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Mereo BioPharma's Setrusumab Demonstrates Dose-Dependent Bone Building and Trend in Fracture Reduction in Phase 2b ASTEROID Study in Adults with Osteogenesis ImperfectaDose-Dependent and Statistically Significant Improvement in Areal Bone Mineral Density (BMD) Over Baseline at the Lumbar Spine, as Measured by DXA, Reaching 8.8% at 12 Months in Highest Dose Cohort (p<0.001); Improvement Consistent Across All OI Subtypes Represented in Study Trend of Decrease in Fractures Observed in Highest Dose Cohort Results Support Progression of Setrusumab into Pediatric Pivotal Study in OI as Planned Setrusumab was Safe and Well-Tolerated; No Cardiac-Related Safety Concerns Observed in the Study Conference Call Today at 8:00 a.m. EST / 1:00 p.m. GMT LONDON and REDWOOD CITY, Calif., Nov. 11, 2019 (GLOBE NEWSWIRE) -- Mereo BioPharma Group plc (NASDAQ: MREO, AIM: MPH), "Mereo" or the "Company" or the "Group," today announces 12-month topline data from the Company's Phase 2b dose-ranging "ASTEROID" clinical study of setrusumab (BPS-804), an anti-sclerostin antibody, in adults with Type I, III or IV osteogenesis imperfecta (OI), a rare bone disease with no approved treatments. ASTEROID was the largest, prospectively-designed, interventional clinical study to be performed in this patient group. The primary endpoint of the ASTEROID study was change in Trabecular Volumetric Bone Mineral Density (Tr vBMD) of the radius (wrist) over baseline after 12 months of treatment as measured by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). As a result of the unexpected high heterogeneity of the study patients’ trabecular bone baseline values at the wrist (including both very low and very high trabecular bone at baseline as compared to the literature1), the primary endpoint was not met at any of the three setrusumab dose levels. HR-pQCT is a relatively new imaging technique that has not been used widely in clinical studies and was chosen in order to improve the understanding of the effect of setrusumab on the bone biology in OI patients, given it can measure both trabecular and cortical vBMD separately. Importantly, an increase in total vBMD at the wrist as measured by HR-pQCT (measuring cortical and trabecular together), a secondary endpoint of the study, was observed and reached statistical significance in the medium and high dose cohorts. Mean increases in total vBMD were 4.11% (p=0.004), 4.5% (p=0.028), and 0.58% (p=0.97) in the high, medium, and low dose cohorts, respectively. This suggests total vBMD increases were driven by the ability of setrusumab to increase cortical vBMD. The study achieved its important secondary endpoint of increase in areal Bone Mineral Density (BMD) at the lumbar spine at 6 and 12 months over baseline using two-dimensional dual-energy X-ray absorptiometry (DXA), a well-established measurement tool of BMD (cortical + trabecular bone), reaching statistical significance in the high and medium doses cohorts at both 6 and 12 months with a clear dose-dependent response. Mean increases in areal BMD at the lumbar spine were 8.8% (p<0.001), 6.8 % (p<0.001), and 2.6% (p=0.057) in the high, medium, and low dose cohorts at 12 months, respectively. Moreover, increases in areal BMD were consistent across all OI subtypes (I, III or IV) represented in the study and improved with duration of treatment. Statistically significant changes in areal BMD were also observed by DXA at the femoral neck and total hip with mean increases of 3.1% (p=0.022) and 2.2% (P=0.011), respectively, at 12 months in the high dose cohort. Although the ASTEROID study was not powered to show a difference in fracture rates, a trend of reduction in fractures was observed in the high dose cohort. Setrusumab was safe and well-tolerated in the study. There were no cardiac-related safety concerns observed in the study. “These topline 12-month results from the ASTEROID study demonstrate a clear, dose-dependent, statistically significant bone building effect of setrusumab at multiple anatomical sites in adult OI patients irrespective of OI subtype,” said Dr. Denise Scots-Knight, Chief Executive Officer of Mereo. “The DXA data clearly differentiate setrusumab from other therapeutic agents in OI types I, III and IV, such as teriparatide, where a 4.7% increase was observed at the lumbar spine at 12 months and where the effect was significantly lower in types III & IV versus type I OI patients2. Further, the DXA data also show a consistent improvement at 12 months in areal BMD at the lumbar spine compared to the open-label data set from the study that we first reported in May 2019 where a 3.5% change from baseline was observed seen at 6 months in the highest dose cohort.” Dr. Scots-Knight continued, “The trend of decrease in fractures observed in the high dose cohort is also particularly encouraging. Based on these data, we are excited to move forward with the preparations for our pivotal pediatric study in children with OI as originally planned, which will be based on a primary endpoint of fracture rate over a 12-month period. We believe setrusumab has the potential to become the first approved pharmacologic treatment for the OI patient community and would like to thank the investigators and patients for participating in the ASTEROID study, the largest ever completed interventional trial in adult OI." “The technique of HR-pQCT is a relatively new and cutting-edge technology in bone research. We believe the HR-pQCT data from the ASTEROID study indicate a significant improvement in total vBMD that is driven by cortical changes, which differentiates setrusumab from existing bone-building agents,” said Dr. Alastair MacKinnon, Chief Medical Officer of Mereo. “It is important to emphasize that it is not possible to build bone that does not already exist, which may be the case with some patients’ trabecular bone at the wrist in this study given the variable HR-pQCT measurements of Tr vBMD. The total vBMD data together with the statistically significant and dose dependent improvement in areal BMD as measured by DXA, a well-established bone measurement technique, support the further development of setrusumab in pediatric patients, where the unmet medical need is most apparent.” “Taken in totality, the results from the ASTEROID study underscore the ability of setrusumab to function as a strong bone-building agent and potentially serve as a new therapeutic option for patients living with OI,” said Jay R. Shapiro, MD, F.A.C.E, F.A.C.P, Former Director of the Bone and Osteogenesis Imperfecta Department at the Kennedy Krieger Institute. “The fracture rate reduction seen in the highest dose cohort with setrusumab is particularly encouraging and bodes well for future development in pediatric OI patients.” Phase 2b ASTEROID Study Design Patient Baseline Demographics Patients in the trial had not been treated with bisphosphonates in the previous 3 months or other anabolic or anti-resorptive medications in the previous 6 months. 10 patients discontinued treatment with setrusumab in the blinded portion of the study. Efficacy Endpoint Results The study achieved its important secondary endpoint of increase in areal BMD at the lumbar spine at 6 and 12 months over baseline using two-dimensional dual-energy X-ray absorptiometry (DXA) measurement, reaching statistical significance in the high and medium doses cohorts at both 6 and 12 months, with a clear dose-dependent response. The magnitude of areal BMD changes over baseline at the lumbar spine at 6 months in the blinded high-dose cohort was consistent with the previously reported 6-month data from the open-label arm of the study.
