STOCKHOLM, Jan. 22, 2020 /PRNewswire/ -- Moberg Pharma AB
(OMX: MOB) has now completed the expert evaluation of the results
from the North American Phase 3-study. The analysis conducted with
key opinion leaders (KOLs) has confirmed the validity of the data
presented in December 2019 and
increased the understanding of the study outcomes. Key conclusions
include: i) MOB-015 delivers a very high mycological cure rate that
compares favorably to oral antifungal drugs with the added
advantage of an earlier onset of action; ii) Confirmation that the
proprietary vehicle technology increases the hydration and
permeability of the nail plate enabling efficient terbinafine
delivery, however it also confounds the assessment of
clinical cure and complete cure and iii) A likely solution to the
problem - a shorter dosing regimen with the potential to deliver
superior complete cure rates.
In December 2019, the topline
results were presented from the first of two clinical studies in
the Phase 3 program for MOB-015, meeting the primary endpoint.
Mycological cure (eradicating the fungal infection) was achieved in
70 percent of the patients, which is substantially higher than
reported for other topical treatments (30-54 percent). Furthermore,
83 percent of the patients reported visible nail improvement by the
first follow-up visit. However, despite the strong mycological cure
and rapid visible improvement, a lower than expected complete cure
rate of 4.5 percent (normal looking nails and negative fungal
culture) was reached, which was surprising because a high
mycological cure is typically followed by clinical cure and the
combined endpoint complete cure.
The company has since engaged leading key opinion leaders to
help Moberg Pharma verify the results and better understand the
reasons for the conflicting outcome. The key question for the KOLs
has been to help the company understand why the high mycological
cure did not result in high complete cure. The KOLs found the
mycological cure rate of MOB-015 remarkable and very exciting, as
the first topical treatment with mycological cure rate at the same
level as oral terbinafine, the current gold standard for treatment
of onychomycosis. Furthermore, the onset of the antifungal effect
is more rapid than for oral terbinafine, with MOB-015 delivering 55
percent mycological cure at 6 months (vs 40 percent for oral
terbinafine) and 37 percent already at 3 months (vs 15
percent for oral terbinafine). In addition, after detailed
analysis of the data and individual photos from the study, the KOLs
concluded that while the vehicle technology enables high delivery
of terbinafine through the nail plate, its hydrating properties
also cause whitening/discoloration in nails. This phenomenon is
transient but makes the assessment of clinical cure challenging and
contributed to the low complete cure rate observed.
A solution to the problem was identified in collaboration with
the KOLs. Analysis of the available clinical data, including data
from the recent Phase 3 study, earlier Moberg Pharma studies as
well as from the literature, the KOLs as well as the company
experts conclude that the complete cure rate for MOB-015 likely can
be increased substantially by a shorter treatment period followed
by a maintenance period.
The current gold standard in onychomycosis is three months
treatment with oral terbinafine. Before this phase 3 trial for
MOB-015, it appeared unrealistic that a topical treatment would
achieve 70 percent mycological cure rate - the same level as oral
terbinafine. Treatment with MOB-015 resulted in 1000x higher
amounts of terbinafine in the nail plate and 40x higher in the nail
bed compared to oral terbinafine treatment. Considering also the
rapid onset and high mycological cure rate, the data indicates that
a shorter dosing regimen has the potential to increase complete
cure rates. The KOL evaluation concludes that once-daily treatment
period for not more than three months, followed by maintenance
dosing once weekly until week 48 should maintain high
concentrations of terbinafine in the tissue, while reducing the
hydrating effects after the initial treatment phase and thus the
impact on the clinical cure assessment at week 52.
"The high mycological cure rate demonstrated is very
impressive and given the rapid onset of the antifungal effect,
MOB-015 offers exciting benefits. I will definitely use it for my
patients. A higher complete cure rate is likely to be achieved with
a shorter treatment period and this would also be much more
attractive to patients", said Dr Boni
Elewski, Professor and Chair of the Department of
Dermatology, University of Alabama.
"I am a strong supporter of this concept. With an optimized
dosing regimen this product has great potential and may become the
preferred therapeutic option, not only for monotherapy, but also as
maintenance therapy to reduce recurrence after oral treatment",
said Dr Aditya Gupta, Professor, Department of Medicine,
University of Toronto.
