
the University of Michigan, who assisted MacroChem in the development of
the protocol, noted, “As a practicing dermatologist who has limited
treatment options to offer patients with onychomycosis, whether oral or
topical, I was particularly impressed with the lack of skin irritation and
the progressive clinical improvement.” Dr. Goldfarb added, “There are at
least 4 patients in this trial who, if under my care, I would have
considered to have shown resolution of their disease. These factors suggest
that this new topical agent could be an acceptable and valuable treatment
for this typically chronic condition.”
Robert J. DeLuccia, Chairman of MacroChem, stated, “We initiated this
non-registration trial in late 2006 primarily to determine the anti-fungal
efficacy and safety of EcoNail for the treatment of onychomycosis. In
designing our trial protocol, we adopted the clinical endpoints for
defining clinical trial success in this patient population which were
traditionally accepted at that time. Presently, experts in onychomycosis
have developed a new consensus for clinical trial endpoints which, among
other things, more clearly define resolved fungal nail infection and
normal-appearing nail in clinical trials evaluating therapeutic
intervention. There appears to be a greater appreciation today that
onychomycotic nails may have a persistent abnormal appearance even in
patients where antifungal treatment has been completely effective.
Furthermore, long-standing concepts of nail growth have evolved to
recognize that some nails may take up to 78 weeks to fully grow.”
He added, “In view of this new consensus among experts in the medical
community to better define resolution of onychomycosis, the negative
mycology achieved together with the progressively greater clinical
improvement and the number of patients achieving a practical cure together
with the complete lack of local skin irritation seen in our trial, we will
now continue our discussions with potential licensees who have expressed
interest in further development of this promising new topical treatment for
onychomycosis.”
About the EcoNail Phase 2 trial and Onychomycosis
Patients participating in the EcoNail study, which is was conducted
under MacroChem’s U.S. Investigational New Drug application filed with the
FDA, received 48 weeks of treatment at three U.S. sites and included
efficacy assessments using standard criteria of nail appearance and
mycology. This trial was specifically designed, with the assistance of
well-known onychomycosis experts, to address three important objectives: to
assess early signs of efficacy, to maintain robust clinical endpoints in
the full study, and, if successful, to facilitate advancement to Phase 3 as
soon as possible.
Onychomycosis affects 20-30 million people in the United States alone,
including nearly half of those over age 70. Untreated, the disease causes
nails to thicken, resulting in localized pressure-related pain. Topical
treatments currently marketed in the U.S. reportedly succeed in fewer than
12 percent of patients, and existing systemic treatments, which are
effective in less than half of all cases, have known toxicity. Despite the
shortcomings of these existing drugs, sales of treatments for onychomycosis
top approximately $1.5 billion annually worldwide.
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