Cremer, Malika, Rooks, Daniel, Fretault, Nathalie, Schubert-Tennigkeit, Agnes Annette and Papanicolaou, Dimitris (2021) Bimagrumab to Improve Recovery after Hip Fracture in the Elderly: A Randomised, Double-Blind, Placebo-Controlled Phase 2a/b Study. The Lancet Healthy Longevity, 2 (5). E263-E274.

Abstract

Background: Elderly patients undergoing surgery for hip fracture repair frequently experience loss of muscle mass and strength due to immobility, which may delay functional recovery. This study investigated whether bimagrumab, a human monoclonal antibody targeting activin type II receptors (ActRII), can improve postsurgical recovery.

Methods: This was a randomised, double-blind, parallel-group, placebo-controlled Phase 2a/2b trial conducted at 50 centres in 18 countries. Patients aged ≥60 years who recently (past 6 weeks) underwent surgery for hip fracture were enrolled to receive intravenous treatment with either placebo or one of three doses of bimagrumab (70 mg, 210 mg, and 700 mg) every 4 weeks for 24 weeks. The primary endpoint was the change from baseline in total lean body mass (LBM) measured by dual-energy X-ray absorptiometry (DEXA) at Week 24. Key secondary endpoints included the respective changes in habitual gait speed (m/s) and the Short Physical Performance Battery (SPPB). Safety and tolerability were assessed by recording adverse events (AEs), physical examination, vital signs, laboratory assessments, and electrocardiography. (ClinicalTrials.gov, NCT02152761).

Findings: Of the 250 treated patients, 207 (83%) completed the treatment period. The absolute increase in LBM from baseline was dose dependent, with mean±standard deviation gains of 1·9±1·7 kg in the bimagrumab 210 mg group and 2·8±2·2 kg in the 700 mg group, compared with 0·3±2·0 kg in the placebo group (both p<0·001). Changes in the key secondary endpoints were similar across treatment groups suggesting no enhancement of physical recovery with bimagrumab over placebo. Bimagrumab was safe and well tolerated; the most frequently reported AEs were falls, muscle spasms, and arthralgia.

Interpretation: Twenty-four weeks of treatment with bimagrumab led to dose-dependent and clinically meaningful increases in LBM in elderly hip fracture patients. However, no functional benefit was seen in terms of the recovery of mobility or physical performance compared to placebo.

Item Type:	Article
Keywords:	bimagrumab, hip fracture, D2201
Date Deposited:	27 Jul 2021 00:45
Last Modified:	27 Jul 2021 00:45
URI:	https://oak.novartis.com/id/eprint/43798