Announcement • 1h
Regeneron Pharmaceuticals Announces FDA Approval for Pasatru to Reduce Formation of New Heterotopic Ossification Lesions and Clinician-Assessed Flare-Ups in Adults with Fibrodysplasia Ossificans Progressiva
Regeneron Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) has granted approval for Pasatru™ (garetosmab-grts) to reduce formation of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults with fibrodysplasia ossificans progressiva (FOP). Pasatru can be administered across a range of care settings, including home infusion where appropriate. The recommended starting dosage is based on weight at 10 mg/kg and is given intravenously over 60 minutes once monthly (every four weeks) but may be decreased to a 3 mg/kg infusion over 60 minutes once monthly if not tolerated. Pasatru is a VelocImmune®-derived, fully human monoclonal antibody that blocks Activin A, a protein that Regeneron scientists discovered to be critical in the development of HO lesions in people with FOP. Pasatru was granted approval based on efficacy and safety data from the positive Phase 3 OPTIMA trial evaluating Pasatru in adults with FOP. At 56 weeks, both doses of Pasatru, 10 mg/kg (n=23) and 3 mg/kg (n=19), met the primary endpoint and were highly efficacious in reducing the total number of new HO lesions as compared to placebo (n=21), demonstrating a 90% (2 lesions vs. 19 lesions) and 94% (1 lesion vs. 19 lesions) reduction, respectively, as assessed by computed tomography (CT) scan. The number of clinician-assessed flare-ups during this time, a key secondary endpoint, were 9 for Pasatru 10 mg/kg (88% reduction compared to placebo), 53 for Pasatru 3 mg/kg (15% reduction compared to placebo), and 66 for placebo. Changes in the proportion of patients with patient-reported flare-ups through week 56 were not significantly different between placebo and Pasatru treatment groups. At 56 weeks, among all 63 people who participated in the trial, serious treatment-emergent adverse events occurred in 2 patients treated with 10 mg/kg Pasatru, 1 patient treated with 3 mg/kg Pasatru, and 2 patients treated with placebo. The most common adverse reactions occurring in =10% of adults with FOP treated with Pasatru 10 mg/kg or 3 mg/kg were abscess, acne, increased hair growth, madarosis (loss of eyebrows), oral ulcers, epistaxis (nosebleeds), folliculitis, paronychia (nail infection), and rash. Pasatru was granted approval based on efficacy and safety data from the positive Phase 3 OPTIMA trial evaluating Pasatru in adults with FOP. OPTIMA is a Phase 3, multi-center, multinational trial to assess the efficacy of Pasatru on the reduction of heterotopic bone formation and flares, as well as its safety, tolerability, and pharmacokinetics, in patients with active FOP. The trial enrolled 63 participants aged 18 years and older who have any FOP-causing variant of type I Activin A receptor (ACVR1), exhibited FOP disease activity or progression of HO lesions, and had a cumulative analogue joint involvement scale (CAJIS) score at screening of =19. CAJIS is a scoring tool used by clinicians to assess the degree of joint involvement, with higher scores representing a greater degree of disease severity (scale: 0 to 30). Eligible participants were randomized to receive intravenously administered Pasatru 10 mg/kg, Pasatru 3 mg/kg, or placebo once every four weeks for 56 weeks. Following this, participants could elect to then continue their originally assigned treatment in a double-blind extension phase for at least 84 weeks or discontinue treatment and enter an observation-only arm. During the treatment period, efficacy was evaluated through whole body CT scans for HO lesions, physician and patient assessment of flare-ups, utilization of CAJIS to rate joint functionality, and observances of change in disease severity. Safety assessment includes reports of adverse events, measurement of vital signs, physical examination, and coagulation testing. A Phase 3 trial of Pasatru in adolescents and children with FOP, OPTIMA 2, is planned to begin later this year. Pasatru is a VelocImmune-derived, fully human monoclonal antibody that binds and neutralizes Activin A, which is involved in the development of heterotopic bone in people with FOP. PASATRU can cause serious side effects, including harm to your unborn baby including serious birth defects if taken during pregnancy. Females who are pregnant must not take PASATRU. Females who can become pregnant: Your healthcare provider will ask you to take a pregnancy test to verify that you are not pregnant before starting treatment with PASATRU. Use effective birth control (contraception) during treatment with PASATRU and for 6 months after the last dose of PASATRU. If you become pregnant or think you may be pregnant during treatment with PASATRU, stop taking PASATRU immediately and call your healthcare provider right away. Infections of the skin and tissue under the skin requiring treatment or hospitalization, such as infected lumps (abscesses) and bacterial skin infections (cellulitis), may happen while you are taking PASATRU. Call your healthcare provider right away if you have signs or symptoms of skin infection, such as pain or tenderness, redness, fever, skin feels warm to the touch, feeling generally unwell, swelling. Nosebleeds (epistaxis) including serious nosebleeds that require medical care, can happen while taking PASATRU. Tell your healthcare provider right away if you have a nosebleed that is severe or heavy, does not stop with basic first-aid measures, such as pinching your nose with continuous firm pressure, lasts more than 20 minutes. Do not receive PASATRU if you are pregnant. Before you receive PASATRU, tell your healthcare provider about all your medical conditions, including if you are breastfeeding. It is not known whether PASATRU passes into your breastmilk. Breastfeeding is not recommended during treatment with PASATRU and for 6 months after the last dose of PASATRU. Talk to your healthcare provider about the best way to feed your baby during this time. Are concerned about male fertility. PASATRU may affect your ability to father a child. Talk to your healthcare provider if this is concern for you. Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. The most common side effects of PASATRU include infected lumps (abscess), hair loss of eyebrows or lashes (madarosis), acne, increased hair growth, mouth sores (oral ulcers), nosebleeds (epistaxis). These are not all of the possible side effects of PASATRU. PASATRU™ (garetosmab-grts) is a prescription medicine used to reduce the formation of new abnormal bone growth outside of the skeleton (heterotopic ossification) and flare-ups in adults with fibrodysplasia ossificans progressiva (FOP). It is not known if PASATRU is safe and effective in children.