Mereo BioPharma Group plc (NASDAQ: MREO, AIM: MPH), "Mereo" or the
"Company," today announced additional endpoint data from the
Company’s Phase 2b dose-ranging "ASTEROID" clinical study of
setrusumab (BPS-804), an anti-sclerostin antibody, in adults
with Type I, III or IV osteogenesis imperfecta (“OI”). These
additional prespecified endpoint data build upon the Company’s
12-month topline data from the ASTEROID study announced in November
2019, which demonstrated a dose-dependent, statistically
significant bone building effect of setrusumab at multiple
anatomical sites in adult OI patients (irrespective of OI subtype).
OI is a rare disorder characterized by fragile bones and reduced
bone mass with no approved treatments.
“Based upon our review of the comprehensive data
set from the Phase 2b ASTEROID study, these additional prespecified
analyses support our previous conclusions that setrusumab is
building bone at the lumbar spine and is increasing bone strength
at multiple peripheral sites in adult OI patients,” said Dr.
Alastair MacKinnon, Chief Medical Officer of Mereo. “We believe
these additional endpoint data, together with the totality of the
12-month topline data and trend in fracture rate reduction in the
high dose cohort, are fully supportive of moving forward with our
planned pivotal trial in children with OI. To this end, we have
made additional progress on the regulatory front, including a
positive recent meeting with the European Medicines Agency (“EMA”),
and are currently preparing for a Type B End-of-Phase 2 meeting
with the FDA, scheduled for the first quarter of 2020.”
“Finite element analysis (“FEA”) is one of the best measures
available to monitor bone strength in clinical studies, being
sensitive to important changes in trabecular and cortical bone as
well as overall bone structure. In OI patients given setrusumab for
12 months, the FEA technique was used to assess forearm (radius)
bone strength at the beginning and end of the treatment period,”
said Dr. Ken Poole, Reader in Metabolic Bone Disease at the
University of Cambridge. “These new data are consistent with
an effect of setrusumab at the high dose on improving radius bone
strength as evidenced by a better ability to resist experimental
deformation and improved failure load. There are no currently
approved therapies for osteogenesis imperfecta, and treatment
options are greatly needed."
Additional Prespecified Efficacy
Endpoint Results
Finite Element Analysis to Measure Bone Strength
by Failure Load and Stiffness at the Radius (Second Primary
Endpoint on a Hierarchical Basis)
The primary endpoint of the ASTEROID study was
change in Trabecular Volumetric Bone Mineral Density (Tr. vBMD) of
the radius (wrist) over baseline after 12 months of treatment as
measured by High Resolution peripheral Quantitative Computed
Tomography (HR-pQCT), followed by bone strength as calculated using
FEA, a derived measurement of the mechanical strength gained by
accumulated material in the bone.
Setrusumab demonstrated a dose dependent
increase in both failure load and stiffness at the radius at 12
months, achieving statistical significance in the high dose cohort
across both of these parameters (p=0.037 for failure load and
p=0.022 for stiffness). FEA is based on the totality of the bone
compartments (trabecular and cortical bone) and these data
demonstrate that treatment with high dose setrusumab results in a
significant increase in bone strength at the peripheral bone sites,
consistent with the previously reported statistically significant
increases in total vBMD as measured by HRpQCT (a secondary endpoint
of the study).
Table 1: Increase in Failure Load at the radius
determined by FEA and by dose cohort (all OI subtypes)
Dose Cohort |
Mean % Change in Failure Load at 12 months |
P value at 12 months |
High (n=27) |
+2.0% |
p<0.037 |
Medium (n=20) |
+1.1% |
NS |
Low (n=22) |
-0.06% |
NS |
Table 2: Increase in stiffness at the radius
determined by FEA and by dose cohort (all OI subtypes)
Dose Cohort |
Mean % Change in Stiffness at 12 months |
P value at 12 months |
High (n=27) |
+2.2% |
P<0.022 |
Medium (n=20) |
+1.0% |
NS |
Low (n=20) |
+0.1% |
NS |
Trabecular Bone Score at the Lumbar Spine
(Prespecified Exploratory Secondary Endpoint)Trabecular bone score
(TBS) is a gray-level texture index determined from patient lumbar
spine dual-energy X-ray absorptiometry (DXA) scans that correlates
with 3D parameters of trabecular bone architecture thought to help
predict fracture. DXA is a well-established measurement tool of
bone mineral density (cortical + trabecular bone).
