Pediatric data show substantial induction of bone production in 1 week and a large increase in bone formation within 3 months of initiating monthly setrusumab treatment
Phase 3 sites beginning to screen patients
Conference call to discuss data planned for 5 p.m. Eastern Time
NOVATO, Calif. and LONDON, June 05, 2023 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) and Mereo BioPharma Group plc (NASDAQ: MREO) today announced data from the dose-selection Phase 2 portion of the Phase 2/3 Orbit study showing that setrusumab rapidly induced bone production in OI-affected patients. Across all patients evaluated setrusumab demonstrated statistically significant increases in levels of serum P1NP, a sensitive marker of bone formation, and a substantial and significant improvement in bone mineral density (BMD) by 3 months.
“The rate of increasing bone mineralization we're observing on DXA scans is striking, unlike anything I have typically seen with bisphosphonate therapy. This increase in bone mass underscores the potential to make denser and stronger bone,” said Gary Gottesman, M.D., Professor of Pediatrics and Medicine, Washington University School of Medicine.
As of the data cut off, serum P1NP levels through at least 1 month of treatment were available from all 24 patients enrolled in Orbit and demonstrated that treatment with setrusumab significantly increased serum P1NP in both dosing cohorts, peaking at one to two weeks and again, as expected, after the 2-month dosing timepoint. In the 20 mg/kg cohort, there was a mean serum P1NP increase of 57% from baseline over the first month. Because of the higher baseline P1NP level in younger patients, this represents an approximate 8-fold greater increase in serum P1NP over 1 month in pediatric and adolescent patients when compared to adult OI patients. The absolute effect of setrusumab on increasing serum P1NP over the 1-month period with the 20 mg/kg dose, was approximately 80% of the effect achieved with the 40 mg/kg dose, demonstrating a dose response. Patients on placebo at the 1-month timepoint (n=4) showed no significant change in mean serum P1NP from baseline.
The large increase in BMD observed in the Orbit patient population over the first 3 months was consistent with the rapid increase in serum P1NP levels and was similar to results that took 1 year to achieve in the ASTEROID study in adult OI patients. Lumbar spine BMD data were available in 17 of 24 Orbit patients at the 3-month timepoint. Treatment with setrusumab for 3 months resulted in an increase in lumbar spine BMD from baseline of 9.4% at 20 mg/kg (n=10), which represents a substantial mean change in Z-score of +0.65. Treatment with 40 mg/kg (n=7) resulted in a 9.8% BMD increase. Patients on placebo at the 3-month timepoint (n=2) showed no significant change in BMD or change in lumbar spine Z-score.
“The dramatic lumbar spine BMD improvements in children at 3 months show that growing bones are more dynamic, and we anticipate the potential for a greater effect on bone formation and strength in younger patients with maturing bones,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “Based on the reports from study investigators, we’re encouraged by the impact setrusumab appears to be having on bone health so far.”
As of the data cut-off, there have been no treatment-related serious adverse events observed in the study. Reported adverse events have been generally consistent with those observed in the ASTEROID study and include infusion associated events, headache and sinusitis. There have been no reported hypersensitivity reactions related to setrusumab. There were no safety-related differences observed between dosing groups or age groups.
The totality of data demonstrated meaningful response in serum P1NP and BMD across both cohorts, with the majority of the effect observed at 20 mg/kg, which is the dose planned across the setrusumab Phase 3 program. Screening has begun for the Phase 3 portion of the study, which is designed to enroll approximately 195 patients at more than 40 sites across 12 countries.
Investor Conference Call and Webcast InformationUltragenyx will host an investor conference call today, Monday, June 5, at 2 p.m. PT / 5 p.m. ET to discuss the results. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations. To participate in the live call, please register by clicking on the following link (registration link), and you will be provided with dial in details. The replay of the call will be available for one year.
The Setrusumab Phase 3 ProgramUltragenyx and Mereo are developing setrusumab in pediatric and young adult patients across OI sub-types I, III and IV with two late-stage trials: the pivotal Phase 2/3 Orbit study and Phase 3 Cosmic study.
The global, seamless Phase 2/3 Orbit study is evaluating the effect of setrusumab versus placebo on fracture rate in patients aged 5 to