BPS-804 (setrusumab) is a fully human monoclonal antibody designed to inhibit sclerostin, thereby improving bone strength and therefore reduce fractures in patients with osteogenesis imperfecta (OI) and improve quality of life.
OI is a rare genetic disorder, commonly known as brittle bone disease, which is characterized by fragile bones that fracture easily. In addition to fractures, individuals with OI often have muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, and short stature. The majority of cases of OI (up to 90 %) are caused by a dominant mutation in the genes coding for type I collagen, a key component of healthy bone. Current treatment of OI is based on supportive care, focusing on treating fractures and maximizing mobility. To date, there are no FDA or EMA approved treatments.
We recently announced the results of our Phase 2b study for setrusumab in adults, designed to evaluate 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. This was the first time this technique had been used in an OI trial. More well-recognised techniques were 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 study enrolled 112 patients in the US and Europe into 3 blinded dose-ranging arms and an open-label arm at the top dose. The open-label arm already reported six-month open-label data on the top dose on 30 May 2019. The top-line 12-month data from the other three blinded dose-ranging arms of the study were reported on 11 November 2019. 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.
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.
The trial did not show sustained 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.
We are now preparing to move forward with our pivotal, Phase III trial, which we hope, once completed, will allow us to file for registration with the regulatory authorities. The European Medicines Agency (EMA) has approved our European Paediatric Investigation Plan (PIP), which foresees the trial being run in approximately 165 children with severe OI, aged 5-18 years old. This pivotal trial has fractures and fracture reduction as its primary endpoint. Going forward, we also intend to talk with the FDA, the US regulatory authority, to understand how we might also run the trial in the USA.
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. It 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.
Bringing the patient perspective into our work
Nothing about us without usAlastair Kent OBE, AMBASSADOR, GENETIC INTEREST GROUP, UK
Mereo is committed to developing and making available therapies in collaboration with all stakeholders, most importantly, the people who we are seeking to serve. This means that we are committed to ensuring that the patient voice is included in every step of the way; and we actively seek opportunities for having leadership from the OI community as part of our development programme for setrusumab.
Rare diseases, individually, each affect small numbers of people. This means that patients are rare but it also means that expertise and experience is rare, too. A primary care physician might never see one case of a given rare disease. Patients and their families, on the other hand, are often extremely well-informed – more often than not becoming experts in their condition. This means that their point of view and their experience is crucially important in all decision-making, because they have the lived experience and are able to point to what will make a real and meaningful difference in their lives.
The respect for and inclusion of the rare disease patients’ point of view is also recognised by Regulatory, Health Technology Assessment and Pricing & Reimbursement authorities, who are increasingly including patient representation in their evaluation and decision-making processes, both in the USA and in Europe. Mereo is committed to maximising those opportunities to include the patient voice, while respecting the independence of patient representatives and community leaders. Conflict of interest policies and procedures are in place to respect the different roles and responsibilities of all actors in such processes and Mereo adheres to these. We also make available all financial support that we provide to patient organisations via our transparency reporting.
Multi-stakeholder collaboration is a fundamental condition to achieving patient access to rare disease medicinesEURORDIS MULTI-STAKEHOLDER FORUM, FEBRUARY 2019
In addition to the formal external engagements, we also believe that it is important for all of our team members at Mereo to be able to feel and understand the potential benefits that our shared work is providing for patients. We are proud that organisations from the Osteogenesis Imperfecta community spend time with our broad company team in order to secure that we are always keeping the patient perspective in our minds.
Osteogenesis Imperfecta Community Representation Organisations
RARE DISEASE ORGANISATIONS
1. Shapiro J (2014) Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease.community
Academic Press. Chapter 2: p15-22
2. Glorieux et al (2017) BPS-804 Anti-Sclerostin Antibody in Adults With Moderate
Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial. JBMR 32: 1496-1504