Regeneron Pharmaceuticals said that the US FDA has approved the use of Pasatru in adults with fibrodysplasia ossificans progressive (FOP), a rare & debilitating bone-forming disorder that progressively turns soft connective tissue into bone.
Pasatru (garetosmab-grts) reduces the formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP).
The approval gives people living with FOP a new treatment option for a disease that can steadily destroy mobility and make basic activities such as speaking, eating, walking and breathing increasingly difficult.
Pasatru can be administered in a range of care settings, including home infusion where appropriate. The recommended starting dose is 10 mg/kg, delivered intravenously over 60 minutes once every four weeks. For patients who do not tolerate that dose, treatment may be reduced to 3 mg/kg once monthly.
FOP affects muscles, tendons, ligaments and other connective tissues, which become progressively infiltrated by abnormal bone. HO in the jaw, spine, hips and rib cage can severely restrict movement and function. About 900 people worldwide are diagnosed with FOP, and most patients become wheelchair-bound by age 30. The median age of survival is 56.
“For people living with FOP, every irregular new bone formation is a step toward disability and potential loss of mobility,” said Kathryn Dahir, Professor in the Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism at Vanderbilt University, and a primary investigator for the OPTIMA trial. “With the ability to reduce the number of new bone lesions and flare-ups, we now have a new treatment that can positively affect patients.”
“This approval is monumental for our community, providing a vital new therapy that can have a significant impact on the life of someone with FOP."
The approval was supported by results from the Phase 3 OPTIMA trial, which evaluated Pasatru in adults with FOP. After 56 weeks, both the 10 mg/kg and 3 mg/kg doses significantly reduced the number of new HO lesions compared with placebo.
Patients receiving 10 mg/kg experienced 2 new lesions versus 19 among those receiving placebo, a 90% reduction. The 3 mg/kg group recorded 1 new lesion versus 19 with placebo, representing a 94% reduction.
Clinician-assessed flare-ups also fell sharply with the 10 mg/kg dose. There were 9 flare-ups in that group, compared with 66 among patients receiving placebo, an 88% reduction. The 3 mg/kg group recorded 53 flare-ups, a 15% reduction versus placebo.
However, changes in patient-reported flare-ups through week 56 were not significantly different between the Pasatru and placebo groups.
Among the 63 trial participants, serious treatment-emergent adverse events occurred in two patients receiving 10 mg/kg Pasatru, one receiving 3 mg/kg and two receiving placebo.
The most common adverse reactions in at least 10% of adults treated with Pasatru included abscess, acne, increased hair growth, loss of eyebrows, oral ulcers, nosebleeds, folliculitis, nail infection and rash.
Pasatru is a fully human monoclonal antibody derived using Regeneron's VelocImmune technology. The drug blocks Activin A, a protein Regeneron scientists identified as playing a critical role in the development of HO lesions in people with FOP.
“The approval of Pasatru is the culmination of decades of pioneering research that Regeneron has pursued alongside the FOP community, rooted in our discovery of the role that Activin A plays in driving this disease,” said George D. Yancopoulos, Board co-Chair, President and Chief Scientific Officer at Regeneron.
“People living with FOP have needed a new treatment option for this devastating condition far too long, much like many others living with a rare disease. This unprecedented milestone embodies our broader mission to continue delivering new options for those who have long faced limited treatment options and our relentless commitment to bringing scientific breakthroughs to families, no matter the prevalence of the condition they manage.”
Regeneron said its myRARE program will provide resources for patients and healthcare providers, including product information, insurance benefit verification and information on potential financial assistance.
