Category: Research

We are pleased to share exciting news from our partners at Ultragenyx. They have completed enrollment for their Phase 2/3 Orbit and Phase 3 Cosmic studies. These studies evaluate setrusumab (UX143) in both pediatric and young adult patients with osteogenesis imperfecta (OI).

“We would like to thank the OI community for its support, trust and participation as we complete this important step in the advancement of the setrusumab program,” said Eric Crombez, M.D., chief medical officer at Ultragenyx.

For more information about the studies and what this development means for our community, please visit https://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-announces-completion-enrollment-phase-3-orbit-and

The OI Foundation recently shared an announcement from Ultragenyx which shared Interim data from the Phase 2 portion of their Orbit study. This data showed 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). CLICK HERE TO READ THE FULL PRESS RELEASE

Ultragenyx is now enrolling participants for the Phase III of this trial. The trials are open to children with Types I, III, and IV OI and have sites around the country.

Dr. Alison Skrinar (Ultragenyx) joined OIF Board Member Dr. Michelle Fynan to discuss setrusumab and the clinical trial process in a video for the OI community. Please take a minute to watch this video at https://www.youtube.com/watch?v=kUYp3REcO2g

Participate in the OI Wellbeing Study

Baylor College of Medicine is conducting this OI Wellbeing Study as a part of the Brittle Bone Disorders Consortium which aims to improve the lives of people with Osteogenesis Imperfecta.
This study addresses an under-researched aspect of health critical to the wellbeing of the OI community, namely psychological health. Participants will meet with a researcher over a secure teleconference platform for about 1 hour and complete a series of questionnaires about mental health, physical health, quality of life, social wellbeing, and experience with health care professionals. Participants are compensated $50.

This information may help develop psychological interventions personalized for people with OI. Please share information about this study with any adult with OI that you believe may be interested in participating.

If you have any questions about the study or are considering participating, please email OIWellbeing@bcm.edu or call (713) 798-0117.

From the BBDC: Osteogenesis Imperfecta Over Time: What We’re Learning from a Natural History Study
To learn more about the natural history of individuals with osteogenesis imperfecta (OI), the Brittle Bone Disorders Consortium (BBDC) is conducting a “Longitudinal Study of Osteogenesis Imperfecta.” The team is performing a long-term follow-up of a large group of people with OI to investigate vertebral compression fractures of the spine, scoliosis (curvature of the spine), dental health, and more.

Click here to learn more!

The Michael Geisman Fellowship Grant program awards funding to post-doctoral trainees who are currently working on projects with clear relevance to osteogenesis imperfecta (OI), or who have projects that will enable them to develop expertise in OI research.

Applicant Requirements:

• Applicant must hold an MD, DDS, DO, or PhD, and be appointed at the level of a post-doctoral trainee, or equivalent, within an academic institution.
• Applicant should have completed their Ph.D. or clinical training within the past five (5) years.

Fellowship Guidelines:

• Michael Geisman Fellowship awards provide up to $50,000 per year. It is the intention of the OI Foundation that grant monies be used to fund actual costs related to the research being performed including Fellow salary, fringe benefits, and supplies.
• Fellowship awards are for one year; a second year of funding may be approved based upon satisfactory performance during the first year of funding.
• Research must be done under the supervision of mentor with training and experience in osteogenesis imperfecta research or research in a related field.

How to Apply:

1. Complete application
2. Mentor of applicant must submit a copy of his/her biosketch and a letter of recommendation on behalf of the trainee, which also confirms that the mentor will supervise the trainee’s research.
3. Applications require two additional letters of recommendation from scientists or clinicians who can comment upon the applicant’s training, ability, and potential to develop expertise in OI research.
4. Submit application, reference letters, and mentor biosketch as PDF documents to sconnors@oif.org NO LATER THAN October 23, 2023.

If you have any questions, please contact Stacie Connors at sconnors@oif.org.

