TABLE 1.

Repurposed orphan medicinal products approved between January 1st, 2016 and December 16th, 2020. CoI: conflict of interest.

Active substance	Therapeutic indication (current therapeutic indication in case of only a “Modified” innovation, otherwise previous therapeutic indication)	Innovation	Trade name	Pharmaceutical form	Start of drug repurposing	ATC Class current indication	References	Remarks
Amikacin sulfate	Infections with Gram-negative and Gram-positive organisms	Indication: Non-tuberculous mycobacterial lung infections	Arikayce liposomal	Nebuliser dispersion	Indication: Academia	J—Antiinfectives for systemic use	Forslöw et al. (2003)	No CoI, acknowledgement suggests no industry funding
		Modified: Liposomal			Modified: Industry		Weers et al. (2009)
Budesonide	Asthma, allergic rhinitis, nasal polyps	Indication: Eosinophilic esophagitis	Jorveza	Orodispersible tablet	Academia	A—Alimentary tract and metabolism	Aceves et al. (2007)	No acknowledgement, CoI describes industry funding
Cannabidiol	Lennox Gastaut syndrome, Dravet syndrome, seizures associated with tuberous sclerosis complex	Indication: Registered for subset of known indications	Epidyolex	Oral solution	Academia	N—Nervous system	Izquierdo et al. (1973)	No CoI, acknowledgement suggests no industry funding
Chenodeoxy-cholic acid	Gallstones	Indication: Cerebrotendinous xanthomatosis	Chenodeoxy-cholic acid Leadiant	Hard capsule	Academia	A—Alimentary tract and metabolism	Salen et al. (1974)	No CoI, acknowledgement suggests no industry funding
Chlormethine	Mycosis fungoides-type cutaneous T-cell lymphoma	Modified: Gel	Ledaga	Gel	Industry	L—Antineoplastic and immunomodulating agents	Lessin et al. (2013)
Ciclosporin	Prevention of graft rejection following solid organ transplantation	Indication: Severe vernal keratoconjunctivitis	Verkazia	Eye drops	Academia	S—Sensory organs	BenEzra et al. (1986)	No full text, no CoI, no acknowledgement
Daunorubicin hydrochloride, cytarabine	Newly diagnosed, therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes	Modified: Combination therapy	Vyxeos liposomal	Powder for concentrate for solution for infusion	Modified: Academia	L—Antineoplastic and immunomodulating agents	Crowther et al. (1970)	No CoI, acknowledgement mentions industry but introduction describes the choice of compounds from academia
		Modified: Combination as liposomal			Modified: Industry		Tardi et al. (2009)
Glibenclamide	Diabetes mellitus type 2	Indication: Neonatal diabetes mellitus	Amglidia	Oral suspension	Academia	A—Alimentary tract and metabolism	Sagen et al. (2004); Zung et al. (2004)	Both: no CoI, acknowledgement describes government funding
Irinotecan hydrochloride trihydrate	Colorectal cancer, small cell lung cancer	Indication: Metastatic adenocarcinoma of the pancreas	Onivyde pegylated liposomal	Concentrate for dispersion for infusion	Academia	L—Antineoplastic and immunomodulating agents	Sakata et al. (1994); Wagener et al. (1995)	Sakata: no full text, no CoI, no acknowledgement. Wagener: No CoI, no acknowledgement
Mercaptamine hydrochloride	Cystinosis	Indication: Corneal cystine crystal deposits	Cystadrops	Eye drops solution	Indication: Academia	S—Sensory organs	Dufier et al. (1987)	No full text, no CoI, no acknowledgement
		Modified: viscous formulation			Modified: Academia		Bozdag et al. (2008)	No CoI, acknowledgement suggests no industry funding
Mexiletine hydrochloride	Ventricular arrhythmias	Incidation: Non-dystrophic myotonic disorders	Namuscla	Hard capsule	Academia	C—Cardiovascular system	Pouget & Serratrice, (1983)	No full text, no CoI, no acknowledgement
Treosulfan	Ovarian cancer	Indication: Conditioning treatment prior to allogeneic haematopoietic stem cell transplantation	Trecondi	Powder for solution for infusion	Industry	L—Antineoplastic and immunomodulating agents	Schmidt-Hieber, (2007)
Treprostinil sodium	Pulmonary arterior hypertension	Indication: WHO functional class III or IV and chronic thromboembolic pulmonary hypertension	Trepulmix	Solution for infusion	Academia	B- Blood and blood forming organs	Skoro-Sajer et al. (2007)	No acknowledgement, CoI describes government funding