537:
small customer base to cut cost on clinical trials due to the small number of cases to have smaller trials which reduces cost. These smaller clinical trials also allow orphan drugs to move to market faster as the average time to receive FDA approval for an orphan drug is 10 months compared to 13 months for non-orphan drugs. This is especially true in the market for cancer drugs, as a 2011 study found that between 2004 and 2010 orphan drug trials were more likely to be smaller and less randomized than their non-orphan counterparts, but still had a higher FDA approval rate, with 15 orphan cancer drugs being approved, while only 12 non-orphan drugs were approved. This allows manufactures to get cost to the point that it is economically feasible to produce these treatments. The subsidies can total up to $ 30 million per fiscal year in the United States alone.
581:(QALY). By 2005 doubts were raised about the use of economic evaluations in orphan drugs. By 2008 most of the orphan drugs appraised had cost-effectiveness thresholds "well in excess of the 'accepted' level and would not be reimbursed according to conventional criteria". As early as 2005 McCabe et al. argued that rarity should not have a premium and orphan drugs should be treated like other pharmaceuticals in general. Drummond et al. argued that the social value of health technologies should also be included in the assessment along with the estimation of the incremental cost-effectiveness ratio.
590:
285:(EU) enacted similar legislation, Regulation(EC) No 141/2000, which refers to drugs developed to treat rare diseases to as "orphan medicinal products". The EU's definition of an orphan condition is broader than that of the US, in that it also covers some tropical diseases that are primarily found in developing nations. Orphan drug status granted by the European Commission gives marketing exclusivity in the EU for 10 years after approval. The EU's legislation is administered by the
76:(EMA) defines a drug as "orphan" if it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically and seriously debilitating condition affecting not more than 5 in 10,000 EU people. EMA also qualifies a drug as orphan if – without incentives – it would be unlikely that marketing the drug in the EU would generate sufficient benefit for the affected people and for the drug manufacturer to justify the investment.
533:(Biogen), FDA approved in December 2016 for spinal muscular atrophy, placing a large amount of stress on insurance companies and patients. An analysis of 12 orphan drugs that were approved in the US between 1990 and 2000 estimated a price reduction of on average 50% upon loss of marketing exclusivity, with a range of price reductions from 14% to 95%.
39:. Examples of this can be that in the U.S. and the EU, it is easier to gain marketing approval for an orphan drug. There may be other financial incentives, such as an extended period of exclusivity, during which the producer has sole rights to market the drug. All are intended to encourage development of drugs which would otherwise lack sufficient
597:
The very large incentives given to pharmaceutical companies to produce orphan drugs have led to the impression that the financial support afforded to make these drugs possible is akin to abuse. Because drugs can be used to treat multiple conditions, companies can take drugs that were filed with their
536:
Governments have implemented steps to reduce high research and development cost with subsidies and other forms of financial assistance. The largest assistance are tax breaks which can be as high as 50% of research and development costs. Orphan drug manufacturers are also able to take advantage of the
359:
While the
European Medicines Agency grants orphan drugs market access in all member states, in practice, they only reach the market when a member state decides that its national health system will reimburse for the drug. For example, in 2008, 44 orphan drugs reached the market in the Netherlands, 35
167:
The 2014 Orphan Drug report stated that the percentage of orphan drug sales as part of all prescription drug sales had been increasing at a rapid rate. The report projected a total of US$ 176 billion by 2020. Although orphan disease populations are the smallest, the cost of per-patient outlays among
355:
was the real cause of this increase, claiming that many of the new drugs were for disorders which were already being researched anyway, and would have had drugs developed regardless of the legislation, and whether the ODA has truly stimulated the production of non-profitable drugs; the act also has
60:(FDA), an orphan drug is defined as one "intended for the treatment, prevention or diagnosis of a rare disease or condition, which is one that affects less than 200,000 persons in the US" (which equates to approximately 6 cases per 10,000 population) "or meets cost recovery provisions of the act".
