Safety and Efficacy of Apitegromab in Patients With Spinal Muscular Atrophy Types 2 and 3: The Phase 2 TOPAZ Study.

Background And Objectives: Currently approved therapies for spinal muscular atrophy (SMA) reverse the degenerative course, leading to better functional outcome, but they do not address the impairment arising from preexisting neurodegeneration. Apitegromab, an investigational, fully human monoclonal antibody, inhibits activation of myostatin (a negative regulator of skeletal muscle growth), thereby preserving muscle mass. The phase 2 TOPAZ trial assessed the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA.

A Randomized Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Novel Myostatin Inhibitor Apitegromab (SRK-015): A Potential Treatment for Spinal Muscular Atrophy.

Introduction: Apitegromab (SRK-015) is an anti-promyostatin monoclonal antibody under development to improve motor function in patients with spinal muscular atrophy, a rare neuromuscular disease. This phase 1 double-blind, placebo-controlled study assessed safety, pharmacokinetic parameters, pharmacodynamics (serum latent myostatin), and immunogenicity of single and multiple ascending doses of apitegromab in healthy adult subjects.

Methods: Subjects were administered single intravenous ascending doses of apitegromab of 1, 3, 10, 20, 30 mg/kg or placebo, and multiple intravenous ascending doses of apitegromab of 10, 20, 30 mg/kg or placebo.

Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis.

Background: Hereditary angioedema with C1 inhibitor deficiency is characterized by recurrent, unpredictable swelling episodes caused by uncontrolled plasma kallikrein generation and excessive bradykinin release resulting from cleavage of high-molecular-weight kininogen. Lanadelumab (DX-2930) is a new kallikrein inhibitor with the potential for prophylactic treatment of hereditary angioedema with C1 inhibitor deficiency.

Methods: We conducted a phase 1b, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial.

Ecallantide for the acute treatment of angiotensin-converting enzyme inhibitor-induced angioedema: a multicenter, randomized, controlled trial.

Study Objective: We compare the safety and efficacy of ecallantide with placebo in subjects undergoing assessment for acute angiotensin-converting enzyme inhibitor-induced angioedema (ACEIA) in an emergency department (ED).

Methods: This was a multicenter, phase 2, double-blind study with subjects randomized to receive a single subcutaneous dose of ecallantide (10, 30, or 60 mg) or placebo plus physician-directed conventional therapy. The primary endpoint was defined as meeting predetermined discharge eligibility criteria within 6 hours of study drug administration.

A phase 1 study investigating DX-2930 in healthy subjects.

Background: DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein under investigation for long-term prophylaxis of hereditary angioedema.

Objective: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of DX-2930 in healthy subjects.

Methods: A single-center, double-blinded study was performed in 32 healthy subjects randomized 3:1 to receive a single subcutaneous administration of DX-2930 or placebo within 1 of 4 sequential, ascending dose cohorts (n = 8 each): 0.

Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: open-label continuation study.

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of potentially life-threatening edema. The plasma kallikrein inhibitor ecallantide is approved for treatment of acute HAE attacks. This study evaluates the efficacy and safety of ecallantide for treatment of multiple HAE episodes in the DX-88/19 (continuation) study.