STAINES-UPON-THAMES, United
Kingdom, Sept. 23, 2019
/PRNewswire/ -- Mallinckrodt
plc (NYSE: MNK), a global biopharmaceutical company, today
announced positive top-line results from its pivotal Phase 3
clinical trial of its investigational StrataGraft®
regenerative tissue. The study, which met both primary endpoints,
evaluated the efficacy and safety of a single application of
StrataGraft in the treatment of deep partial-thickness thermal
burns. Each study participant served as his or her own control.
Results showed that a significantly smaller area of burn wounds
treated with StrataGraft tissue required autografting by three
months compared to the area of burn wounds treated exclusively with
autograft (p<0.0001). Additionally, results showed that the
proportion of StrataGraft-treated wounds that achieved durable
wound closure at three months exceeded the pre-defined threshold
for statistical significance.
Based on the positive Phase 3 data, Mallinckrodt plans to submit a Biologics License
Application for StrataGraft tissue to the FDA in the first half of
2020. StrataGraft tissue is an investigational product, and its
safety and effectiveness have not yet been established by the U.S.
Food and Drug Administration (FDA).
"Treatment advances are needed that can help minimize or
eliminate the need to harvest skin tissue for autografting, as the
second wound created by removing healthy skin can be associated
with complications and can be even more painful than the burn wound
itself," said Dr. James H. Holmes IV, study co-lead
investigator and Director of Wake Forest Baptist Medical
Center's Burn Center. "The positive top-line results of
the Phase 3 trial suggest that this investigational regenerative
tissue, if approved, could provide burn surgeons with an
alternative treatment option for deep partial-thickness burns."
Autograft is considered to be a standard of care by many for
deep partial-thickness thermal burns. Such burns are complex skin
injuries in which the damage extends through the entire epidermis
(outermost layer of skin) and into the lower part of the dermis
(innermost layer of skin). As autograft involves the surgical
harvesting of healthy skin from an uninjured site on the patient
and transplanting the skin graft to the injury, patients are left
with two wounds requiring care. Patients who receive an autograft
may experience pain, itching, scarring and impaired function at the
donor site.
"Achieving the co-primary endpoints in our pivotal Phase 3 trial
and exceeding statistical thresholds for both endpoints represents
an important development milestone for StrataGraft tissue, which
has the potential to help patients suffering from deep
partial-thickness thermal burns. Coupled with the recently
announced positive Phase 3 results for terlipressin in hepatorenal
syndrome, or HRS, type 1, these Phase 3 results demonstrate our
ability to design and execute successful development programs
targeting complicated, serious conditions," said Steven Romano, M.D., Executive Vice President
and Chief Scientific Officer at Mallinckrodt. "We are committed to providing
StrataGraft to patients in need as a potential paradigm-changing
treatment and alternative to autograft, if approved. We would like
to thank the study participants and investigators in the Phase 3
clinical trial and all of the others who have helped us advance the
clinical development program for this investigational
product."
Design and Results of Phase 3 Study (STRATA2016)
The
pivotal open-label, controlled, randomized, multicenter Phase 3
trial in adults evaluated the efficacy and safety of a single
application of StrataGraft tissue in the treatment of deep
partial-thickness thermal burns. The study enrolled 71 study
participants across 12 clinical sites in the United States. Study participants were age
18 years and older and had 3-49% total body surface area complex
skin defects caused by thermal burns that contained intact dermal
elements for which surgical excision and autografts were clinically
indicated. The study design used an intra-patient control, in which
two similar areas of burn injury on the same study participant were
randomly assigned to either standard of care (autograft) or
StrataGraft treatment.
The co-primary endpoints included autograft sparing (the
difference in the percent area of thermal burn wounds treated with
StrataGraft tissue that required autografting compared with the
control autograft treatment sites by three months), and durable
wound closure (the proportion of study participants achieving
durable wound closure of the StrataGraft-treated site at three
months without autograft placement).
Key co-primary endpoints findings included the following:
- On average, 4% of the area of StrataGraft-treated sites
required autografting by three months. By design, 100% of the area
of control-treated sites was autografted and an additional 2% of
the area required subsequent autografting by three months. This
resulted in a 98% reduction in the area requiring autograft in the
StrataGraft-treated sites compared to the control-treated sites
(p<0.0001).
- 83% of burn wounds treated with StrataGraft tissue alone
achieved durable wound closure at the treatment site at three
months post-placement (95% confidence interval: 74.4-91.8%, meeting
the pre-defined threshold of statistical significance). As a
reference, 86% of the burn wounds treated with a single application
of autograft achieved durable wound closure at three months
post-placement (95% confidence interval: 77.8-94.0%).
The safety profile of StrataGraft tissue was comparable to that
of autograft. Pruritus was the most commonly reported
treatment-emergent adverse event (TEAE), occurring in 25 of 71
(35%) study participants treated with StrataGraft tissue (of which
11 of the 25 were possibly related to study treatment). All study
treatment-related TEAEs were mild or moderate in severity. No local
infections were related to StrataGraft treatment.
For more information about the design of the Phase 3 clinical
trial, visit www.clinicaltrials.gov. (NCT03005106).
About StrataGraft Regenerative Tissue
StrataGraft
regenerative tissue is an investigational treatment being developed
to reduce or eliminate autograft in patients with severe thermal
burns. An engineered, bilayer tissue, StrataGraft is designed to
mimic natural human skin with both inner dermis-like and outer
epidermis-like layers. StrataGraft can be sutured, stapled or
secured with an adhesive. StrataGraft tissue is cryopreserved in
order to deliver viable cells upon application.
