Mereo BioPharma Announces Phase 3 ORBIT and COSMIC Results for Setrusumab (UX143) in Osteogenesis Imperfecta
Rhea-AI Summary
Mereo BioPharma (NASDAQ: MREO) announced Phase 3 results for setrusumab (UX143) in Osteogenesis Imperfecta on Dec 29, 2025. Both Phase 3 studies, ORBIT and COSMIC, failed to meet their primary endpoint of reducing annualized clinical fracture rate versus placebo or bisphosphonates. Both studies did achieve their secondary endpoints: statistically significant improvements in bone mineral density (BMD). No change in the safety profile was observed. The company reported a $48.7M cash balance at end-Q3 2025 and announced immediate reductions in pre-commercial and manufacturing activities while pursuing further data analyses and partnering for alvelestat.
Positive
- BMD improvements statistically significant in ORBIT and COSMIC
- No change in safety profile observed across studies
- $48.7M cash balance at end of Q3 2025
Negative
- Both Phase 3 studies failed primary endpoint: no significant fracture-rate reduction
- Pediatric COSMIC fracture reduction did not reach statistical significance
- Immediate reductions in pre-commercial and manufacturing activities to conserve cash
News Market Reaction
On the day this news was published, MREO declined 87.65%, reflecting a significant negative market reaction. Argus tracked a trough of -48.1% from its starting point during tracking. Our momentum scanner triggered 26 alerts that day, indicating elevated trading interest and price volatility. This price movement removed approximately $2.61B from the company's valuation, bringing the market cap to $368M at that time. Trading volume was exceptionally heavy at 91.4x the daily average, suggesting significant selling pressure.
Data tracked by StockTitan Argus on the day of publication.
Key Figures
Market Reality Check
Peers on Argus
Biotech peers showed mixed moves, with names like OMER at -4.20% while others were positive, indicating stock-specific rather than broad sector dynamics.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Nov 10 | Q3 2025 earnings | Neutral | -1.7% | Reported Q3 results, cash runway to 2027, and flagged Phase 3 catalysts. |
| Aug 19 | Licensing deal | Positive | -2.4% | Exclusive global licensing of vantictumab for rare bone disorder ADO2. |
| Aug 12 | Q2 2025 earnings | Positive | +9.2% | Strong cash position and continued advancement of Phase 3 setrusumab trials. |
Recent news flow shows mixed price responses: a strong positive move on Q2 earnings, a negative reaction to a licensing deal, and a mild dip on Q3 results.
Over the past few quarters, Mereo highlighted cash resources of $48.7M–$56.1M and a runway into 2027, while advancing Phase 3 setrusumab trials in osteogenesis imperfecta and managing a portfolio of partnered assets. The Q2 2025 update, with progress in Phase 3 studies, saw a +9.21% move, while a vantictumab licensing deal and Q3 results both saw modest declines. Today’s Phase 3 outcome on setrusumab follows those long-flagged readouts, marking a key inflection in that program’s trajectory.
Market Pulse Summary
The stock dropped -87.7% in the session following this news. A negative reaction despite some positive secondary endpoints fits a narrative where investors focus on missed primary fracture endpoints in both ORBIT and COSMIC. Previous events saw a -2.38% move on a positive licensing deal and modest pressure on Q3 results, suggesting occasional downside even on constructive updates. With cash at $48.7M and management signaling cuts to pre-commercial spend while reassessing the program, attention would likely shift to pipeline optionality and partnering progress.
Key Terms
phase 3 medical
osteogenesis imperfecta medical
bone mineral density medical
bisphosphonates medical
annualized clinical fracture rate medical
AI-generated analysis. Not financial advice.
Neither study achieved its primary endpoint of reduction in annualized clinical fracture rate compared to placebo (ORBIT) or bisphosphonates (COSMIC)
Both studies achieved secondary endpoint of improvements in bone mineral density with strong statistical significance
LONDON, Dec. 29, 2025 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO) (“Mereo” or the “Company”), a clinical stage biopharmaceutical company focused on rare diseases, today announced results from the Phase 3 ORBIT and COSMIC studies for setrusumab (UX143) in Osteogenesis Imperfecta (OI). Neither study achieved statistical significance against the primary endpoints of reduction in annualized clinical fracture rate compared to placebo or bisphosphonates, respectively. Both studies achieved their secondary endpoints of improvements in bone mineral density (BMD) against comparators (placebo and bisphosphonates) with strong statistical significance. There was no change in the safety profile observed.
