Duchenne muscular dystrophy (DMD) is one of the most common and devastating types of muscular degeneration and results in progressive muscle weakness starting at an early age1,2
DMD is a genetic, degenerative disease that is inherited in an X-linked recessive mode with an incidence of up to 1 in 3,500 live born males worldwide.1–4 The average age of symptoms onset is between 3 and 5 years, with patients experiencing progressive weakness of muscles, usually leading to the loss of ambulation as teenagers.1,3,5
DMD is characterized by a loss of the protein dystrophin, leading to cell damage, impaired calcium homeostasis, elevated oxidative stress and reduced energy production in muscle cells.3,4 This results in progressive muscle weakness, loss of muscle tissue and early morbidity and mortality due to cardio-respiratory failure.2–4, 6–13 Progressive respiratory muscle weakness leads to restrictive respiratory disease, hypoventilation, ineffective cough, recurrent pulmonary infections, atelectasis, respiratory failure and ultimately the need for daytime ventilation.14–16 As respiratory insufficiency develops, mechanical ventilation becomes necessary to prolong survival beyond the late-teenage years.2,6,13,17
New treatments are urgently needed to slow disease progression in patients with DMD
Currently, glucocorticoids are the only available medical treatment that can slow the decline in muscle strength and function, irrespective of the disease-causing mutation.3,5,13,17,18 However, the effect is only partial and clinical use is limited by well-known side effects caused by steroids.3,5,13,17,18 A recent study showed that up to 42% of DMD patients aged 10 years and older had either never used steroids or have discontinued their use.5 Loss of respiratory function with increasing age continues to be a major cause of morbidity and mortality in patients with DMD, and new treatments to support respiratory function are needed urgently.2,6,13,17
Santhera has partnered with Parent Project Muscular Dystrophy (PPMD) to study patient and caregiver preferences regarding the benefits and risks of pulmonary therapies in DMD. Please click here to find out more about this project.
Raxone clinical development in DMD
Santhera’s clinical development program with Raxone in DMD started with a Phase II randomized, placebo-controlled trial (the DELPHI trial).19,20
The DELOS trial evaluated the efficacy and safety of Raxone in delaying the loss of respiratory function in patients with DMD compared with placebo.5 DELOS was a double-blind, randomized, placebo-controlled Phase III study in patients with DMD aged between 10 and 18 years who were not using concomitant corticosteroids.6 The results of the DELOS trial have been published in The Lancet, Neuromuscular Disorders and Pediatric Pulmonology. 6,20,21
Santhera has been granted orphan drug designation for Raxone for the treatment of DMD in Europe and the US. The US Food and Drug Administration (FDA) has also granted rare pediatric disease designation and Fast Track designation for Raxone for the treatment of DMD. Furthermore, the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) designated Raxone as Promising Innovative Medicine (PIM) and as a suitable candidate for entry into Step II of the EAMS process.
Santhera has filed a Marketing Authorization Application in the European Union and in Switzerland for Raxone for the treatment of DMD.
Mendell JR & Lloyd-Puryear M. Muscle Nerve 2013; 48:21–26.
Passamano L, et al. Acta Myol 2012; 31:121–125.
Bushby K, et al. Lancet Neurol 2010; 9:77–93.
Timpani CA, et al. Med Hypotheses 2015 ; 85:1021–1033.
Henricson EK, et al. Muscle Nerve 2013; 48:55–67.
Buyse GM et al. The Lancet 2015; 385:1748–1757.
Inkley SR, et al. Am J Med 1974; 56:297–306.
Rideau RY, et al. Muscle Nerve 1981; 4:155–164.
McDonald CM, et al. Am J Phys Med Rehabil 1995; 74:S70–S92.
Tangsrud S, et al. Resp Med 2001; 95:898–903.
Kohler M, et al. Am J Respir Crit Care Med 2005; 172:1032–1036.
Bushby K, et al. Lancet Neurol 2010; 9:177–189.
Buyse GM, et al. Eur Neurol Rev 2015; 10:189–194.
Melacini P, et al. Neuromuscul Disord 1996; 6:367–376.
Simonds AK. Semin Respir Crit Care Med 2002; 23:231–238.
Bourke SC. Clin Med 2014; 14:72–75.
LoMauro A, et al. Ther Clin Risk Manag 2015; 11:1475–1488.
Ricotti V, et al. J Neurol Neurosurg Psychiatry 2013; 84:698–705.
Buyse GM, et al. Neuromusc Disord 2011; 21:396–405.
Buyse GM, et al. Pediatr Pulmonol 2013; 48:912–920.
McDonald et al. Neuromuscular Disorders 2016, 26: 473-480