Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) and Mereo BioPharma
Group plc (NASDAQ: MREO) today announced interim data from the
Phase 2 portion of the Phase 2/3 Orbit study demonstrating that
treatment with setrusumab (UX143) significantly reduced incidence
of fractures in patients with OI with at least 6 months of
follow-up and continues to demonstrate ongoing and meaningful
improvements in lumbar spine bone mineral density (BMD). The data
were presented in a late-breaker presentation at the American
Society for Bone and Mineral Research 2023 Annual Meeting (ASBMR).
As of the cut-off date and following at least 6 months of
treatment with setrusumab, the annualized fracture rate across all
24 patients in the Phase 2 portion of the study was reduced by 67%.
In the 2 years prior to treatment with setrusumab all patients
experienced at least 1 fracture. The median annualized fracture
rate of 0.72 in the 2 years prior to treatment was reduced to 0.00
(n=24, p=0.042) during the mean treatment duration period of 9
months. Following initiation of treatment with setrusumab, 20
patients experienced no radiographic-confirmed fractures, and 4
patients experienced 7 radiographic-confirmed fractures in 5
separate events. These fractures exclude fractures of the fingers,
toes, skull, and face consistent with the Phase 3 study design.
“I have not yet encountered a patient with a fragility fracture
while on setrusumab, and this may result from setrusumab’s effects
on the skeleton, improving the rate of new bone formation and bone
quality,” said Gary Gottesman, M.D., Professor of Pediatrics and
Medicine, Washington University School of Medicine. “Some of the
kids feel well enough they are participating in activities that
they might normally avoid and have suffered some relatively minor
fractures.”
The reduction in annualized fracture rates was associated with a
clinically meaningful increase in BMD. At the 6-month timepoint,
treatment with setrusumab resulted in a mean increase in lumbar
spine BMD from baseline of 13% at 20 mg/kg (n=11) and 16% at 40
mg/kg (n=8), which represents the same substantial mean improvement
in Z-score of +0.85 for both dose groups at 6 months compared to a
combined mean baseline Z-score of –1.68. The small apparent
difference in BMD change from baseline is likely related to
differences in patients assigned to the two treated groups. There
was no statistically significant difference in BMD percent change
or Z-score change from baseline between the 20 and 40 mg/kg dosing
cohorts.
“These data provide compelling evidence that improved bone
mineral density, resulting from this unique mechanism of action,
reduced the risk of fractures and that treatment with setrusumab
could allow patients with OI to lead much more active lives with
fewer fractures,” said Eric Crombez, M.D., chief medical officer at
Ultragenyx. “I want to acknowledge the OI community and especially
thank the people living with OI and their caregivers who have aided
the setrusumab development program so that we may potentially offer
the first approved treatment option for this severe and disabling
disease.”
As of the data cut-off, there were no treatment-related serious
adverse events observed in the study. Reported adverse events were
generally consistent with those observed in the ASTEROID study with
infusion-related events and headache determined to be the most
common adverse events related to the study drug. There have been no
reported hypersensitivity reactions related to setrusumab. There
were no notable safety-related differences observed between dosing
groups or age groups.
The Phase 3 portion of the study is currently enrolling
approximately 195 patients at 50 sites across 12 countries.
U.S. residents can learn more by
visiting ultraclinicaltrials.com.
Analyst Day and Webcast Information
Ultragenyx will host an Analyst Day at 8:30 a.m. ET on Monday,
October 16, 2023 to discuss these data and to provide an update on
the company’s development pipeline. A live video webcast of the
program will be available at
https://www.webcaster4.com/Webcast/Page/359/49192. An archived
version of the remarks will also be available through the
Ultragenyx website.
The Setrusumab Phase 3 Program
The global, seamless Phase 2/3 Orbit study is evaluating the
effect of setrusumab on clinical fracture rate in patients aged 5
to <26 years. In the Phase 2 portion, 24 patients were
randomized 1:1 to receive setrusumab at one of two doses to
determine the optimal dosing strategy for Phase 3. The pivotal
Phase 3 portion of the study will include approximately 195
patients at 50 sites across 12 countries, randomized 2:1 to receive
setrusumab or placebo, with a primary efficacy endpoint of
annualized clinical fracture rate, excluding fingers, toes, skull,
and face. All patients will transition to an extension period and
receive open-label setrusumab after the Phase 3 primary analysis is
complete.
