TARRYTOWN, N.Y., Jan. 9, 2020 /PRNewswire/ --
Approximately 25% decrease in total bone lesions (both new
and existing) driven by nearly 90% reduction in formation of new
lesions in patients with fibrodysplasia ossificans progressiva
(FOP)
Regeneron plans to discuss regulatory submission with
regulatory authorities; pediatric trial planning underway
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)
today announced results from LUMINA-1, a 44-patient,
Phase 2, double-blind placebo-controlled trial evaluating
garetosmab (REGN2477) in patients with fibrodysplasia ossificans
progressiva (FOP). FOP is an ultra-rare genetic disorder with
no approved treatments that leads to abnormal bone formation
resulting in skeletal deformities, progressive loss of mobility and
premature death. On the primary analysis after 28 weeks of
treatment, garetosmab decreased total lesion activity (both new and
existing lesions) compared to placebo by 25% as measured by PET
bone scans (p=0.07); this result was driven by a nearly 90%
decrease compared to placebo in the number of new lesions, as
measured by PET. Correspondingly, there was an approximate 25%
relative decrease in bone lesion volume (both new and existing
lesions) as measured by CT scan (p=0.37), also driven by a nearly
90% decrease in the number of new bone lesions as measured by CT.
Patient-reported flare-ups were reduced by 50% (nominal p=0.03).
Investigator-reported adverse events of flare-ups were 10% for
garetosmab and 42% for placebo.
In people with FOP, abnormal bone formation occurs in soft
tissue outside of the normal skeleton, a process known as
heterotopic (in the wrong place) ossification (HO). Regeneron
scientists discovered the role of Activin A in FOP, a critical
protein in the development of HO, and used our
VelocImmune® technology to invent garetosmab, a
monoclonal antibody that reduces the formation of heterotopic bone
lesions by neutralizing the Activin A protein.
"These results are the culmination of
Regeneron's long-term commitment to FOP scientific
research, starting with our collaborations in the 1990s with
Drs. Richard Harland at the University of
California at Berkley and Frederick Kaplan at the
University of Pennsylvania. We are
grateful to all the physicians and patients and their families who
have participated in this program and advised us throughout the
process," said George D.
Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at
Regeneron. "This disease is relentless and devastating, leaving
many patients wheelchair-bound or locked in a position unable to
move, with a dramatically curtailed lifespan. We believe garetosmab
may offer important new hope that can potentially transform the
course of FOP and look forward to working closely with the FDA and
other regulatory authorities to make garetosmab available."
"The prevention of new heterotopic bone is of paramount
importance to the treatment of FOP," said Frederick S. Kaplan, M.D., The Issac & Rose
Nassau Professor of Orthopaedic Molecular Medicine at The Perelman
School of Medicine of the University of
Pennsylvania and the global primary investigator for
LUMINA-1. "The preliminary results of the LUMINA-1 clinical trial
are encouraging as these results clearly show a great reduction in
the formation of new lesions, which is incredibly important when we
consider future studies in pediatric populations."
"Now we have promising first results from a placebo-controlled
trial showing a decrease of new heterotopic bone formation and
flare-ups with a nearly 90% reduction in the incidence of new HO, a
groundbreaking result for people with FOP," said Marelise Eekhoff, M.D., Ph.D., Head of the
International Amsterdam FOP Expert Center at Amsterdam University
Medical Centers (Amsterdam UMC) and a LUMINA-1 investigator. "This
trial also significantly improves our understanding of the disease
by demonstrating that untreated people with FOP experience far more
frequent and widespread new bone lesions than previously thought,
and that these new lesions appear dependent on Activin A for their
formation."
LUMINA-1 enrolled 44 adult patients (18-60 years old) from
North America (U.S. and
Canada) and Europe with a clinical diagnosis of FOP and
documentation of an ACVR1 genetic mutation. Patients in the trial
had a range of disease severity from localized functional
compromise to near-total immobility. The trial employed
18F-NaF PET imaging and CT scans to investigate the
effect of garetosmab on change in HO in patients with FOP.
18F-NaF is a widely approved and extensively used
bone-seeking PET tracer with high sensitivity to detect abnormal
bone growth, turnover and mineralization in several bone-related
diseases such as Paget's disease and cancers with bone involvement.
LUMINA-1 has a three-period trial design consisting of a
randomized, double-blind placebo-controlled treatment period (6
months), open-label treatment period, during which placebo-treated
patients cross over to garetosmab treatment (6 months), and
open-label follow-up treatment. The primary analysis was recorded
at week 28.
