Ultragenyx and Mereo BioPharma Face Setback in Osteogenesis Imperfecta Trial

Ultragenyx Pharmaceutical and Mereo BioPharma experienced a significant blow to their stock prices following the announcement that their Phase II/III study for an osteogenesis imperfecta (OI) treatment will proceed to final analysis. The news, which implies that the trial did not meet early efficacy thresholds, sent shares tumbling and raised questions about the future of the investigational therapy UX143.

Trial Disappointment and Market Reaction

The partners revealed that the Orbit study, evaluating UX143 (setrusumab) for OI, will continue to its final analysis rather than concluding early due to overwhelming efficacy. This development suggests that the trial failed to achieve the minimal p-value threshold of p<0.01 at the second interim analysis, which would have allowed for early termination of the study.

In response to the announcement, Ultragenyx's stock plummeted by 21%, while Mereo BioPharma saw an even steeper decline of 30% in premarket trading. The lack of specific efficacy data, withheld to maintain study integrity, left investors and analysts speculating about the extent of the shortfall.

Understanding Osteogenesis Imperfecta and UX143

Osteogenesis imperfecta, affecting approximately 1 in 15,000 to 20,000 births, is a rare genetic disorder characterized by extremely fragile bones. The condition is primarily caused by mutations in the COL1A1 or COL1A2 genes, which are responsible for producing collagen, a crucial component of bone structure.

UX143, also known as setrusumab, is a monoclonal antibody designed to target and inhibit sclerostin, a protein that suppresses bone formation. By blocking sclerostin, the drug aims to enhance bone formation, normalize bone mass, and strengthen bones against fractures. Previous Phase IIb data from November 2019 showed promising results, with various doses of UX143 improving total volumetric bone mineral density by 4.1% to 4.5% over a 12-month treatment period.

Looking Ahead: Remaining Clinical Trials and Expert Opinions

Despite the setback, some analysts remain cautiously optimistic about the trial's final outcome. William Blair analysts suggested that the market reaction may be "severely overdone," citing a lower bar for statistical significance at the final analysis and the benefit of longer patient follow-up.

Ultragenyx and Mereo are also conducting the pivotal Phase III Cosmic trial, an open-label, randomized, and active-controlled study testing UX143 in 69 patients aged 2 through 6 years. Results from both the Orbit and Cosmic trials are anticipated "around the end of this year," according to Ultragenyx CEO Emil Kakkis.

As the pharmaceutical industry awaits the final analysis of the Orbit study and the results of the Cosmic trial, the future of UX143 and its potential impact on osteogenesis imperfecta treatment remain uncertain. The coming months will be crucial in determining whether this setback is a minor hurdle or a significant obstacle in the development of a novel therapy for this rare genetic disorder.