"Based on decades of experience with terbinafine and the
excipients used in MOB-015, I believe a shorter treatment period
has the potential to provide higher complete cure rates. Killing
the fungus is the driver of also reaching complete cure", said
Dr Jan Faergemann, Professor in
Dermatology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Since the primary endpoint as well as secondary endpoints were
met in the North American trial and provided that the second study
also produces positive results, these studies could form a basis to
register the product. The timing to optimize the dosing regimen
will depend on the outcome of the EU trial.
"From a medical and commercial perspective, a regimen with
daily dosing for up to three months followed by less frequent
treatment, is highly attractive and further improves the target
product profile of MOB-015. This is further supported by U.S.
market data indicating that real-life usage of current topicals on
average is 3-4 months, despite being labeled for 48 weeks' daily
treatment", said Dr. Amir
Tavakkol, CSO of Moberg Pharma AB.
"We are very grateful for the thorough analysis of the key
opinion leaders which not only shed light on the conflicting
data points, but also strengthened our conviction that
MOB-015 has the potential to become the future market leader in
onychomycosis", said Anna Ljung,
CEO of Moberg Pharma AB.
Press conference
An investor Q&A will be held in a telephone conference today,
January 22, 2020, at 3:00 p.m. CET. Dial-in: SE: +46-8-505-583-53, US:
+1-833-526-83-80
Definitions of endpoints and topline results in the North
American Phase 3 study for MOB-015
Complete cure - Primary endpoint
The primary endpoint in the study is complete cure at week 52,
which is a composite measure of mycological cure and clinical
cure. The primary endpoint was met, since significantly more
patients in the MOB-015 group - 4.5 percent - reached complete cure
compared to none in the control group (p=0.019).
Mycological cure
Mycological cure is an objective measure composed of two laboratory
results: fungal culture and KOH microscopy. The physician/nurse
takes nail clippings, which are sent to a central laboratory for
analysis. If fungus cannot be cultured from the sample and fungal
elements subsequently cannot be seen in a microscopic examination,
the nail is mycologically cured (fungus free). A 70 percent
mycological cure after one year is remarkably high for a topical
treatment and on par with the best oral treatment. Mycological cure
is defined in the study as a key secondary endpoint.
Clinical cure
Clinical cure is a subjective measure where an experienced
physician at each clinic performs a visual assessment of how much
of the nail is affected by onychomycosis. No signs of infection
should be visible on the nail to achieve complete cure. This
endpoint is difficult to determine and takes different time to
achieve for different nails, depending among other things on the
condition of the nail at treatment start. The clinical cure was
identical to the complete cure.
Treatment success
Since the difficulty in achieving complete cure in 52 weeks is well
known, Treatment success is also reported, a composite measure of
mycological cure combined with a clinical assessment that the nail
should be clear or almost clear (up to 10 percent affected nail
area). Treatment success was reached in 15.4 percent of the
patients and was significantly better than the control group
(p=0.0018). Treatment success is defined in the study as a key
secondary endpoint.
The patient's own assessment
The patient's own assessment is a subjective measure where the
patient assesses the improvement in the nail according to a
standardized scale. Of the patients who completed the study, 33
percent reported that their treated toenails were completely cured
or almost cured. In addition, 83 percent of the patients reported a
visible improvement after just twelve weeks of treatment.
About the Phase 3 study in North
America
The recently completed Phase 3 study was conducted at 32 sites in
the U.S. and Canada and included a
total of 365 patients, 246 of whom received MOB-015 and 119 who
were in the control group and received the vehicle. The patients
had at least one great toenail that was 20-60 percent affected.
Treatment was administered once daily for 48 weeks and patients
were followed up for a total of 52 weeks. A second Phase 3 study is
currently underway in Europe
comprising 452 patients and is expected to be finalized in spring
2020. The setup in the European study in similar to the North
American study, the only difference is that instead of being
vehicle-controlled, in EU, MOB-015 is compared head to head against
the most widely used topical treatment.
About this information
This is information that Moberg Pharma AB (publ) is obliged to make
public pursuant to the EU Market Abuse Regulation (MAR). The
information was submitted for publication, through the contact
persons set out above at 08.00 a.m.
CET on January 22nd, 2020.
CONTACT:
For additional information, please contact:
Anna Ljung
CEO
Phone: +46-707-66-6030
E-mail: anna.ljung@mobergpharma.se
Peter Wolpert
Executive Chairman
Phone: +1-908-432-2203, +46-707-35-7135
E-mail: peter.wolpert@mobergpharma.se
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The following files are available for download:
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Expert evaluation
clarifies Phase 3 results and provides strong support for
MOB-015
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SOURCE Moberg Pharma