Setrusumab demonstrated a statistically
significant increase in TBS at both the high (p<0.001) and
medium dose cohorts (p<0.001). Importantly, the spine is
composed of both trabecular and cortical bone and these data
demonstrate efficacy of setrusumab in the trabecular bone
compartment at the lumbar spine which can be combined with the
previously reported data from HRpQCT at the radius showing the
impact of setrusumab on the cortical bone.
Table 3: Increase in TBS at the vertebral spine
(all OI subtypes)
Dose Cohort |
Mean % Change in Stiffness at 12 months |
P value at 12 months |
High (n=27) |
3.7% |
P<0.001 |
Medium (n=20) |
3.2% |
P<0.001 |
Low (n=22) |
-0.47% |
NS |
As previously reported, topline 12-month safety
results suggest setrusumab was safe and well tolerated in the
ASTEROID study.
Regulatory Progress Update As
part of the PRIME pathway, Mereo has discussed the results of the
Phase 2b ASTEROID study with the EMA. On the basis of the Phase 2b
data, the EMA supports the initiation of the planned pivotal
pediatric study in Europe on the basis of the previously approved
pediatric investigational plan (PIP). This is based on a primary
endpoint of fracture rate over a 12-month period in approximately
165 children aged 5 to <18 years old.
Mereo expects to conduct a Type B End-of-Phase 2
meeting with the U.S. Food and Drug Administration (FDA) in Q1 2020
to discuss the data from the Phase 2b ASTEROID study as well as the
proposed pediatric pivotal study design. Mereo intends to announce
the outcome of these discussions following the meeting.
About the Phase 2b ASTEROID
Study ASTEROID was a 12-month, randomized, double-blind,
Phase 2b dose-finding study in 112 adults diagnosed with type I,
III or IV Osteogenesis Imperfecta and a confirmed COL1A1/COL1A2
mutation who have fractured over the previous 5 years. ASTEROID was
the largest, prospectively-designed, interventional clinical study
to be performed in this patient group. The primary endpoint of the
study was the change over baseline in Tr vBMD of the wrist at 12
months, followed by bone strength measured by Finite Element
Analysts (hierarchical) assessed using HR-pQCT. Change from
baseline at 6 and 12 months for areal BMD at the lumbar spine, as
measured by DXA, was an important secondary endpoint. Additional
secondary endpoints included HR-pQCT parameters (such as total
vBMD), bone biomarkers, patient reported outcomes (PRO) and quality
of life measures. Fracture data were also collected throughout the
duration of the study, although the trial was not statistically
powered for fractures.
About Osteogenesis
ImperfectaOsteogenesis Imperfects (OI) is a rare genetic
disorder that is characterized by fragile bones and reduced bone
mass resulting in bones that break easily, loose joints and
weakened teeth. In severe cases patients may experience hundreds of
fractures in a lifetime. In addition, people with OI often suffer
muscle weakness, early hearing loss, fatigue, curved bones,
scoliosis, respiratory problems and short stature, leading to
significant impacts on overall health and quality of life. The
majority of cases of OI (estimated at approximately 90%) are caused
by a dominant mutation in a gene coding for type I collagen, a key
component of healthy bone. Current treatment of OI is supportive,
focusing on minimizing fractures and maximizing mobility, but to
date, there are no EMA or FDA approved treatments.
About SetrusumabSetrusumab is a
fully humanized monoclonal antibody that inhibits sclerostin, a
protein which inhibits the activity of bone-forming cells. The
mechanism of action of setrusumab could be particularly well suited
for the treatment of OI and has the potential to become the first
approved treatment option that could reduce fractures and improve
OI patients' quality of life. In addition to evaluating setrusumab
in adult OI patients, Mereo's Paediatric Investigation Plan (PIP)
has been approved by the European Medicines Agency (EMA) and a
study design has been agreed for a pivotal registration trial in
children, based on a primary endpoint of fracture rate over a
12-month period. The pivotal study will be conducted in
approximately 165 children aged 5 to <18 years old with OI,
initially in EU and Canada. Mereo continues to review the optimum
ratio of potential partnering and equity income to finance the
pivotal programme for setrusumab.
Mereo has obtained orphan drug designation in OI
for setrusumab in both the United States and the EU, in February
2017 setrusumab was accepted into the EMA’s adaptive pathways
program in the EU and, in November 2017 it was accepted into the
EMA’s Priority Medicines scheme (PRIME).
