Romosozumab-AQQG

A new readout offers encouragement as Ultragenyx and Mereo BioPharma advance toward data from the phase 3 portion of the trial. Ultragenyx and Mereo BioPharma have broken off another piece of brittle bone data, linking their drug candidate to sustained reductions in fracture rates in a midphase clinical trial.  The results come from 24 patients with osteogenesis imperfecta who received the anti-sclerostin antibody setrusumab in the first part of the phase 2/3 Orbit study. Over the two years before the trial, the patients had a median annualized fracture rate of 0.72. In October, the partners reported the median annualized fracture rate fell to zero after the participants had received setrusumab for an average of nine months. Ultragenyx and Mereo’s latest cut of the data looks at outcomes after a mean treatment duration of 16 months. The headline result is a carbon copy of the earlier readout, with the partners again reporting a 67% reduction that kept the median annualized fracture rate down at zero. Pamidronate and zoledronic acid, currently prescribed brittle bone treatments, are associated with lower rates of fracture reduction.  The result is in line with the bar set by Mereo CEO Denise Scots-Knight, who told attendees at a Jefferies event last week that she expected the readout to be “at least comparable, if not better than” the earlier data drop. Shares in Mereo climbed more than 6% to $3.75 in premarket trading, and Ultragenyx’s stock traded up 4% to top $43. Ultragenyx and Mereo also shared updated bone mineral density (BMD) data. Scots-Knight flagged BMD as a result to watch at the Jefferies event, explaining that her team would be “looking at whether it's increasing in a linear manner or starting to plateau” to inform potential maintenance dosing regimens.  Lumbar spine BMD had increased 22% from baseline after 12 months of treatment without evidence of plateau. The result shows density continued to increase after the six-month analysis, when the partners reported a 14% rise, and suggests further gains are possible as Ultragenyx and Mereo continue to track the patients.  The readout offers encouragement as the partners advance toward data from the phase 3 portion of the trial. Ultragenyx wrapped up enrollment in the phase 3 part of the Orbit study, which recruited people aged 5 to 25 years, and in another phase 3 study in younger children in April. Speaking at a Goldman Sachs event Tuesday, Ultragenyx CEO Emil Kakkis said an interim analysis is due around the end of 2024. “I think we'll end early, but I don't know for sure,” Kakkis said. “Based on the size of the trial, and the fracture reduction we're seeing, we should. But it highly depends on how many fractures are happening. That part is hard to predict.”

Ultragenyx and Mereo BioPharma unveiled longer-term results for their investigational anti-sclerostin antibody setrusumab showing sustained reductions in fracture rates and improvements in bone mineral density (BMD) for patients with the rare, inherited brittle bone disease osteogenesis imperfecta (OI).Previously reported six-month data had shown a 67% reduction in annualised rate of radiologically confirmed fractures across all 24 patients in the Phase II portion of the pivotal ORBIT trial following at least six months of treatment with setrusumab.The latest results indicate this benefit was maintained in OI patients with at least 14 months of follow-up. Setrusumab also resulted in a mean 22% increase in lumbar spine BMD at 12 months compared to baseline levels across all age groups in the study, which includes patients from 5 to <26 years old. The companies said this effect translated to a substantial normalisation in Z-score of +1.25, progressing from the +0.85 increase seen at 6 months."The clinically meaningful continued improvement in BMD suggests that new and stronger bone is being created that has resulted in an important reduction in fractures across age groups and types of OI," noted Eric Crombez, chief medical officer at Ultragenyx.No new safety signals emerged with the longer-term setrusumab exposure. There were no treatment-related serious adverse events (AEs) either, and AEs were "generally consistent" with those seen previously in the Phase IIb ASTEROID study of setrusumab in 112 adults with OI, the companies said. Detailed 14-month data will be presented at a future scientific meeting.Late-stage testing under wayThe Phase III portion of the ORBIT study has enrolled an additional 158 patients aged 5 to 25 years, randomised to receive setrusumab or placebo, with a primary endpoint of annualised clinical fracture rate. Primary completion is set for early next year. Meanwhile, in the open-label Phase III COSMIC study, 69 children ages 2 through 7 years were randomised to setrusumab or intravenous bisphosphonate therapy, assessing reduction in total fracture rate.Enthusiasm appears to be building for setrusumab. In a recent note, Goldman Sachs analyst Salveen Richter expressed confidence in the drug based on positive feedback from key opinion leaders regarding the Phase II data. She noted "the potential for setrusumab to improve bone formation and strength in addition to reducing fractures via its sclerostin inhibition mechanism, a key differentiator vs. standard-of-care bisphosphonates."Ultragenyx entered a collaboration and licence agreement with Mereo in 2020 to bolster its existing bone franchise, which includes Crysvita (burosumab-twza) for X-linked hypophosphatemia and tumour-induced osteomalacia. Mereo received $50 million upfront as part of the deal and is eligible for milestones up to $254 million.