Rare Daily Staff

A drug Roche had unsuccessfully sought to develop as a treatment for chronic obstructive pulmonary disease has shown promise in preclinical testing as a potential treatment for a rare genetic bone disease.

Researchers at Sanford Burnham Prebys Medical Discovery Institute led a team that showed the experimental drug palovarotene suppressed the formation of bony tumors in models of multiple hereditary exostoses or MHE, a disorder that causes multiple benign tumors covered with cartilage grow at active areas of bone growth.

The research, published in the Journal of Bone and Mineral Research, represents a step toward having an effective to treat MHE, which affects about 1 in 50,000 people worldwide. Individuals with these mutations develop painful, debilitating tumors, often repeatedly during their childhood and adolescence. Surgery and pain management are currently the only treatment options for MHE patients.

“Our study shows that palovarotene is a remarkably potent inhibitor of osteochondromas,” said Yu Yamaguchi, professor at Stanford Burnham Prebys. “In our mouse model of MHE, we were able to reduce bone tumors by more than 90 percent, which is a significant improvement over the previous drugs we have tested in the same mouse model.”

Because of Roche’s past development efforts on palovarotene, it has been tested for toxicity and side effects in humans and has been shown to be well tolerated. Yamaguchi said that mean that the timeline for getting the drug to the clinic for MHE may be shortened.

Clementia Pharmaceuticals licensed palovarotene from Roche. It is planning to initiate a phase 2/3 clinical trial in 2018 for patients with MHE. Clementia is also pursuing a late-stage study of palovarotene as a treatment for fibrodysplasia ossificans progressive, an ultra-rare and severely disabling condition characterized by the abnormal growth of bone in muscles, tendons, and soft tissue.

“This is first time we are seeing a clear path toward a therapy that will improve the lives of MHE patients and their families,” says Sarah Ziegler, vice-president of the MHE Research Foundation. “The long awaited first clinical trial for a drug to treat MHE is now a reality. This breakthrough comes after years of working with medical professionals and scientists like Dr. Yamaguchi to achieve something we have all been desperately striving for, for many years.”

November 20, 2017