Statistically significant changes in areal BMD were also observed by DXA at the femoral neck and total hip with mean increases of 3.2% (p=0.022) and 2.3% (P=0.009), respectively, at 12 months in the high dose cohort. Although the ASTEROID study was not statistically powered to show a difference in fracture rates, a trend of reduction in fractures was observed in the high dose cohort. Fractures in the study included both X-ray confirmed as well as those confirmed by a local radiologist dependant on the nature of the fracture.
Topline Safety Results Next Steps 81 patients who have completed 12-months of treatment in ASTEROID study have opted to continue into a 12-month extension “off therapy” portion to examine the off effect of setrusumab. Patients who continue in the extension portion have the option to receive 12 months of treatment with the bisphosphonate zoledronic acid (given at months 6 and/or 12). Patients will receive both DXA and HR-pQCT scans at 6 and 12 months after entering the extension portion. In addition to evaluating setrusumab in adult OI patients, Mereo's Paediatric Investigation Plan (PIP) has been approved by the European Medicines Agency (EMA) and a study design has been agreed for a pivotal study in children with OI, based on a primary endpoint of fracture rate over a 12-month period. The pivotal study will be conducted in approximately 165 children aged 5 to <18 years old, with OI, initially in EU and Canada, with potential expansion into the U.S. following planned discussions with the U.S. Food and Drug Administration (FDA). Conference Call Information About Osteogenesis Imperfecta About Setrusumab Mereo has obtained orphan drug designation in OI for setrusumab in both the United States and the EU, in February 2017 setrusumab was accepted into the EMA’s adaptive pathways program in the EU and, in November 2017 it was accepted into the EMA’s Priority Medicines scheme (PRIME). About Mereo BioPharma Mereo’s broader pipeline consists of four additional clinical-stage product candidates; acumapimod for the treatment of acute exacerbations of chronic obstructive pulmonary disease (“AECOPD”), leflutrozole for the treatment of hypogonadotropic hypogonadism (“HH”) in obese men, navicixizumab for the treatment of platinum-resistant ovarian cancer, and etigilimab for patients with advanced or metastatic solid tumors. Forward-Looking Statements Factors that could cause actual results to differ materially from those in the forward-looking statements include risks relating to unanticipated costs, liabilities or delays; failure or delays in research and development programs; the safety and efficacy of the Company’s product candidates and the likelihood of clinical data to be positive and of such product candidates to be approved by the applicable regulatory authorities; unanticipated changes relating to competitive factors in the Company’s industry; risks relating to the Company’s capitalization, resources and ownership structure, including as a result of circumstances affecting the Company’s former principal shareholder; the availability of sufficient resources for company operations and to conduct or continue planned clinical development programs, including the Company’s ability to continue as a going concern; the outcome of any legal proceedings; risks related to the ability to correctly estimate operating expenses; risks related to the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations; risks related to the changes in market prices of the Company’s ordinary shares; the Company’s ability to hire and retain key personnel; changes in law or regulations affecting the Company; international, national or local economic, social or political conditions that could adversely affect the Company and its business; conditions in the credit markets; risks associated with assumptions the Company makes in connection with its critical accounting estimates and other judgments. All of the Company’s forward-looking statements involve risks and uncertainties (some of which are significant or beyond its control) and assumptions that could cause actual results to differ materially from the Company’s historical experience and its present expectations or projections. The foregoing factors and the other risks and uncertainties that affect the Company’s business, including those described in its Annual Report on Form 20-F, Reports on Form 6-K and other documents filed from time to time by the Company with the United States Securities and Exchange Commission (the “SEC”) and those described in other documents the Company may publish from time to time should be carefully considered. The Company wishes to caution you not to place undue reliance on any forward-looking statements, which speak only as of the date hereof. The Company undertakes no obligation to publicly update or revise any of our forward-looking statements after the date they are made, whether as a result of new information, future events or otherwise, except to the extent required by law. 1Kocijan et al Osteoporos Int. Oct 2015; 2431-40
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