Regeneron Pharmaceuticals shares safety and efficacy information from the clinical trial of garetosmab, a fully-human monoclonal antibody blocking activin A
On January 12, 2023, Regeneron Pharmaceuticals published LUMINA-1 Phase II Trial Results in medRxiv. medRxiv publishes preprints that have not been certified by peer review. You can see a list of authors on this publication below.
Maja Di Rocco, Eduardo Forleo-Neto, Robert Pignolo, Richard Keen, Philippe Orcel, Thomas Funck-Brentano, Christian Roux, Sami Kolta, Annalisa Madeo, Judith S Bubbear, Jacek Tabarkiewicz, Małgorzata Szczepanek, Javier Bachiller-Corral, Angela M Cheung, Kathryn M Dahir, Esmée Botman, Pieter G Raijmakers, Mona Al Mukaddam, Lianne Tile, Cynthia Portal-Celhay, Neena Sarkar, Peijie Hou, Bret Musser, Anita Boyapati, Kusha Mohammadi, Scott Mellis, Aris N Economides, Dinko Gonzalez Trotter, Gary Herman, Sarah J O'Meara, Richard DelGizzi, David M. Weinreich, George D Yancopolous, E. Marelise W Eekhoff, Frederick S Kaplan
What’s Included in the medRxiv Publication
The medRxiv publication includes a 386-word Abstract, a 52-page publication and 67 pages of Supplementary Material. There is a lot of information in the Supplementary Material, so we have created a table of contents below.
As we see the first published results of the garetosmab LUMINA-1 Phase II Trial, which also includes case summaries of the individuals with FOP who passed away, we are grateful for the 44 families that participated in this important clinical trial. We also appreciate the work of the trial investigators and their commitment to FOP families. We are also grateful to Regeneron Pharmaceuticals for their commitment to the FOP community and the development of garetosmab. We await publication in a peer-reviewed journal.
Questions about this publication? Contact us at [email protected]
Phase III Clinical Trial
If you would like more information about the OPTIMA Phase III Clinical Trial for garetosmab, visit ifopa.org/optima.
Some key terms you'll find in the publication.
Period 1 – Adult patients with FOP were randomized to garetosmab or placebo for 28 weeks
Period 2 – Open-label treatment period where all adult patients received garetosmab for 28 weeks
Open-label Extension – Patients were allowed to stay on garetosmab in an open-label extension following the end of Period 2
Adverse Event (AE) and Treatment Emergent Adverse Event (TEAE)
Source: European Patients’ Academy on Therapeutic Innovation
In medicines development terminology, an adverse event is any undesirable event that occurs after a participant officially consents to take part in a trial
(and could occur before treatment begins).
An adverse event may or may not be associated with the medicine under investigation, but must be documented because it happened during the trial period.
Treatment emergent adverse events are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.
A treatment emergent adverse event is an adverse event that occurs only once treatment has started.
HO-Total Lesion Activity (HO-TLA) – Heterotopic ossification total lesion activity (evaluated by 18F-sodium fluoride positron emission tomography ([18F-NaF PET])
HO Total Lesion Volume – Heterotopic ossification total lesion activity evaluated by computed tomography (CT) scan
Table of Contents for Supplementary Materials
Figure S1. Activin A activates signaling by FOP-mutant ACVR1 but inhibits signaling by wild type ACVR1 - Page 1
Figure S2. Schematic overview of the study design - Page 2
Figure S3. Trial profile - Page 3
Figure S4. Percent of patients with new lesions by quantitative imaging in Period_1 - Page 4
Figure S5. Effect of garetosmab on flare-up events - Page 5
Figure S6. Effect of garetosmab in Period_2 relative to Period_1 - Page 6
Figure S7. Coagulation and platelet functional assays at baseline and post treatment in LUMINA-1 patients - Page 7
Figure S8. Changes in BMP9 levels are minor and not associated with episodes of epistaxis - Page 9
Table S1. Overview of protocol and statistical methodology amendments - Page 13
Table S2. Key inclusion/exclusion criteria - Page 21
Table S3. List of Key Primary and Secondary Outcomes for Period_1, Period_2 and open label extension (Per Protocol) - Page 22
Table S4. Baseline demographics and disease characteristics - Page 27
Table S5. Summary of primary, and secondary endpoints for Period_1 and Period_2 - Page 30
Table S6. Key prespecified secondary, exploratory, and post-hoc analyses for Period 1 - Page 36
Table S7. TEAEs that occurred in ≥10% of the garetosmab 10 mg/kg Q4W group in the double-blind period of the study (Period_1) - Page 38
Table S8. Skin and soft tissue infection TEAEs - Page 41
Table S9. Serious adverse events that occurred in the double-blind period of the study (Period_1) - Page 43
Table S10. Bleeding TEAEs - Page 44
Table S11. TEAEs that occurred in ≥10% in Period_2 and the open-label extension period until end of study - Page 45
Table S12. Serious adverse events that occurred in the open-label period - Page 48
Table S13. Case summaries of patients who died - Page 50
Table S14. Exploratory analysis of percent change of total volume (cm3) of target lesions by CT at week 8 and week 28 versus baseline - Page 54
Study Sites and Investigators - Page 56
Supplementary section: Methods - Page 57
Supplementary section: Results - Page 65
Supplementary references - Page 67