OI Research Update:

Abnormal lung function in osteogenesis imperfecta due to both intrinsic and extrinsic causes
Gochuico et al. (2023) J Med Genet May 16:jmg-2022-109009. Doi:10.1136/jmg-2022-109009

Lung disease is the major cause of illness and death in individuals with osteogenesis imperfecta (OI), a collagen-related bone fragility disorder. Previously, external factors such as scoliosis and chest wall deformities were considered responsible for abnormal lung function in OI. Prior data from the NIH USA OI Research Program lead by Dr Joan Marini showed that pulmonary function declined with age even in children who did not have scoliosis, suggesting an intrinsic component for OI lung disease (Thiele et al, Human Mol Genet. (2012) 21(16):3535-45), that is, a defect directly in the respiratory system itself.

In this investigation, we studied 37 children and young adults with several types of OI, 29 of whom have structural mutations in type I collagen. Type I collagen is a component of lung parenchyma as well as the major matrix protein of bone. Study participants underwent lung function tests, X-Rays and CTs of lung tissue. Most patients had restrictive lung disease and decreased gas exchange, independent of scoliosis. Analysis of chest scans and breathing tests showed thickening of the walls of small airways and lung tissue abnormalities.  We conclude that OI also causes intrinsic lung disease that negatively impacts Quality of Life (QOL) in OI. Further study of intrinsic lung abnormalities may lead to improved treatment options and improve QOL.

Click here to view the full article.

Ultragenyx Pharmaceutical Inc. and Mereo BioPharma Group today announced data from the dose-selection Phase 2 portion of the Phase 2/3 Orbit study, showing that setrusumab significantly  increased bone production in OI-affected patients after only 3 months.

Click here to read the full article.

On June 5th, the Foundation received the following communication from Ultragenyx regarding the interim data of their Phase 2 study, Orbit.

Dear OI Advocates,

As our trusted partner in OI, we are excited to share with you an important update about the Orbit study, NCT05125809, on behalf of the Ultragenyx OI study team. As you may be aware, Ultragenyx is sponsoring Orbit, a global study to determine the safety and efficacy of setrusumab, UX143, in the treatment of OI. Setrusumab is a fully human monoclonal antibody that inhibits sclerostin. Sclerostin is a protein that causes decreased bone formation and increased bone resorption. By inhibiting sclerostin, the goal of setrusumab is to increase bone formation, strength and bone mineral density and, to a lesser extent, decrease bone resorption.

Orbit is a randomized double-blind placebo-controlled Phase 2/3 study in OI types I, III, IV patients aged 5 to <26 (N=219). Enrollment in the Phase 2 portion of the study was completed in February with 24 patients. Patients received setrusumab at one of two doses to determine the optimal dosing strategy for Phase 3. We are pleased to announce the interim results from Phase 2 portion of the Orbit study. Data from the pediatric cohort suggests a substantial benefit on bone formation within 3 months on setrusumab.

Across all patients evaluated, setrusumab significantly increased levels of serum P1NP, a marker of bone formation, and a significant and rapid bone-building effect in the lumbar spine. There have been no treatment-related serious adverse events observed in the study. Reported adverse events have been consistent with the anticipated safety profile for setrusumab based on previous trial and include infusion-related reactions, headache, and sinusitis. There were no safety-related differences observed between dosing groups or age groups. “It’s encouraging to see similar lumbar spine bone mineral density results at 3 months in children to what we saw in adults at 12 months using the same dose levels,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We believe it suggests that growing bones are more dynamic, and we anticipate a greater effect on bone formation and strength in the younger subjects with immature skeletons.”

Having this data allows Ultragenyx to move forward to the pivotal Phase 3 portion of the global study. Phase 3 will include approximately 195 participants, randomized 2:1 to receive setrusumab or placebo. We are grateful to the patients, parents, and caregivers who contributed to this study. We couldn’t do any of this work without the support from the OI community! To learn more about Patient Advocacy at Ultragenyx and our commitment to the OI community, including the upcoming Phase 3 trial, please visit https://ultrarareadvocacy.com/conditions-we-study/osteogenesis-imperfecta-oi/ or reach out via patientadvocacy@ultragenyx.com.

Thank you all for your support and trust in this work.

Sincerely,
Jenny McCue
Jenny McCue, Executive Director OI patient advocacy and engagement