With phase II trials ongoing in chronic obstructive pulmonary disease (COPD) and low testosterone in obese men, Mereo Biopharma Group plc is launching a potentially pivotal phase IIb experiment called Asteroid testing BPS-804 in adults with the rare genetic disorder osteogenesis imperfecta (OI), also known as brittle bone disease.

CEO Denise Scots-Knight told BioWorld Today that the effort with BPS-804 has been admitted into the EMA’s Adaptive Pathways Program whereby “you have an interactive dialogue with the EMA over what’s needed to get conditional approval and then, post-conditional approval, collect real-world data,” she said. And what about U.S. regulators? “The FDA said, ‘Come back with your data.’”

A pediatric study in OI will begin later this year. “One of the reasons for starting that much earlier than we probably would have otherwise, is that when we go back to the FDA, we want to [have] data in adults and in children,” Scots-Knight said.

OI treatment today is mostly surgical, focused on reducing pain and relieving complications. Granted orphan drug status by the FDA and EMA, BPS-804 is a fully humanized monoclonal antibody that inhibits sclerostin, a protein that prevents the activity of bone-forming cells. London-based Mereo acquired the compound from Novartis AG, of Basel, Switzerland, which developed it by way of a deal with Morphosys AG, of Planegg, Germany. (See BioWorld Today, Dec. 4, 2007.)

Novartis was investigating BPS-804 in osteoporosis, and “OI was used as a proof of mechanism of action in terms of bone building,” Scots-Knight said, adding that the compound had reached the phase II stage. BPS-804 is meant to increase bone formation and cut down resorption, thereby strengthening the bone and reducing fractures. So far, studies in 83 patients have shown that BPS-804 is safe and well-tolerated. BPS-804 has turned up a statistically significant improvement in bone mineral density and on biomarkers as well, Mereo said, and its program is expected to enroll up to 120 adult patients in a randomized, double-blind, placebo-controlled, multicenter experiment in the U.S. and Europe. The primary endpoint is change in trabecular volumetric bone mineral density measured by high resolution peripheral quantitative CT (HRpQCT) and change in bone strength on finite element analysis. Additional endpoints include further measures of bone parameters on HRpQCT, bone turnover markers and quality of life scores.

“With the adult program, we’re thinking the enrollment is going to take anything between six to nine months,” Scots-Knight said. “We’ll have to see how it goes, because we are in somewhat uncharted territory, but that’s what we’re thinking at the moment.”

The primary endpoint will be checked at six months, and patients will be followed for 12 months to evaluate maintenance therapy. “The way that we’ve designed the study, after six months all the patients get to go onto an active dose,” she said. “The placebo arm is just for the six months.”

Mereo is working with patient advocacy groups. “In the U.S., you have the OI Foundation, and in the EU, there are a couple of smaller charities in a similar vein,” she said. “We’re very engaged with those organizations as we work through the study. They understand what we’re doing and why we’re doing it.”

If and when the time comes, Mereo will commercialize BPS-804 alone. “Probably you need to hit around 100 sites, and that’s counting the EU and U.S., so we think that’s eminently doable by a small company,” Scots-Knight said. The compound’s sclerostin-targeting mechanism of action will be familiar to followers of progress with romosozumab (often shorthanded as “romo”), subject of a partnership between Thousand Oaks, Calif.-based Amgen Inc. and UCB SA, of Brussels, Belgium.

Last September, the FDA accepted the BLA for romo to treat osteoporosis in postmenopausal women at increased risk of fracture. The PDUFA date is July 19. That antibody was developed by Celltech Group plc, of Slough, U.K., which signed a deal with Amgen in 2002; UCB acquired Celltech in 2004 for $2.7 billion. About a year ago, the companies reported that romo met its primary endpoint in a pivotal phase III study, called Bridge, providing men with osteoporosis with a statistically significant increase in bone mineral density at the lumbar spine vs. placebo at 12 months. (See BioWorld Today, May 19, 2004, and March 22, 2016.)

Scots-Knight said Mereo has “two other decent-sized phase IIs ongoing. The first one we’ve been enrolling for a while, and we’re getting close” with the P38 map kinase therapy for acute exacerbations of COPD. “We’re expecting the top-line data later this year” from the 270-patient trial, she said. Also in phase II and enrolling the same number of patients is an aromatase inhibitor for hypogonadism. The study is “well underway,” with its data due late this year as well.

“Our plan is to build a commercial company based around orphan diseases, and we’re in active dialogue with a couple of pharma companies at the moment around some additional orphan products to add to the portfolio,” she said. Regarding the COPD and hypogonadism candidates, “depending on the data, we’ll decide how far we want to take them before we partner them,” she said.

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