1271:
In an attempt to simplify the process for obtaining orphan status for medications targeting rare diseases, the FDA and the
European Medicines Agency (EMA) have created a common application. ... U.S. and European regulators still will conduct independent reviews of application submissions to ensure
148:
the revenue-generating potential of orphan drugs as great as for non-orphan drugs, even though patient populations for rare diseases are significantly smaller. Moreover, we suggest that orphan drugs have greater profitability when considered in the full context of developmental drivers, including
84:
In Japan, drugs and medical devices are given the designation as an orphan drug or device based on the Act of
Securing Quality, Efficacy, Safety of Pharmaceuticals, Medical Devices, Regenerative or Cellular Therapy Products, Gene Therapy Products, and Cosmetics if they are intended for use in less
528:
According to a 2015 report published by
EvaluatePharma, the economics of orphan drugs mirrors the economics of the pharmaceutical market as a whole but has a few very large differences. The market for orphan drugs is by definition very small, but while the customer base is drastically smaller the
347:
enacted the ODA in 1983, only 38 drugs were approved in the US specifically to treat orphan diseases. In the US, from
January 1983 to June 2004, 249 orphan drugs received marketing authorization and 1,129 received different orphan drug designations, compared to fewer than ten such products in the
375:
infection. This encouraged the FDA to use the Orphan Drug Act to help bolster research in this field, and by 1995 13 of the 19 drugs approved by the FDA to treat AIDS had received orphan drug designation, with 10 receiving marketing rights. These are in addition to the 70 designated orphan drugs
159:
According to a 2014 report, the orphan drug market has become increasingly lucrative for a number of reasons. The cost of clinical trials for orphan drugs is substantially lower than for other diseases because trial sizes are naturally much smaller than for more diseases with larger numbers of
221:
A 2015 study of "34 key
Canadian stakeholders, including drug regulators, funders, scientists, policy experts, pharmaceutical industry representatives, and patient advocates" investigated factors behind the pharmaceutical industry growing interest in "niche markets" such as orphan drugs.
246:
to develop drugs for diseases that have a small market. Under the ODA drugs, vaccines, and diagnostic agents would qualify for orphan status if they were intended to treat a disease affecting fewer than 200,000 American citizens. Under the ODA orphan drug sponsors qualify for seven-year
163:
Tax incentives reduce the cost of development. On average the cost per patient for orphan drugs is "six times that of non-orphan drugs, a clear indication of their pricing power". The cost of per-person outlays are large and are expected to increase with wider use of public subsidies.
27:
that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by the conditions. The conditions that orphan drugs are used to treat are referred to as
401:, both developed with aid from the ODA, revolutionized treatment for cystic fibrosis patients by significantly improving their quality of life and extending their life expectancies. Now, cystic fibrosis patients often survive into their thirties and some into their fifties.
633:
In 2015, NICE held consultations with "patient groups, the
Department of Health, companies, learned societies, charities and researchers" regarding the appraisal of medicines and other technologies. There was a call for more research into new processes, including:
141:(CAGR) of the orphan drugs was an "impressive 25.8%, compared to only 20.1% for a matched control group of non-orphan drugs". By 2012, the market for orphan drugs was worth US$ 637 million, compared with US$ 638 million for a control group of non-orphan drugs.
638:
the model of pharmaceutical research and development, the expectations that companies and patient groups have about how risk and reward is shared between the industry and a publicly funded NHS, and in the arrangements for commissioning expensive new
504:
Center for Rare
Disease Therapies (CRDT) in Claremont, California, supports projects to revive potential orphan drugs whose development has stalled by identifying barriers to commercialization, such as problems with formulation and bio-processing.
576:
to calculate the ratio of cost to QALYs saved for a particular health care intervention. By 2008 the
National Institute for Health and Care Excellence (NICE) in England and Wales, for example, operated with a threshold range of £20,000–30,000 per
1417:
192:, stability, safety and efficacy. However, some statistical burdens are lessened to maintain development momentum. For example, orphan drug regulations generally acknowledge the fact that it may not be possible to test 1,000 patients in a
614:. After the drug was approved for orphan drug designation, and AstraZeneca had received tax breaks and other advantages, AstraZeneca later applied and received FDA approval for the drug to be used to treat cholesterol in all diabetics.