“Whilst we are disappointed by these results, we will be conducting additional analyses on the data, to assess next steps and the best path forward for the program, especially in pediatrics given the totality of the data and lack of other treatment options for individuals with OI. In the meantime, we are carefully managing our cash resources with immediate reductions in our pre-commercial and manufacturing activities, and we are continuing to advance partnering discussions for alvelestat,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo.
ORBIT and COSMIC bone mineral density (BMD) improvements
In the ORBIT study, participants experienced statistically significant and substantial improvements in BMD compared to placebo, at levels consistent with the treatment effect observed in Phase 2 studies. These BMD changes were not accompanied by a corresponding reduction in annualized fracture rates and there was a low fracture rate in the placebo group.
In the pediatric COSMIC study, patients had a substantially higher baseline fracture rate compared to the patients enrolled in ORBIT. In this younger patient population, meaningful improvements in BMD were associated with a reduction in annualized fracture rate for setrusumab treated patients over bisphosphonate treated patients, though the reduction did not meet statistical significance.
Additional analyses on the data across both studies are being conducted, including in other bone health and clinical endpoints beyond fractures.
Mereo’s cash balance was
- Alvelestat for AATD-lung disease – in partnering discussions
- Vantictumab for osteopetrosis – partnered with āshibio
- Leflutrozole for male infertility – partnered with ReproNovo.
About the Setrusumab Phase 3 Program
Ultragenyx is developing setrusumab in pediatric and young adult patients across OI sub-types I, III and IV with two late-stage studies: the pivotal Phase 2/3 Orbit study and Phase 3 Cosmic study.
The global, seamless Phase 2/3 Orbit study is evaluating the effect of setrusumab on clinical fracture rate in patients aged 5 to 25 years. The pivotal Phase 3 portion of the study enrolled 159 patients at 45 sites across 11 countries, with subjects randomized 2:1 to receive setrusumab or placebo, and a primary efficacy endpoint of annualized clinical fracture rate.
The global Phase 3 Cosmic study evaluated the effect of setrusumab on reduction in annualized fracture rate in patients aged 2 to <7 years compared to bisphosphonates. The Cosmic study has enrolled 69 patients at 21 sites across 7 countries with patients randomized 1:1 to receive setrusumab or intravenous bisphosphonates (IV-BP) therapy.
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.
About Osteogenesis Imperfecta (OI)
Osteogenesis Imperfecta (OI) includes a group of genetic disorders impacting bone metabolism. Approximately
About Mereo BioPharma
Mereo BioPharma is a biopharmaceutical company focused on the development of innovative therapeutics for rare diseases. The Company has three rare disease product candidates: setrusumab for the treatment of osteogenesis imperfecta (OI); alvelestat for the treatment of alpha-1 antitrypsin deficiency-associated lung disease (AATD-LD) and vantictumab for the treatment of autosomal dominant osteopetrosis type 2 (ADO2). The Company’s partner for setrusumab, Ultragenyx Pharmaceutical, Inc., has reported results from the Phase 3 portion of a pivotal Phase 2/3 study in pediatrics and young adults (5 to 25 years old) for setrusumab in OI and in the Phase 3 study in pediatric patients (2 to <7 years old). The partnership with Ultragenyx includes potential additional milestone payments of up to
Forward-Looking Statements
This press release contains “forward-looking statements” that involve substantial risks and uncertainties. All statements other than statements of historical fact contained herein are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended, and Section 21E of the United States Securities Exchange Act of 1934, as amended. 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.
All of the Company’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 the Company’s historical experience and its present expectations or projections. Such risks and uncertainties include, among others, the uncertainties inherent in the clinical development process; the Company’s reliance on third parties to conduct and provide funding for its clinical trials; the Company’s dependence on enrollment of patients in its clinical trials; and the Company’s dependence on its key executives. You should carefully consider the foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in the “Risk Factors” section of its Annual Report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in the Company’s subsequent filings with the Securities and Exchange Commission. 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 Denise Scots-Knight, Chief Executive Officer Christine Fox, Chief Financial Officer | +44 (0)333 023 7300 |
| Burns McClellan (Investor Relations Adviser to Mereo) Lee Roth | +01 646 930 4406 |
| Investors | investors@mereobiopharma.com |
FAQ
What did Mereo (MREO) announce about setrusumab on December 29, 2025?
Did the ORBIT and COSMIC studies for MREO show safety concerns for setrusumab?
How did setrusumab perform on bone mineral density in the Phase 3 MREO studies?
What is Mereo's reported cash position and near-term cost actions after the Phase 3 results?
Will Mereo pursue further analysis or development for setrusumab (MREO)?
