Novel treatments for rare rheumatologic disorders: analysis of the impact of 30 years of the US orphan drug act

Thomas Lutz; Anette Lampert; Georg F. Hoffmann; Markus Ries

doi:10.1186/s13023-016-0443-x

Orphanet Journal of Rare Diseases

Table 2 Orphan drugs for the treatment of rare rheumatologic disorders approved by the FDA between 1983 and 2013

From: Novel treatments for rare rheumatologic disorders: analysis of the impact of 30 years of the US orphan drug act

Compound	Approved indication according to FDA label	Pharmacologic category	Designation year	Approval year	Pivotal clinical trial					Reference
Compound	Approved indication according to FDA label	Pharmacologic category	Designation year	Approval year	Study design	N	Age	Study duration	Main outcome measure	Reference
Pilocarpine hydrochloride	Treatment of dry mouth in patients with Sjögren’s syndrome	Cholinergic agonist	1992	1998	RCT	256	mean 57 years (24 – 85)	12 weeks	Global improvement of dry mouth	[26]
Pilocarpine hydrochloride	Treatment of dry mouth in patients with Sjögren’s syndrome	Cholinergic agonist	1992	1998	RCT	373	mean 55 years (21 – 84)	12 weeks	Global improvement of dry mouth	[26]
Etanercept	Reduction in signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in patients who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs	Tumor necrosis factor-alpha inhibitor	1998	1999	RCT	69	2 – 17 years	7 months	JIA definition of improvement criteria	[10]
Dexamethasone (intravitreal implant)	Treatment of non-infectious uveitis affecting the posterior segment of the eye	Glucocorticoid	1998	2010	RCT	153	n/a	8 weeks	Vitreous haze score and 3-line improvement from baseline in best corrected visual acuity	[27]
Fluocinolone acetonide (intravitreal implant)	Treatment of chronic non-infectious uveitis affecting the posterior segment of the eye	Glucocorticoid	2000	2005	RCT	108	n/a	3 years	Rate of recurrence of uveitis affecting the posterior segment of the study eye	[28]
Fluocinolone acetonide (intravitreal implant)		Glucocorticoid	2000	2005	RCT	116	n/a	3 years	Rate of recurrence of uveitis affecting the posterior segment of the study eye	[28]
Meloxicam	For relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients 2 years of age or older	NSAID	2002	2005	RCT	n/a	≥2 years	12 weeks	ACR Pediatric 30	[29]
Meloxicam		NSAID	2002	2005	RCT	n/a	≥2 years	12 weeks	ACR Pediatric 30	[29]
Rilonacept	Treatment of cryopyrin-associated periodic syndromes	Interleukin inhibitor	2004	2008	RCT	47	n/a	24 weeks	CAPS symptom score	[30]
Adalimumab	Treatment of juvenile idiopathic arthritis	Tumor necrosis factor-alpha inhibitor	2005	2008	RCT	171	4 – 17 years	32 weeks	ACR Pediatric 30	[31]
Adalimumab	Treatment of juvenile idiopathic arthritis	Tumor necrosis factor-alpha inhibitor	2005	2008	OL	32	2 – ≤ 4 years or ≥ 4 years weighing < 15 kg	120 weeks	Safety	[31]
Rituximab	For the use in combination with glucocorticoids for the treatment of patients with Wegener’s granulomatosis and microscopic polyangiitis	Selective immunosuppressant	2006	2011	RCT	197	≥15 years	18 months	Birmingham Vasculitis Activity Score for Granulomatosis with Polyangiitis	[16]
Colchicine	Treatment of familial Mediterranean fever	Mitotic poison	2007	2009	Evidence for the efficacy was derived from the published literature.					[32]
					RCT	15	n/a	n/a	n/a
					RCT	22	n/a	n/a	n/a
Canakinumab	Treatment of cryopyrin-associated periodic syndromes, in adults and children 4 years of age and older	Interleukin inhibitor	2007	2009	RCT	31	9 – 74 years	8 weeks	Minimal or better for physician’s assessment of disease activity, assessment of skin disease, and serum levels of C-Reactive Protein and Serum Amyloid A	[19]
Canakinumab		Interleukin inhibitor	2007	2009	OL	n/a	4 – 74 years		n/a	[19]
Canakinumab	Treatment of active systemic juvenile idiopathic arthritis in patients aged 2 through 16 years	Interleukin inhibitor	2008	2013	RCT	84	mean 8.5 years (2 – 20)	4 weeks	Adapted ACR Pediatric 30 and absence of fever	[19]
Canakinumab		Interleukin inhibitor	2008	2013	RCT	177	mean 8.5 years (2 – 20)	n/a	ACR Pediatric 30	[19]
Difluprednate (ophthalmic solution)	Treatment of endogenous anterior uveitis	Glucocorticoid	2008	2012	RCT	110	n/a	2 weeks	Difference in anterior chamber cell grade	[33]
Difluprednate (ophthalmic solution)	Treatment of endogenous anterior uveitis	Glucocorticoid	2008	2012	RCT	90	n/a	2 weeks	Difference in anterior chamber cell grade	[33]
Anakinra	Treatment of neonatal-onset multisystem inflammatory disease	Interleukin inhibitor	2010	2012	OL	43	0.7 – 46 years	60 months	disease-specific Diary Symptom Sum Score	[34]
Tocilizumab	Treatment of active polyarticular juvenile idiopathic arthritis in patients 2 through 16 years of age	Interleukin inhibitor	2012	2013	RCT	188	2 – 17 years	24 weeks	JIA ACR 30 flare	[20]

ACR Pediatric 30 American College of Rheumatology Pediatric 30 response, CAPS Cryopyrin-associated periodic syndromes, JIA Juvenile idiopathic arthritis, JIA ACR 30 flare Juvenile idiopathic arthritis American College of Rheumatology 30 flare, JRA Juvenile rheumatoid arthritis, n/a not applicable or no information is provided in the FDA label, NSAID Nonsteroidal anti-inflammatory drugs, OL Open label, RCT Randomized controlled trial, uncontrolled, SJIA Systemic juvenile idiopathic arthritis

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