While clinical trials can be extremely helpful in the development of new treatments, not all trials go as planned. Recently, biotechnology company Regeneron Pharmaceuticals (“Regeneron”) discovered this firsthand. As the company announced in a press release, severe adverse reactions occurred in their Phase 1 LUMINA-1 trial. The trial is designed to evaluate garetosmab (REGN2477) for patients with fibrodysplasia ossificans progressiva (FOP). However, due to the severe and sometimes fatal reactions, Regeneron has suspended dosing in the trial.

LUMINA-1 Trial

44 patients (aged 18-60) enrolled in the LUMINA-1 trial. During the initial 28-week treatment period, in which patients received either garetosmab or a placebo, the investigational treatment showed promise. In fact, garetosmab reduced ossified lesions by 25% and FOP flares by 50%. However, the situation changed during the open-label extension period, during which time all 44 patients received garetosmab. Now, the trial is paused while Regeneron and other regulatory committees determine what role garetosmab played in the fatalities.

Outside of Regeneron, pharmaceutical company Ipsen is also searching for potential treatments for patients with FOP. In the Phase 3 MOVE trial, Ipsen analyzed palovarotene as a potential therapeutic option. 107 patients enrolled. During the trial, some patients received 5mg palovarotene daily, while others received 20mg daily for 4 weeks, followed by 10mg for 8 weeks. On one hand, the drug seemed relatively effective, reducing heterotopic ossification (HO) by 62%. At the same time, 67.7% of patients experienced moderate-to-severe adverse reactions.

Fibrodysplasia Ossificans Progressiva (FOP)

Approximately 1.3 million people across the globe have fibrodysplasia ossificans progressive (FOP). This rare disorder is caused by ACVR1 gene mutations. It is inherited in an autosomal dominant pattern, meaning it only requires one gene mutation. Normally, ACVR1 contributes to bone growth and development. However, this gene mutation causes muscle, ligaments, and tendons to become ossified. Basically, this means that these tissues become hardened and calcified, turning into bone outside of the skeletal structure.

Typically, symptoms and characteristics begin to appear in early childhood. As the disorder progresses, patients experience severely restricted movement. Symptoms or ossification may worsen after physical trauma or illnesses. Generally, ossification begins around the neck and shoulders. However, it later proceeds to the limbs. Symptoms and characteristics include:

• Loss of mobility
• Malformed big toes and thumbs
• Muscle inflammation
• Hair loss
• Difficulty speaking or eating
• Shortness of breath / difficulty breathing

Learn more about FOP.