Prescription drugs first approved outside the USA with novel mechanisms, 2001–2010
| Prescription drug | First approval date (agency) | Lag until FDA approval (days) | Mechanism | Main indication(s) | Orphan?* | Alternative therapeutic class(es) available in the USA?† | Outcome of first FDA submission‡ |
|---|---|---|---|---|---|---|---|
| Agalsidase alfa (Replagal) | 3/29/01 (EMA) | NA | Agalsidase alfa replacement | Fabry disease | Yes | No | Withdrawn by sponsor |
| Agalsidase beta (Fabrazyme) | 3/29/01 (EMA) | 756 | Agalsidase beta replacement | Fabry disease | Yes | No | Not approved—efficacy |
| Agomelatine (Thymanax) | 11/20/08 (EMA) | NA | Mixed melatonin agonist/serotonin receptor antagonist | Depression | No | Yes§ | Never filed |
| Alemtuzumab (Campath) | 3/28/01 (EMA) | 40 | Anti-CD52 antibody | Leukaemia (CLL) | Yes | Yes** | Not approved—efficacy |
| Alglucosidase alfa (Myozyme) | 1/26/06 (EMA) | 92 | Alglucosidase alfa replacement | Pompe disease | Yes | No | Approved |
| Artemether/lumefantrine (Coartem) | 11/28/00 (EMA) | 3052 | Artimesenin antiparasitic (artemether); poorly defined (lumefantrine) | Malaria | Yes | Yes1 | Approved |
| Carglumic acid (Carbaglu) | 10/17/02 (EMA) | 2709 | Carbamoyl phosphate synthetase 1 activator | N-acetylglutamate synthase deficiency | Yes | No | Withdrawn by sponsor |
| Catumaxomab (Removab) | 2/19/09 (EMA) | NA | Anti-EpCAM/CD3 antibody | Malignant ascites | No2 | Yes3 | Never filed |
| Denosumab (Prolia) | 12/17/09 (EMA) | 166 | Anti-RANKL antibody | Osteoporosis | No | Yes§ | Not approved—safety |
| Histamine dihydrochloride (Ceplene) | 7/24/08 (EMA) | NA | Therapeutic histamine receptor agonist | Leukaemia (AML) | Yes | Yes§ | Not approved—efficacy |
| Icatibant (Firazyr) | 4/24/08 (EMA) | 1218 | Selective bradykinin B2-receptor antagonist | Hereditary angio-oedema | Yes | No | Not approved—efficacy |
| Idebenone (Catena) | 7/23/08 (HC)†† | NA | Antioxidant/coenzyme Q10 analogue¶ | Friedreich's ataxia | Yes | No | Never filed |
| Ivabradine (Corlentor) | 7/27/05 (EMA) | 3548 | Selective sinoatrial pacemaker modulating f-current inhibitor | Heart failure | No | Yes§ | Approved |
| Laronidase (Aldurazyme) | 2/20/03 (EMA) | 69 | Laronidase replacement | Mucopolysaccharidosis type 1 | Yes | No | Approved |
| Laropiprant/nicotinic acid (Pelzont) | 4/24/08 (EMA)†† | NA | Combined DGAT2/DP1 antagonist | Dyslipidaema | No | Yes§ | Not approved—safety |
| Maraviroc (Selzentry) | 7/19/07 (EMA) | 18 | CCR5 antagonist | HIV | No | Yes§ | Approved |
| Methylnaltrexone bromide (Relistor) | 3/28/08 (HC) | 27 | Peripherally acting opioid antagonist | Opioid-induced constipation | Yes | Yes4 | Approved |
| Mifamurtide (Mepact) | 12/18/08 (EMA) | NA | NOD2 agonist | Osteosarcoma | Yes | Yes** | Not approved—efficacy5 |
| Miglustat (Zavesca) | 7/25/02 (EMA) | 371 | Glucosylceramide synthase inhibitor | Gaucher disease | Yes | Yes6 | Not approved—safety |
| Omega-3 fatty acid ethyl esters (Lovaza) | 3/4/03 (EMA) | 617 | Poorly defined††¶ | Hypertriglyceridaemia | No | Yes§ | Approved |
| Pegvisomant (Somavert) | 7/25/02 (EMA) | 243 | GH receptor antagonist | Acromegaly | Yes | Yes7 | Not approved—safety |
| Pirfenidone (Esbriet) | 12/16/10 (EMA) | 1399 | Poorly defined†† | Idiopathic pulmonary fibrosis | Yes | No | Not approved—efficacy |
| Porfimer sodium (PhotoBarr) | 7/13/95 (HC) | 167 | Photosensitising agent | Cancers/dysplasias (various) | Yes | No | Approved |
| Rimonabant (Accomplia) | 4/27/06 (EMA)‡‡ | NA | CB-1 receptor antagonist | Obesity | No | Yes8 | Not approved—safety |
| Rivaroxaban (Xarelto) | 7/24/08 (EMA) | 1072 | Direct factor Xa inhibitor | Anticoagulation | No | Yes§ | Not approved—safety |
| Roflumilast (Daxas) | 4/22/10 (EMA) | 312 | PDE4 inhibitor | Chronic obstructive pulmonary disease | No | Yes§ | Not approved—safety |
