Plain Language Summary
What is this summary about?
This is a plain language summary of a clinical research study called LUMINA-1. This study investigated a medicine called garetosmab in adults with fibrodysplasia ossificans progressiva, or FOP. FOP is a very rare disease that causes new bone to form in places where it does not usually develop (also known as heterotopic ossification). In FOP, when bone is formed in areas it is not supposed to, it results in mature heterotopic bone. The build-up of new bone makes it difficult for people with FOP to move, which means they often require the use of a wheelchair or other mobility aid. People with FOP who took part in the study were experiencing bone formation in areas where new bone should not form, flare-ups (episodes of localized swelling, pain, and/or warmth), and worsening joint movement.
What were the results?
People with FOP were given garetosmab or placebo every 4 weeks as a liquid infusion through a vein for 28 weeks. After 28 weeks, those who were receiving placebo were switched to garetosmab and treated for 28 weeks. This part was known as the open-label portion of the trial, which is when all people received garetosmab treatment. Treatment with garetosmab did not change the mature heterotopic bone in people with FOP, but it did stop new bone lesions from forming in areas where they should not. Treatment with garetosmab also reduced the number of flare-ups. During the trial, common side effects were nosebleeds, loss of eyebrows or eyelashes, and skin and soft tissue infections. Five people died during the open-label portion of the trial, when all were on garetosmab. Their deaths appeared consistent with the known causes of death and life expectancy of people with FOP who were of a similar age and severity of disease. There was no clear pattern that linked the deaths with how garetosmab works. However, a causal relationship between deaths and garetosmab could not be ruled out.
What do the results of the study mean?
The LUMINA-1 study showed that in people with FOP, garetosmab stopped new heterotopic bone from developing in areas that it should not and also reduced flare-ups. This shows that garetosmab may be a useful treatment for people with FOP. More testing is needed to better understand the benefits and risks of garetosmab.
Clinical Trial Registration: NCT03188666 (ClinicalTrials.gov) (LUMINA-1)
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Writing disclosure
Medical writing support under the direction of the authors was provided by Kerren Davenport, BSc, from Prime (Knutsford, UK) according to Good Publication Practice guidelines https://www.acpjournals.org/doi/10.7326/M22-1460 and funded by Regeneron Pharmaceuticals, Inc.
Acknowledgments
The authors thank the patients and their families for their participation in this study, as well as the healthcare professionals and investigators who treated these patients and made this study possible, as well as Richa Attre, PhD, from Regeneron Pharmaceuticals, Inc. for assistance with development of the manuscript.
Financial & competing interests disclosure
Maja Di Rocco: Principal investigator of Regeneron Pharmaceuticals Inc. and Ipsen clinical trials. Robert J Pignolo: Site investigator for Regeneron Pharmaceuticals Inc., Ipsen, and Incyte clinical trials; and chair of the International Clinical Council on FOP (ICC on FOP) Clinical Trials Committee and chair emeritus of the ICC on FOP. Richard Keen: Principal investigator of clinical trials sponsored by Clementia/Ipsen and Regeneron Pharmaceuticals Inc; and non-paid member of the International Clinical Council on FOP and IFOPA registry advisory board. Michelle Davis: Nonpaid member of the Rare Bone Disease Alliance Steering Committee. Philippe Orcel: Principal investigator of clinical trials sponsored by Regeneron Pharmaceuticals Inc. Christian Roux: Research grants from Regeneron Pharmaceuticals Inc. and Alexion. Małgorzata Szczepanek: Speaker for Roche. Javier Bachiller-Corral: Investigator of clinical trial sponsored by Regeneron Pharmaceuticals Inc. Angela M Cheung: Grants to their institution (University Health Network) for clinical trials sponsored by Clementia/Ipsen, Incyte and Regeneron Pharmaceuticals Inc. Kathryn M Dahir: Principal investigator on the Regeneron Pharmaceuticals Inc. LUMINA-1 trial. This project described was supported by CTSA award No. UL1 TR002243 from the National Center for Advancing Translational Sciences. Its contents are solely the responsibility of the authors/sponsor and do not necessarily represent official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. Mona Al Mukaddam: Principal investigator of clinical trials sponsored by Clementia/Ipsen, Regeneron Pharmaceuticals Inc., and Incyte; and a non-paid member of the International Clinical Council on FOP and IFOPA registry advisory board. Dushyanth Srinivasan, Scott J Mellis, Anita Boyapati, Kusha Mohammadi, Aris N Economides, Robert J Sanchez, Dinko Gonzalez Trotter, Susan Rhee, Gary A Herman, Richard DelGizzi, George D Yancopoulos: Employees and shareholders of Regeneron Pharmaceuticals, Inc. E Marelise W Eekhoff: Subsidies/financing FOP research from Dutch FOP Patient Foundation, IFOPA, Regeneron Pharmaceuticals Inc., EU-IMI (AZ), and Clementia/Ipsen; non-paid board memberships for the International Clinical Council on FOP, IFOPA registry advisory board, Dutch Society for Endocrinology (NVE) BoNe; representative for Amsterdam Bone Center and Rare Bone Expert Center, European FOPinvestigators; member of ERN BOND and of an ASBMR committee; and lead clinical principal investigator on the Regeneron Pharmaceuticals Inc. LUMINA-1 trial. Frederick S Kaplan: global principal investigator on the Regeneron Pharmaceuticals Inc. LUMINA-1 and the Clementia/Ipsen MOVE trials.
Competing interests disclosure
Frederick S Kaplan: Founding member and past president of the International Clinical Council on FOP; member of the Medical Advisory Board of the IFOPA Global Registry. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.