On the 24th of October, OIFE hosted a webinar for the OI community about clinical trials and updates. 235 people from 52 countries signed up. Attendees were a mix of health professionals, scientists, OI clinicians, industry professionals, and individuals with OI and their family members. OIFE is excited to share this current OI study and research update with you.

The ORBIT & COSMIC studies – Ultragenyx

Ultragenyx is conducting two clinical studies, ORBIT and COSMIC, to investigate setrusumab (UX143), a monoclonal antibody, for the treatment of osteogenesis imperfecta (OI) in pediatric and young adults.

The objective of both ORBIT and COSMIC is to understand how setrusumab can safely and effectively restore bone production and reduce fracture risk. Setrusumab is hypothesized to block sclerostin, a protein that slows the process of bone forming. It is thought that blocking sclerostin will allow increased bone formation and stronger bones, which in turn might reduce fracture risk.


Phase II/III study
The purpose of the ORBIT study is to assess dose, efficacy and safety of setrusumab vs. placebo.

  • This study is currently enrolling patients aged 5 to <26 years
  • Individuals must have a confirmed genetic (COL1A1 or COL1A2) diagnosis of Type I, III or IV OI
  • Must be willing to not receive bisphosphonate therapy during the study*

*Individuals are expected to stop bisphosphonate use during this study, so that solely the effect of setrusumab can be analyzed. The use of multiple medications that impact bones make it difficult to interpret results. Learn more about this study here.

Ultragenyx announces promising interim data from Phase II Orbit study

In their press release on October 14, 2023, Ultragenyx announced that treatment with setrusumab reduced incidence of fractures in patients with OI by 67% following at least 6 months of treatment and demonstrated improvements in lumbar spine bone mineral density (BMD).



Phase III study
The purpose of the COSMIC study is to evaluate the efficacy of setrusumab versus IV against intravenous bisphosphonates (IV-BP) in children with OI.

  • This study is currently enrolling patients aged 2 to <5 years
  • Individuals must have a confirmed genetic (COL1A1 or COL1A2) diagnosis of Type I, III or IV OI
  • Prior/current exposure to bisphosphonate therapy

Learn more about this study here. To learn more about Ultragenyx research, reach out via email, OIStudyInfo@ultragenyx.com.


Poise 1 (Sanofi)

TGF-β Inhibition for the Treatment of Osteogenesis Imperfecta

Sanofi is conducting an early phase study in adults with OI Types I and IV with an anti-TGFb antibody called SAR439459. This study is called Poise 1 and is a Phase 1 study, where the researchers evaluate the treatment’s safety and determine a safe dosage range.

Inclusion criteria:

  • Male or female between 18 and 65 years old, with the exception of post- menopausal women
  • Confirmed diagnosis of Osteogenesis Imperfecta Types I or IV, including documented genetic mutation in the COL1A1 or COL1A2 genes. Sanofi will provide OI-specific genotyping if it is not already in the patient’s medical history.
  • Have experienced ≥ 2 bone fractures since the age of 18 OR at least 1 bone fraction in the last 10 years.

This study involves a single administration of SAR439459 given intravenously (IV) into the arm, with a 6-month follow period. At this early stage in development, Sanofi is recruiting a limited range of study participants, but they will consider expanding enrollment criteria in future studies. Participants in the Poise 1 study are not likely to experience benefits from SAR439459, and 25% will receive a placebo, but all participants will help with the scientific understanding of OI and SAR439459 as we prepare for future long-term studies. The assessments in this study include digital, non-invasive strategies to better understand how OI patients move and are active throughout the day as well as direct patient feedback on daily activity and pain.

TGFb is a signaling molecule, which is a way cells communicate and coordinate with each other. Specifically, it is an important part of the bone remodeling environment, playing a role in the balance of forces which remove and build new bone. It even has a role in pain. In OI, signaling related to TGFb is dysregulated, so controlling that signaling with SAR439459 may be a way to influence symptoms caused by OI.

Study participants will be compensated for their travel and accommodation associated with visits to the study site. Such travel and accommodation can be arranged directly by Sanofi or a third-party service provider appointed by Sanofi.

For this early study, our two sites in Europe are located in France. The other sites are in the US, Canada and Australia. Additional information on participating study sites and how to contact Sanofi, if interested, is available under ClinicalTrials.gov NCT05231668.

The TOPAZ Trial

Treatment of Osteogenesis Imperfecta with Parathyroid hormone and Zoledronic acid

TOPaZ is the largest study performed so far in osteogenesis imperfecta with 350 participants. The purpose of the TOPaZ Trial is to investigate whether a two-year course of teriparatide (TPTD) followed by antiresorptive therapy with a single infusion of zoledronic acid (ZA) in adults with OI reduces the risk of fracture as compared with standard care. Teriparatide is effective at increasing bone mineral density (BMD) in OI and Zoledronic acid is hypothesized to be able maintain a new bone after it has been formed. Almost anyone >18 with a clinical diagnosis of OI is eligible.

See more information on the project webpage.


BOOSTB4 Update

Boost Brittle Bones Before Birth (BOOSTB4) is a research study investigating the possibility of using highly bone forming fetal mesenchymal stem cells (fMSC) as a treatment of severe OI. The treatment involves transplanting the stem cells into the baby affected with OI during pregnancy or soon after birth. The main aim of the BOOSTB4 clinical trial is to test whether the treatment is safe and effective.

The BOOSTB4 study has completed participant recruitment. In the primary follow-up of patients, no serious or adverse events were observed, the treatment was deemed safe after multiple i.v. booster doses, no immune response to the mismatched fetal-MSC occurred and only minimal pain was reported.

See more information at the project webpage or at clinicaltrials.gov.

Project Saturn

Project Saturn is a real-world evidence and data collaboration with existing European datasets of osteogenesis imperfecta to support future therapies and answer specific research questions.

For the timely and sustainable availability of therapies, the agreement of stakeholders is necessary. These stakeholders are Regulators (ETA), Health Technology Assessments (HTAs), and Payers. The size of clinical studies for rare diseases is usually limited (+/- 200 patients). Health Technology Assessors (HTAs) and Payers would likely need to see more evidence/data before granting access and making therapies available long-term.

The objective of Project Saturn is to meet the data needs of all stakeholders, to ensure they have the evidence to support the decision to make a potential therapy available to patients and to converse with data stakeholders to understand what data is needed. This in turn, will make new therapies available to the people who need them.

Find out more by contacting Mereo Biopharma.