Category: Updates from the OIF

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

Participate in OI Research!

As you know, supporting research is an important part of the OI Foundation’s mission and we need volunteers to help advance the scientific understanding of OI so that more and better treatments can be made available to the OI community.  The OI Foundation shares information about current research and studies through emails to those who are signed up for the OI Registry. To receive these updates and help move OI research forward, please join the OI Registry!

If at any point you have questions, please contact the OIF at bonelink@oif.org or 301-947-0083.

OI Studies (Currently Recruiting) 

Disclaimer: The OI Foundation is not involved in the design or management of this research, and as such, is neither endorsing nor supporting these studies. The mission of the OIF is to keep the OI community informed of all relevant studies. This information is made available as a service to the OI community.

7707: Use of clear aligners for the treatment of dental malocclusion in individuals with Osteogenesis Imperfecta Types III and IV (Brittle Bone Disorders Consortium)

 The purpose of this study is to determine if it is safe to use Invisalign clear aligners in correcting the misalignment of teeth in people with OI. Clear aligners are transparent plastic trays that are designed to fit over your teeth.

You may be eligible to participate if you:

• are between ages 12 – 40
• have OI type III or IV
• have had no prior orthodontic treatment

Please find more information here.

7708: Cardiopulmonary Outcomes in Osteogenesis Imperfecta

The purpose of this study is to understand the cause of the restrictive pulmonary physiology in the OI population. Respiratory insufficiency is the leading cause of death in patients with OI.

You may be eligible to participate if you:

• are 18 years or older
• have been diagnosed with OI clinically and/or genetically
• have no cardiopulmonary comorbidities that affect lung compliance

Please find more information here.

Ultragenyx ORBIT Study

The purpose of this study is to investigate the efficacy and safety of setrusumab in pediatric and young adult patients with OI Types I, III, or IV.

Inclusion criteria:

• 5-25 years
• Confirmed diagnosis of OI Types I, III, or IV
• Are willing to NOT receive bisphosphonate therapy during the study.
• Had at least one fracture in the past year or at least two fractures in the past 2 years.

Learn more about this study here. To find out more about Ultragenyx studies, click here.

Ultragenyx COSMIC Study

 The purpose of this study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants.

Inclusion criteria:

• 2-4 years
• Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2
• Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI

Learn more about this study here. Please reach out to trialrecruitment@ultragenyx.com if you are interested in participating.

Poise 1 (Sanofi)

The purpose of this study is to deepen the scientific understanding of OI and the anti-TGFb antibody SAR439459, as we prepare for future long-term studies. The study also includes digital, non-invasive strategies to better understand how OI patients move and are active throughout the day. All participants will be reimbursed for travel and accommodations involved in visiting study sites during the study duration, including airfare for those who are not within driving distance of a study site.

Inclusion criteria:

• Male or female between 18 and 65 years old, with the exception of postmenopausal 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 fracture in the last 10 years.

To learn more about this study, please review the study brochure.

Updates from the OIF

OIF Scientific Meeting Recap

Each year during the OI Foundation’s annual Scientific Meeting, leading scientists and medical professionals gather to share their research on osteogenesis imperfecta (OI). Dr. Frank Rauch (OIF Medical Advisory Council Member) discussed the 2023 meeting and some of the major takeaways from this year’s event in a Research Update video.

Results from the Pain and OI Survey

In the past few years, researchers have been putting more focus on understanding how pain impacts people with OI. While pain has a large impact on people’s lives, it is unclear how it specifically impacts aspects of a person’s well-being and health.

The Pain and OI Project, a group co-led by the OI Foundation and the Osteogenesis Imperfecta Federation of Europe (OIFE) created a survey where all adults with OI could share information about their pain and how it impacted them. This group consists of international OI advocacy leaders, researchers, and medical professionals from 12 different countries. This survey gives a snapshot of a group of adults with OI, and may help contextualize an individual’s experience and suggest future areas of study for more research.

Below are some major initial findings from the survey, and the OIF hopes to present a more thorough analysis later.

1. Many people with OI appear to experience lots of chronic pain.
2. Back pain is common for people who completed the survey.
3. Pain impacts many parts of people’s lives including career and social life decisions.

What’s next?   

Pain and OI, like our understanding of OI itself, is complex. We hope that the results from this survey can help contextualize the pain that OI community members feel, and that it can help drive further research.

In-depth survey results will be shared in the June issue of the OIF’s Breakthrough newsletter.

Learn more about the Pain and OI project at https://oife.org/what-we-do/pain-oi/.

OI Foundation Resources: 

Current OI Studies and Publications

The OI Foundation’s Current OI Studies and Publications page features a list of OI studies that are currently recruiting, as well as a collection of published OI research.

What You Need to Know about Clinical Trials 

The OI Foundation’s What You Need to Know about Clinical Trials factsheet defines major terms and stages of clinical trials, explains the role of the FDA, and answers common questions. This and other OIF factsheets are available on the OIF website’s Information Center at www.oif.org/factsheets.

Current State of OI Research Video Series 
The OI Foundation’s Current State of OI Research video series was created to highlight and describe the work of the Brittle Bone Disorders Consortium (BBDC), a multicenter initiative that focuses on understanding and providing better treatment options for osteogenesis imperfecta. To watch recordings of these sessions, click here.