ENGLEWOOD, Colo., Jan. 16, 2018 /PRNewswire/ -- Ampio
Pharmaceuticals, Inc. (NYSE MKT: AMPE) today reported a heavy
schedule of meetings throughout the four-day conference,
predominately with significant pharmaceutical companies discussing
the successful clinical results of the company's second pivotal
phase III trial announced Dec. 14,
2017. The discussions also explored whether
Ampion™ could provide not only relief of signs and
symptoms of osteoarthritis of the knee (OAK) but also be "a
disease-modifying drug" for this condition.
David Bar-Or, M.D., Ampio's CSO explained: "OAK, over time,
causes progressive loss of cartilage in the knee, which is one of
the reasons for limited joint function and chronic pain in this
condition (although cartilage has no nerve endings, sub chondral
bone does). There are three types of chondrocytes (cells making
cartilage) in OAK: 1. Normal chondrocytes, 2. dying chondrocytes
and 3. fibroblast like chondrocytes (FLC). The FLC make the wrong
type of collagen and is not beneficial to the knee. As the patient
ages the replacement of new cartilage begins to lag behind the rate
of loss of cartilage and this process is accelerated by OAK. Thus
the 'disease modification'
mechanism that these pharmaceutical companies are extremely
interested in, would either increase the rate of generation of new
normal cartilage or provide an anti-apoptotic (death protection)
effect that would extend the life of the existing normal
cartilage-producing chondrocytes. Scientists from these
pharmaceutical companies noted that the peer reviewed publications
and confidential information provided to them, suggest aspects of
the Mode of Action (MOA) of Ampion™ appear to support both
possibilities.
"We have already demonstrated and/or published in-vitro data
indicating that Ampion™:
- decreases vascular permeability (an upstream event in
inflammation),
- mobilizes and differentiates bone marrow-derived mesenchymal
stem cells into normal chondrocytes,
- protects cells from apoptosis (programmed cell death) and
autophagia,
- up-regulates both COX-2 mRNA and COX-2 protein in human
synovial fibroblasts, human normal and osteoarthritic chondrocytes,
and peripheral blood monocytes leading to increased production of
the anti-inflammatory prostaglandins PGD2 and its metabolite
15-d-PGJ2,
- inhibits the differentiation of M0 macrophage into the M1 pro
inflammatory macrophage phenotype,
- more unpublished data supporting the molecular changes that
decrease OAK inflammatory damage and helps restore healthy
chondrocytes and normal cartilage accretion.
"Because severe disease is associated with denudement of bone,
MRI was used to quantitatively analyze and compute
cartilage-covered and bare, denuded (no cartilage) bone areas for
each opposing surface of the knee joint. Areas with exposed
(denuded) bone were identified in the medial or lateral surface
compartments of the knee. Some patients have disease predominantly
in the medial compartment whereas others have more disease in the
lateral compartment or more symmetrically. The open label study of
7 patients, each receiving 3 injections two weeks apart, that
preceded the 40 patient STRUT study suggested that we should
compare medial compartment disease and lateral compartment disease
separately to appropriately matched placebo controls."
Dr. Bar-Or continued: "A review of the quantitative MRI analysis
of cartilage from the double-blind, three injections, vehicle
controlled STRUT study (N=40) at 52 weeks compared to baseline was
never published because the study was powered only to investigate
the safety of the three injections of Ampion™ or saline at
two week intervals. However, the MRI analysis after 52 weeks did
provide some tantalizing results.
"A total of 37 patients had MRI data at baseline and at week 52.
Of those, 20 patients had medial (n=10) or lateral disease (n=10)
and the remaining (n=17) had either no denudement or symmetrical
disease. Changes in cartilage thickness were examined across 6
anatomically defined sub regions, and patients with medial disease
and lateral disease were analyzed separately.
"Among patients with medial disease, patients treated
with Ampion™ had less cartilage thickness loss than patients
treated with saline in all 6 medial sub
regions. For instance, the mean cartilage thickness change over
covered area of subchondral bone was -3μm for patients receiving
Ampion™ and -34μm for patients receiving saline.
"Among patients with lateral disease, patients
treated with Ampion™ had less cartilage loss than patients treated
with saline in 5 of 6 lateral sub regions. Only
Ampion™ patients showed increased cartilage thickness, in 2 lateral
sub regions, as follows:
- Central part of the Lateral femorotibial compartment: +1μm for
Ampion™ treated patients vs. -106μm for saline treated
patients.
- Covered area of subchondral bone: +20μm for Ampion™ treated
patients compared to -17μm for the saline group.
"We are encouraged by the results of the MRI analysis from the
STRUT study. These results support those from the 'in vitro' work, and suggest Ampion™ does
have the potential to provide a structure modifying/preserving
therapy for osteoarthritis."