The global Phase 3 Cosmic study is an open-label, randomized,
active-controlled study in patients aged 2 to <7 years
evaluating setrusumab compared to intravenous bisphosphonates
(IV-BP) therapy on reduction in total fracture rate, including
morphometric vertebral fractures. The Cosmic study will enroll
approximately 65 patients at more than 20 sites across 8
countries.
About Osteogenesis Imperfecta (OI)
Osteogenesis Imperfecta (OI) includes a group of genetic
disorders impacting bone metabolism. Approximately 85% to 90% of OI
cases are caused by mutations in the COL1A1 or
COL1A2 genes, leading to either reduced or abnormal collagen
and changes in bone metabolism. The collagen mutations in OI can
result in increased bone brittleness, which contributes to a high
rate of fractures. Patients with OI also exhibit inadequate
production of new bone, which leads to decreased bone mass, bone
fragility and weakness. OI can also lead to bone deformities,
abnormal spine curvature, pain, decreased mobility, and short
stature. No treatments are approved for OI, which affects
approximately 60,000 people in the developed world.
About Setrusumab (UX143)
Setrusumab is a fully human monoclonal antibody that inhibits
sclerostin, a negative regulator of bone formation. Blocking
sclerostin is expected to increase new bone formation, bone mineral
density and bone strength in OI. In mouse models of OI, the use of
anti-sclerostin antibodies was shown to increase bone formation,
improve bone mass to normal levels, and increase bone strength
against fracture force testing to normal levels.
In 2019 Mereo BioPharma completed the Phase 2b dose-finding
study (ASTEROID) for setrusumab in 112 adults with OI.
The ASTEROID study demonstrated treatment with setrusumab
resulted in a clear, dose-dependent and statistically significant
effect on bone formation and bone density at multiple anatomical
sites among adult participants with OI.
Ultragenyx and Mereo BioPharma are collaborating on the
development of setrusumab globally based on the collaboration and
license agreement between the parties. The companies have developed
a comprehensive late-stage program to continue development of
setrusumab in pediatric and young adult patients across OI
sub-types I, III and IV.
About Ultragenyx
Ultragenyx is a biopharmaceutical company committed to bringing
novel products to patients for the treatment of serious rare and
ultra-rare genetic diseases. The company has built a diverse
portfolio of approved therapies and product candidates aimed at
addressing diseases with high unmet medical need and clear biology
for treatment, for which there are typically no approved therapies
treating the underlying disease.
The company is led by a management team experienced in the
development and commercialization of rare disease therapeutics.
Ultragenyx’s strategy is predicated upon time- and cost-efficient
drug development, with the goal of delivering safe and effective
therapies to patients with the utmost urgency. For more information
on Ultragenyx, please visit ultragenyx.com.
About Mereo BioPharma
Mereo BioPharma is a biopharmaceutical company focused on the
development of innovative therapeutics for rare diseases. The
Company has two rare disease product candidates, setrusumab for the
treatment of Osteogenesis Imperfecta (OI) and alvelestat primarily
for the treatment of severe alpha-1-antitrypsin
deficiency-associated lung disease (AATD-LD). The Company’s
partner, Ultragenyx Pharmaceutical, Inc., has initiated a pivotal
Phase 2/3 pediatric study in young adults (5 to <26 years old)
for setrusumab in OI and a Phase 3 study in pediatric patients (2
to <7 years old) in the first half of 2023. The partnership with
Ultragenyx includes potential milestone payments of up to $245
million (following the recent $9 million milestone) and royalties
to Mereo on commercial sales in Ultragenyx territories. Mereo has
retained EU and UK commercial rights and will pay Ultragenyx
royalties on commercial sales in those territories. Setrusumab has
received orphan designation for osteogenesis imperfecta from the
EMA and FDA, PRIME designation from the EMA and has pediatric
disease designation from the FDA. Alvelestat has received U.S.
Orphan Drug Designation for the treatment of AATD, Fast Track
designation from the FDA, and positive data were reported from a
Phase 2 proof-of-concept study in North America, Europe and the UK.
In addition to the rare disease programs, Mereo has two oncology
product candidates in clinical development. Etigilimab (anti-TIGIT)
has completed enrollment in a Phase 1b/2 basket study evaluating
its safety and efficacy in combination with an anti-PD-1 in a range
of tumor types including three rare tumors and three gynecological
carcinomas - cervical, ovarian, and endometrial and is in an
ongoing Phase 1b/2 investigator led study at the MD Anderson Cancer
Center in clear cell ovarian cancer; navicixizumab, for the
treatment of late line ovarian cancer, has completed a Phase 1
study and has been partnered with OncXerna Therapeutics, Inc. in a
global licensing agreement that includes payments of up to $300
million in milestones and royalties.
