OI (commonly known as brittle bone disease) is a serious, rare genetic disorder caused by a problem in the formation of type I collagen, and characterized by fragile bones that fracture easily, often starting from birth. It can affect people’s lives in a multitude of ways, from frequent fractures and skeletal deformities to constant chronic pain, respiratory insufficiency and hearing loss. And each person’s experience is different.

Ingunn Westerheim, President of OIFE, shares her experiences of life with Osteogenesis Imperfecta in an April 2020 interview.

How is OI treated?

There are currently no FDA- or EU-approved treatments for OI. Current treatment is based on supportive care, using off-label, unapproved compounds to seek to improve bone density, treating fractures as they occur – an often all-too-frequent occurrence particularly in children with OI – and on maximizing mobility via physiotherapy, pain management and orthopaedic surgery.

The majority of cases of OI (up to 90%) are caused by a dominant mutation in the genes coding for – Type I collagen – which is a key component of healthy bone.  As Setrusumab aims to act on dual pathways for both bone formation and bone resorption, our clinical studies are seeking to understand if Setrusumab can play a role in improving the health and quality of life for people with OI.

OI is recognized as an area of high unmet medical need.  Setrusumab (BPS-804) has been designated an “Orphan Drug” in the USA and the EU, meaning it is officially acknowledged by the regulatory authorities to be targeting a rare and serious disease.  Most recently, Setrusumab has been granted Rare Pediatric Disease Designation by the FDA. This means that the FDA formally recognises the significant unmet medical need in children.  In addition, Setrusumab has also been granted PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA), a programme aimed at enhancing support for the development of medicines that target an unmet medical need; as well as being accepted in the EMA’s Adaptive Pathways programme.

Clinical Status

Setrusumab has been studied in adults with OI and, in 2019, we announced the results of our Phase 2b study for Setrusumab in adults.

This was designed to evaluate whether Setrusumab was able to create an increase in bone density measured by High-Resolution peripheral Quantitative Computed Tomography (HRpQCT), a relatively new imaging technique that allows the examination of the microarchitecture of the bone in a non-invasive manner.

The study in adults with OI enrolled 112 patients in the US and Europe into three blinded dose-ranging arms and an open-label arm at the top dose.   The top-line 12-month data from the three blinded dose-ranging arms of the study were reported on 11 November 2019, with a further update in January 2020.  These demonstrated Setrusumab to have a dose-dependent bone-building activity measured by DXA scans as well as data showing a trend in fracture reduction when given at the highest dose in the study.  The data also demonstrated such activity across all types of OI that were studied in the trial:  Types I, III and IV.

Further the data published on 14 January 2020 showed Setrusumab to have a positive impact on bone stiffness and strength as measured by Finite Element Analysis (FEA).

Setrusumab was demonstrated to be safe and well-tolerated in the patients participating in the Phase 2b adult study, as well as by the 83 subjects who have received it across the 4 Phase 1/2 studies completed to date.

This was the first time that HRpQCT had been used in an OI trial.  More well-recognized techniques were also used for the secondary endpoints, which included the traditional and well-established DXA scan, measuring bone density; as well as fractures and quality of life, amongst other aspects of OI.

The trial did not show a statistically significant increase in the trabecular bone measured by the HRpQCT imaging, because of the high variability of the baseline bone in the studied patients, which fell far outside the values expected from the literature published to date.  We will be sharing the findings about HRpQCT as a technique with the research community to continue to build understanding of the role of HRpQCT as a measurement in bone research.

Following the review of the data from the Company’s Phase 2b ASTEROID study, Setrusumab was partnered with Ultragenyx (NASDAQ:RARE) for further development. Ultragenyx are leading the global clinical development of setrusumab, supported by Mereo. Mereo retains rights to commercialization in Europe/EEA and UK. Setrusumab has entered a registrational Phase 2/3 study in 5-25 year olds in Q2:2022. A supportive pediatric study in 2-5 year olds is due to initiate in late 2022.

Scientific Publications

• Glorieux F. et al. 2017. BPS-804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial., J Bone Miner Res, 32: 1496-1504.
• Shapiro J. 2017. Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease, Community Academic Press. Chapter 2: p15-22