| Stiripentol (Diacomit) | 10/18/06 (EMA) | NA | Poorly defined†† | Severe myoclonic epilepsy in infants | Yes | Yes§ | Never filed |
| Strontium ranelate (Protelos) | 6/23/04 (EMA) | NA | Poorly defined†† | Osteoporosis | No | Yes§ | Never filed |
| Sugammadex (Bridion) | 5/30/08 (EMA) | 2755 | Rocuronium chelator | Neuromuscular blockade reversal | No | No | Not approved—safety |
| Tegafur/gimeracil/oteracil (Teysuno/S-1) | 12/16/10 (EMA) | NA | Thymidylate synthase inhibitor (tegafur); 5-FU degradation inhibitor (gimeracil); orotate phosphoribosyl-transferase inhibitor (oteracil) | Gastric cancer | Yes | Yes§ | Never filed |
| Tocilizumab (Actemra) | 11/20/08 (EMA) | 414 | Anti-IL-6 antibody | Rheumatoid arthritis | No | Yes§ | Not approved—safety |
| Trabectedin (Yondelis) | 7/19/07 (EMA) | 3018 | Poorly defined†† | Soft tissue sarcomas | Yes | Yes** | Not approved—efficacy |
| Ulipristal acetate (Ella) | 3/19/09 (EMA) | 512 | Mixed progesterone receptor antagonist/agonist | Emergency contraception | No | Yes9 | Approved |
| Ustekinumab (Stelara) | 11/20/08 (EMA) | 309 | Anti-IL-12/IL-23 antibody | Psoriasis | No | Yes§ | Not approved—safety |
| Vernakalant hydrochloride (Brinavess) | 6/24/10 (EMA) | n/a | IKur/IKACh atrial potassium current blocker | Atrial fibrillation | No | Yes§ | Not approved—safety |
| Vigabatrin (Sabril) | 1/14/94 (HC) | 5698 | GABA-T inhibitor | Infantile spasms | Yes | Yes10 | Approved |
| Ziconotide (Prialt) | 11/18/04 (EMA) | 40 | N-type calcium channel inhibitor | Pain | Yes | Yes§ | Not approved—safety |
*By the EMA, FDA and/or HC.
†‘Yes’ indicates that at the time of approval by the EMA and/or HC, at least one therapeutic alternative was available in the USA for main indication.
‡See text for details of definitions.
§Multiple alternative therapies available in the USA for this indication at the time of non-US approval.
¶First approved prescription medicine of this type (as opposed to over-the-counter forms).
**Multiple chemotherapy agents already available in the USA with efficacy in this indication at the time of non-US approval.
††Ill-defined mechanism of action; impossible to identify the pharmacological analogue previously approved in the USA.
‡‡Subsequently withdrawn in some/all regions.
5-FU, fluorouracil; AML, acute myeloid leukaemia; CB-1, cannabinoid receptor type 1; CCR5, C-C chemokine receptor type 5; CD, cluster of differentiation; CLL, chronic lymphocytic leukaemia; DGAT2, diacylglycerol O-acyltransferase 2; DP1, prostaglandin D2 receptor 1; EMA, European Medicines Agency; EpCAM, epithelial cell adhesion molecule; FDA, Food and Drug Administration; GABA-T, γ-aminobutyric acid transaminase; GH, growth hormone; HC, Health Canada; IKAch, G-protein-activated K(+) current; IKur, ultra-rapid outward current; IL, interleukin; NA, not approved in the USA as of 1 May 2016; NOD2, nucleotide-binding oligomerisation domain-containing protein 2; PDE4, phosphodiesterase type 4; RANKL, receptor activator of nuclear factor κ-B ligand.
↵1Atovaquone/proguanil hydrochloride (Malarone) already available in the USA.
↵2EMA granted orphan status for gastric cancer, but drug was never approved for this indication
↵3Therapeutic paracentesis already available as accepted (non-pharmacological) therapeutic option in the USA.
↵4Multiple alternative laxative therapies already available in the USA.
↵5Efficacy implied by sponsor as main rationale for rejection; see http://www.prnewswire.com/news-releases/idm-pharma-receives-not-approvable-letter-for-mifamurtide-l-mtp-pe-for-the-treatment-of-osteosarcoma-58556887.html (accessed 9 September 2016).
↵6Enzyme replacement (imiglucerase (Cerezyme)) already available in the USA.
↵7Octreotide (Sandostatin LAR) already available in the USA.
↵8Orlistat (Xenical) already available in the USA.
↵9Plan B One-Step (levonorgestrel) already available in the USA.
↵10ACTH (adrenocorticotropic hormone) gel already available in the USA.