For more information on Mereo BioPharma, please visit
www.mereobiopharma.com.
Ultragenyx Forward-Looking Statements and Use of Digital
Media
Except for the historical information contained herein, the
matters set forth in this press release, including statements
related to Ultragenyx's expectations and projections regarding its
future operating results and financial performance, business plans
and objectives for UX143, expectations regarding the tolerability
and safety of UX143, and future clinical and regulatory
developments for UX143 are forward-looking statements within the
meaning of the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995. Such forward-looking statements
involve substantial risks and uncertainties that could cause our
clinical development programs, collaboration with third parties,
future results, performance or achievements to differ significantly
from those expressed or implied by the forward-looking statements.
Such risks and uncertainties include, among others, the uncertainty
of clinical drug development and unpredictability and lengthy
process for obtaining regulatory approvals, the ability of the
company and Mereo BioPharma to successfully develop UX143, the
company’s ability to achieve its projected development goals in its
expected timeframes, risks related to adverse side effects, risks
related to reliance on third party partners to conduct certain
activities on the company’s behalf, the potential for any license
or collaboration agreement, including the company’s collaboration
agreement with Mereo to be terminated, smaller than anticipated
market opportunities for the company’s products and product
candidates, manufacturing risks, competition from other therapies
or products, and other matters that could affect sufficiency of
existing cash, cash equivalents and short-term investments to fund
operations, the company’s future operating results and financial
performance, the timing of clinical trial activities and reporting
results from same, and the availability or commercial potential of
Ultragenyx’s products and drug candidates. Ultragenyx undertakes no
obligation to update or revise any forward-looking statements. For
a further description of the risks and uncertainties that could
cause actual results to differ from those expressed in these
forward-looking statements, as well as risks relating to the
business of Ultragenyx in general, see Ultragenyx's Quarterly
Report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on August 4, 2023, and its subsequent periodic
reports filed with the SEC.
In addition to its SEC filings, press releases and public
conference calls, Ultragenyx uses its investor relations website
and social media outlets to publish important information about the
company, including information that may be deemed material to
investors, and to comply with its disclosure obligations under
Regulation FD. Financial and other information about Ultragenyx is
routinely posted and is accessible on Ultragenyx’s Investor
Relations website (https://ir.ultragenyx.com/) and LinkedIn website
(https://www.linkedin.com/company/ultragenyx-pharmaceutical-inc-/).
Mereo BioPharma Forward-Looking Statements
This press release contains “forward-looking statements.” All
statements other than statements of historical fact contained in
this press release 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
Mereo BioPharma’s 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 Mereo BioPharma’s
current expectations, beliefs and assumptions concerning future
developments and business conditions and their potential effect on
Mereo. While management believes that these forward-looking
statements are reasonable as and when made, there can be no
assurance that future developments affecting Mereo BioPharma will
be those that it anticipates.
All of Mereo BioPharma’s forward-looking statements involve
known and unknown risks and uncertainties some of which are
significant or beyond its control and assumptions that could cause
actual results to differ materially from Mereo BioPharma’s
historical experience and its present expectations or
projections.
Such risks and uncertainties include, among others, the
uncertainties inherent in the clinical development process; Mereo
BioPharma’s reliance on third parties to conduct and provide
funding for its clinical trials; Mereo’s dependence on enrollment
of patients in its clinical trials; and Mereo’s dependence on its
key executives. You should carefully consider the foregoing factors
and the other risks and uncertainties that affect Mereo BioPharma’s
business, including those described in the “Risk Factors” section
of its latest Annual Report on Form 20-F, reports on Form 6-K and
other documents furnished or filed from time to time by Mereo
BioPharma with the Securities and Exchange Commission. Mereo
BioPharma wishes to caution you not to place undue reliance on any
forward-looking statements, which speak only as of the date hereof.
Mereo BioPharma 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.
Contacts
Ultragenyx Pharmaceutical Inc.
InvestorsJoshua Higa415-475-6370ir@ultragenyx.com
MediaJeff Blake415-612-7784media@ultragenyx.com
Mereo BioPharma Group plc
Denise Scots-Knight, Chief Executive OfficerChristine Fox, Chief
Financial Officer+44 (0)333 023 7300
Burns McClellan (Investor Relations Advisor to Mereo)Lee Roth
+01 646-930-4406investors@mereobiopharma.com
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