"These data prove the hypothesis that Activin A is required for
the formation of new heterotopic bone lesions in people with FOP.
Activin A inhibition by garetosmab markedly reduced the occurrence
of new abnormal bone formation and flare-ups, providing a true
opportunity for a disease-modifying therapy for FOP," said
Aris Economides, Ph.D., Vice
President of Research at Regeneron. "We hope garetosmab can change
the course of disease for these long-suffering patients around the
world."
"With the release of the LUMINA-1 trial results, we are
encouraged that this investigational drug may help prevent the
progression of FOP," said L. Adam
Sherman, Director, Research Development and Partnerships at
the International Fibrodysplasia Ossificans Progressiva Association
(IFOPA). "FOP is a progressive, devastating disease with no
approved treatment options. The release of these data is a
significant step forward towards a meaningful treatment option and
a brighter future ahead for the FOP
Community."
During the 28-week treatment period treatment emergent adverse
events (TEAEs) occurred in 100% of both treated and placebo groups;
the majority were mild to moderate in severity. Notable imbalances
in TEAEs included epistaxis (50.0% vs 16.7%) and skin events
(madarosis [loss of eyebrows, 25.0% vs 0%], acne [30.0% vs 8.3%]
and a composite of skin infections including abscess, carbuncle,
folliculitis, furuncle). Two treated patients in the open-label
portion of the trial developed serious abscesses requiring
hospitalization for drainage but resolved while continuing
garetosmab treatment. Nineteen out of 20 garetosmab patients and 24
out of 24 placebo-group patients completed the 28-week treatment
period. One patient in the open-label portion of the trial died due
to trauma unrelated to treatment.
Detailed results from this trial will be used as the basis of
regulatory submissions. The data will also be submitted for
presentation at a future medical congress. Plans for a pediatric
trial are also underway.
About Fibrodysplasia Ossificans
Progressiva (FOP)
Fibrodysplasia
ossificans progressiva (FOP) is a relentless, progressive,
ultra-rare genetic disorder in which muscles, tendons and ligaments
are progressively replaced by bone, a process known as heterotopic
ossification (HO). There are approximately 800 patients diagnosed
with FOP worldwide, with many others thought to remain undiagnosed
or misdiagnosed.
HO of the jaw, spine, hip and rib cage can make it difficult to
speak, eat, walk or breathe, leading to weight loss and escalating
loss of mobility and skeletal deformity. People with FOP also
experience episodic, localized inflammation known as "flare-ups,"
although HO may occur both silently as well as in association with
symptoms. Most people with FOP are wheelchair bound by 30 years old
and the median age of survival is approximately 56 years. Death
often results from complications, such as pneumonia, heart failure
and aspiration stemming from HO and loss of mobility in the chest,
neck and jaw.
About Garetosmab (REGN2477)
Regeneron has been
engaged in FOP research for over two decades and helped to provide
fundamental insights in the biology and natural history of the
disease. Regeneron scientists discovered that Activin A plays a key
role in FOP by driving HO, the main pathology of FOP. Garetosmab is
a VelocImmune-derived fully-human monoclonal antibody that
binds and neutralizes Activin A, which is involved in the
development of heterotopic bone in people with FOP. Garetosmab is
currently being studied in adults with FOP.
In 2017, the U.S. Food and Drug Administration (FDA) granted
Fast Track designation for garetosmab for the prevention of HO in
patients with FOP. In the U.S. and European Union (EU), garetosmab
has been granted Orphan Designation. Garetosmab is currently under
clinical development, and its safety and efficacy have not been
evaluated by any regulatory authority.
About Regeneron
Regeneron (NASDAQ:
REGN) is a leading biotechnology company that invents
life-transforming medicines for people with serious diseases.
Founded and led for over 30 years by physician-scientists, our
unique ability to repeatedly and consistently translate science
into medicine has led to seven FDA-approved treatments and numerous
product candidates in development, all of which were homegrown in
our laboratories. Our medicines and pipeline are designed to help
patients with eye diseases, allergic and inflammatory diseases,
cancer, cardiovascular and metabolic diseases, infectious diseases,
pain and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our
proprietary VelociSuite® technologies,
such as VelocImmune®, which uses a unique
genetically-humanized mouse to produce optimized fully-human
antibodies and bispecific antibodies, and through ambitious
research initiatives such as the Regeneron Genetics Center, which
is conducting one of the largest genetics sequencing efforts in the
world.
For additional information about the company, please
visit www.regeneron.com or follow @Regeneron on
Twitter.
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