Detailed results of the STRUT study were published as a feature
article in the peer-reviewed journal Orthopedics in 2017:
https://www.healio.com/orthopedics/journals/ortho/2017-1-40-1/%7B2ac26c9c-539c-4d93-b3a9-428849cd904e%7D/preliminary-trial-of-intra-articular-lmwf-5a-for-osteoarthritis-of-the-knee
Michael Macaluso, Ampio's CEO
stated: "This MRI analysis supports the anecdotal reports of
prolonged pain and function relief, beyond 20 weeks we have
received from patients with moderate to severe OAK treated with
Ampion™. Ampio will perform larger studies to support a 'disease modification or healing label,'
post marketing, possibly with more injections over a longer time
period, in compliance with FDA recommendations should our BLA be
accepted and approved. Additional information on these subjects is
contained in the press releases below."
- February 25, 2015, "Ampio Pharma
(AMPE) Reports Top-Line Results from STRUT Study"
http://ampiopharma.com/uncategorized/ampio-announces-top-line-results-double-blind-multiple-intra-articular-injections-strut-study-ampion-patients-moderate-severe-osteoarthritis-knee/
- November 12, 2014, "Ampio
Pharmaceuticals, Inc. Updates Status of Clinical Trials and
Manufacturing Facility"
http://ampiopharma.com/news/ampio-updates-status-clinical-trials-manufacturing-facility-2/
Regulatory Exclusivity and IP protection:
The Company
believes that Ampion™, a low molecular weight fraction
of human serum albumin with anti-inflammatory properties, will be
identified as a "reference product" upon FDA approval of their
BLA. Reference products are granted twelve years of
exclusivity under the PHS Act, 42 U.S.C. § 262(k)(7). Specifically,
FDA is not permitted to approve an application for a biosimilar or
interchangeable product until 12 years after the date of the first
licensure of the reference product. The existing Ampion™ portfolio
has patent coverage in all major jurisdictions throughout the world
(U.S., Europe, Australia, Brazil, Canada, China, Eurasia, Hong
Kong, India, Indonesia, Israel, Japan, Korea, Mexico, Malaysia, New
Zealand, Philippines,
Singapore, South Africa) for pharmaceutical compositions
and methods of treating a range of conditions. The portfolio
includes 125 issued patents and 85 pending applications throughout
seven primary patent families having expiration dates that extend
to 2035.
About Osteoarthritis
Osteoarthritis (OA) is a
progressive disorder of the joints involving degradation of the
intra-articular cartilage, joint lining, ligaments, and bone. The
incidence of developing osteoarthritis of the knee over a lifetime
is approximately 45%. As this disease is associated with age,
obesity, and diabetes, this number will continue to grow. Certain
risk factors in conjunction with natural wear and tear lead to the
breakdown of cartilage. Osteoarthritis is caused by inflammation of
the soft tissue and bony structures of the joint, which worsens
over time and leads to progressive thinning of articular cartilage.
Other symptoms include narrowing of the joint space, synovial
membrane thickening, osteophyte formation and increased density of
subchondral bone.
About Ampio Pharmaceuticals
Ampio Pharmaceuticals,
Inc. is a development stage biopharmaceutical company primarily
focused on the development of therapies to treat prevalent
inflammatory conditions for which there are limited treatment
options. We are developing compounds that decrease inflammation by
(i) inhibiting specific pro-inflammatory compounds by affecting
specific pathways at the protein expression and at the
transcription level; (ii) activating specific phosphatase or
depletion of the available phosphate needed for the inflammation
process; and (iii) decreasing vascular permeability.
Forward-Looking Statements
Ampio's statements in this
press release that are not historical fact, and that relate to
future plans or events, are forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements can be identified by the use of words
such as "believe," "expect," "plan," "anticipate," and similar
expressions. These forward-looking statements include statements
regarding Ampio's expectations with respect to Ampion™, as well as
those associated with clinical trials, expected results, regulatory
approvals, the ability of Ampio to enter into partnering
arrangements, the Biological License Application (BLA) and
decisions and changes in business conditions and similar events,
all of which are inherently subject to various risks and
uncertainties. The risks and uncertainties involved include
those detailed from time to time in Ampio's filings with the
Securities and Exchange Commission, including without limitation,
under Ampio's Annual Report on Form 10-K and other documents filed
with the Securities and Exchange Commission. Ampio undertakes no
obligation to revise or update these forward-looking statements,
whether as a result of new information, future events or
otherwise.
Company Contact
Tom
Chilcott
Chief Financial Officer
Phone: (720) 437-6500
tchilcott@ampiopharma.com
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SOURCE Ampio Pharmaceuticals, Inc.