About Mereo BioPharmaMereo
BioPharma is a biopharmaceutical company focused on the development
and commercialization of innovative therapeutics that aim to
improve outcomes for patients with rare diseases. Mereo's strategy
is to selectively acquire product candidates for rare diseases that
have already received significant investment from pharmaceutical
and large biotechnology companies and that have substantial
preclinical, clinical and manufacturing data packages. Mereo’s lead
rare disease product candidate, setrusumab, has completed a Phase
2b dose ranging study in adult patients with osteogenesis
imperfecta (“OI”). Mereo’s second lead product candidate,
alvelestat, is being investigated in a Phase 2 proof-of-concept
clinical trial in patients with alpha-1 antitrypsin deficiency
(“AATD”) with topline data expected in mid-2020.
Mereo’s broader pipeline consists of four
additional clinical-stage product candidates; acumapimod for the
treatment of acute exacerbations of chronic obstructive pulmonary
disease (“AECOPD”), leflutrozole for the treatment of
hypogonadotropic hypogonadism (“HH”) in obese men, navicixizumab
for the treatment of platinum-resistant ovarian cancer (recently
licensed to Oncologie), and etigilimab for patients with advanced
or metastatic solid tumors.
Forward-Looking StatementsThis
document contains “forward-looking statements.” All statements
other than statements of historical fact contained in this
presentation are forward-looking statements within the meaning of
Section 27A of the United States Securities Act of 1933, as amended
(the “Securities Act”), and Section 21E of the United States
Securities Exchange Act of 1934, as amended (the “Exchange Act”).
Forward-looking statements usually relate to future events and
anticipated revenues, earnings, cash flows or other aspects of our
operations or operating results. Forward-looking statements are
often identified by the words “believe,” “expect,” “anticipate,”
“plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,”
“estimate,” “outlook” and similar expressions, including the
negative thereof. The absence of these words, however, does not
mean that the statements are not forward-looking. These
forward-looking statements are based on the Company’s current
expectations, beliefs and assumptions concerning future
developments and business conditions and their potential effect on
the Company. While management believes that these forward-looking
statements are reasonable as and when made, there can be no
assurance that future developments affecting the Company will be
those that it anticipates.
Factors that could cause actual results to
differ materially from those in the forward-looking statements
include risks relating to unanticipated costs, liabilities or
delays; failure or delays in research and development programs,
including expected timing of topline data for the Phase 2
proof-of-concept clinical trial evaluating the Company’s second
lead product candidate, alvelestat, in patients with alpha-1
antitrypsin deficiency; the safety and efficacy of the Company’s
product candidates and the likelihood of clinical data to be
positive and of such product candidates to be approved by the
applicable regulatory authorities; unanticipated changes relating
to competitive factors in the Company’s industry; risks relating to
the Company’s capitalization, resources and ownership structure,
including as a result of circumstances affecting the Company’s
former principal shareholder; the availability of sufficient
resources for company operations and to conduct or continue planned
clinical development programs, including the Company’s ability to
continue as a going concern; changes in law or regulations
affecting the Company.
All of the Company’s forward-looking statements
involve risks and uncertainties (some of which are significant or
beyond its control) and assumptions that could cause actual results
to differ materially from the Company’s historical experience and
its present expectations or projections. The foregoing factors and
the other risks and uncertainties that affect the Company’s
business, including those described in its Annual Report on Form
20-F, Reports on Form 6-K and other documents filed from time to
time by the Company with the United States Securities and Exchange
Commission (the “SEC”) and those described in other documents the
Company may publish from time to time should be carefully
considered. The Company wishes to caution you not to place undue
reliance on any forward-looking statements, which speak only as of
the date hereof. The Company undertakes no obligation to publicly
update or revise any of our forward-looking statements after the
date they are made, whether as a result of new information, future
events or otherwise, except to the extent required by law.
Mereo BioPharma Contacts:
Mereo |
+44 (0)333 023 7300 |
Denise Scots-Knight, Chief
Executive Officer |
|
Richard Jones, Chief Financial
Officer |
|
|
|
Cantor Fitzgerald Europe
(Nominated Adviser and Broker to
Mereo) |
+44 (0)20 7894
7000 |
Phil Davies |
|
Will Goode |
|
|
|
Burns McClellan (US
Public Relations Adviser to Mereo) |
|
Lisa Burns |
+01 (0) 212 213
0006 |
Steve Klass |
|
|
|
FTI Consulting (UK Public
Relations Adviser to
Mereo) |
|
Simon Conway |
|
Ciara Martin |
+44 (0)20 3727
1000 |
|
|
Investors:investors@mereobiopharma.com
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