Mallinckrodt is currently evaluating
StrataGraft tissue in an ongoing Phase 2 trial for the treatment of
adults with full-thickness burns (also referred to as third-degree
burns). Mallinckrodt also plans to
study StrataGraft tissue in pediatric populations, and to initiate
a continued access clinical trial under an Expanded Access Program
(EAP) in the fall of 2019. The trial sites involved in the pivotal
Phase 3 trial (STRATA2016) will have the opportunity to participate
in that trial.
StrataGraft tissue is an investigational product, and its safety
and effectiveness have not yet been established by the FDA.
The FDA has granted StrataGraft tissue orphan drug status, and
it was among the first products designated by the Agency as a
Regenerative Medicine Advanced Therapy (RMAT) under the provisions
of the 21st Century Cures Act.
Funding and technical support for the continued development of
StrataGraft regenerative tissue, including the pivotal Phase 3
clinical study (STRATA2016) and the marketing approval registration
process for StrataGraft tissue in the
United States, is being provided by the Biomedical Advanced
Research and Development Authority (BARDA), under the Assistant
Secretary for Preparedness and Response, within the U.S. Department
of Health and Human Services, under Project BioShield Contract No.
HHSO100201500027C. The BARDA contract supports additional projects,
including clinical trials for use in pediatric populations. These
efforts are part of BARDA's strategy to build emergency
preparedness in response to mass casualty events involving trauma
and thermal burns by developing novel medical countermeasures for
adult and pediatric populations. In the case of a mass casualty
thermal burn event, the Government Accountability Office estimates
that more than 10,000 patients might require thermal burn
care.1 The limited number of specialized burn
centers and related medical infrastructure in the United States creates a public health need
for therapies that could be deployed quickly for use in these and
other care sites.
About Deep Partial-thickness Thermal Burns
Deep
partial-thickness thermal burns are complex skin injuries in which
the damage extends through the entire epidermis (outermost layer of
skin) and into the lower part of the dermis (innermost layer of
skin).
Autograft is considered to be a standard of care by many for
deep partial-thickness thermal burns. It involves the surgical
harvesting of healthy skin tissue from an uninjured site on the
patient and transplanting the skin graft to the injury. While this
process can be effective in providing closure of the original
wound, it has significant limitations related to the donor site
wounds created during surgical removal of the skin tissue for
grafting. Donor site wounds are extremely painful and can create
risks of additional scarring and infection. In addition, the amount
of healthy skin available for harvesting is frequently limited in
those patients with large burns, necessitating sequential
re-harvesting of available donor sites. As a result, there is an
urgent need for alternatives to donor site harvesting for the
treatment of severe burns.
ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of
multiple wholly owned subsidiaries that develop, manufacture,
market and distribute specialty pharmaceutical products and
therapies. The company's Specialty Brands reportable segment's
areas of focus include autoimmune and rare diseases in specialty
areas like neurology, rheumatology, nephrology, pulmonology and
ophthalmology; immunotherapy and neonatal respiratory critical care
therapies; analgesics and gastrointestinal products. Its Specialty
Generics reportable segment includes specialty generic drugs and
active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
Mallinckrodt uses its website as a
channel of distribution of important company information, such as
press releases, investor presentations and other financial
information. It also uses its website to expedite public access to
time-critical information regarding the company in advance of or in
lieu of distributing a press release or a filing with the U.S.
Securities and Exchange Commission (SEC) disclosing the same
information. Therefore, investors should look to the Investor
Relations page of the website for important and time-critical
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information is made available on the Investor Relations page of the
website.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
STATEMENTS
This release includes forward-looking statements
with regard to StrataGraft regenerative tissue, including
expectations with regard to clinical data and regulatory filings,
future research, its potential impact on patients, and anticipated
benefits associated with its use. The statements are based on
assumptions about many important factors, including the following,
which could cause actual results to differ materially from those in
the forward-looking statements: clinical trial results;
satisfaction of regulatory and other requirements; actions of
regulatory bodies and other governmental authorities; changes in
laws and regulations; issues with product quality, manufacturing or
supply, or patient safety issues; and other risks identified and
described in more detail in the "Risk Factors" section of
Mallinckrodt's most recent Annual
Report on Form 10-K and other filings with the SEC, all of which
are available on its website. The forward-looking statements made
herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to
update or revise any forward-looking statement, whether as a result
of new information, future events and developments or otherwise,
except as required by law.
CONTACTS
Media Relations
Carin
Ganz (trade and general media)
W2O for Mallinckrodt
212-301-7217
cganz@w2ogroup.com
Daniel Yunger (financial
media)
Kekst CNC for Mallinckrodt
212-521-4879
mallinckrodt@kekstcnc.com
Investor Relations
Daniel J.
Speciale, CPA
Vice President, Investor Relations and IRO
314-654-3638
daniel.speciale@mnk.com
Mallinckrodt, the "M" brand mark and
the Mallinckrodt logo are trademarks of
a Mallinckrodt company. Other brands
are trademarks of a Mallinckrodt
company or their respective owners. ©2019 Mallinckrodt. US-1901670 09/19
1 https://www.gao.gov/assets/590/588738.pdf.
Accessed April 23, 2019.
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SOURCE Mallinckrodt plc