472:(Onpattro) orphan drug status and breakthrough therapy designation due to its novel mechanism involving RNA therapy to block the production of an abnormal form of transthyretin. Patisiran received full FDA approval in 2018 and its RNA
348:
decade prior to 1983. From 1983 until May 2010, the FDA approved 353 orphan drugs and granted orphan designations to 2,116 compounds. As of 2010, 200 of the roughly 7,000 officially designated orphan diseases have become treatable.
529:
cost of research and development is very much the same as for non orphan drugs. This, the producers have claimed, causes them to charge extremely high amounts for treatment, sometimes as high as $ 700,000 a year, as in the case of
571:
By 2007 the use of economic evaluation methods regarding public-funding of orphan drugs, using estimates of the incremental cost-effectiveness, for example, became more established internationally. The QALY has often been used in
296:
In late 2007 the FDA and EMA agreed to use a common application process for both agencies to make it easier for manufacturers to apply for orphan drug status but, while continuing two separate approval processes.
548:
Public resources went into understanding the molecular basis of the disease, public resources went into the technology to make antibodies and finally, Alexion, to their credit, kind of picked up the pieces.
137:, the years 2001 to 2011 were the "most productive period in the history of orphan drug development, in terms of average annual orphan drug designations and orphan drug approvals". For the same decade the
1425:
1255:
1750:
970:
493:
247:
FDA-administered market Orphan Drug
Exclusivity (ODE), "tax credits of up to 50% of R&D costs, R&D grants, waived FDA fees, protocol assistance and may get clinical trial
305:
Legislation has been implemented by Japan, Singapore, and Australia that offers subsidies and other incentives to encourage the development of drugs that treat orphan diseases.
32:. The assignment of orphan status to a disease and to drugs developed to treat it is a matter of public policy that depends on the legislation (if there is any) of the country.
1301:
Andrew Duffy (23 February 2002). "ORPHAN DISEASES A RARE OCCURRENCE: A desperate search for help; County family joins long list with rare diseases in seeking a miracle".
1278:
500:
College of Pharmacy helps small companies with insufficient in-house expertise and resources in drug synthesis, formulation, pharmacometrics, and bio-analysis. The
371:. In the beginning of the AIDS epidemic the lack of treatment for the disease was often accredited to a believed lack of commercial base for a medication linked to
124:
in their 2012 publication "The Economic Power of Orphan Drugs", there has been increased investment in orphan drug research and development, partly due to the U.S.
2028:
1673:"How pharmaceutical company Alexion set the price of the world's most expensive drug: Cost of one of world's most expensive drugs shrouded in corporate secrecy"
1448:
848:
Giannuzzi, Viviana; Conte, Rosa; Landi, Annalisa; Ottomano, Serena Antonella; Bonifazi, Donato; Baiardi, Paola; Bonifazi, Fedele; Ceci, Adriana (3 April 2017).
1672:
1587:
Meekings, Kiran N.; Williams, Cory S. M.; Arrowsmith, John E. (2012-07-01). "Orphan drug development: an economically viable strategy for biopharma R&D".
544:, was not related to research, development and manufacturing costs. Their price is arbitrary and they have become more profitable than traditional medicines.
1172:
Illingworth, Patricia; Cohen, Jillian; Illingworth, P (2004). "Orphan Drug Policies: Implications for the United States, Canada, and Developing Countries".
1315:
168:
them are the largest and are expected to increase as more people with rare diseases become eligible for subsidies – in the U.S., for example, through the
1973:
254:
In the U.S., orphan drug designation means that the sponsor qualifies for certain benefits, but it does not mean the drug is safe, effective or legal.
623:
35:
Designation of a drug as an orphan drug has yielded medical breakthroughs that might not otherwise have been achieved, due to the economics of drug
938:
850:"Orphan medicinal products in Europe and United States to cover needs of patients with rare diseases: an increased common effort is to be foreseen"
93:
As of 2014, there were 281 marketed orphan drugs and more than 400 orphan-designated drugs in clinical trials. More than 60% of orphan drugs were
2018:
553:
356:
been criticised for allowing some pharmaceutical companies to make a large profit off drugs which have a small market but sell for a high price.
1855:
McCabe, C; Tsuchiya, A; Claxton, K; Raftery, J. (2007). "Assessing the economic challenges posed by orphan drugs: a comment on Drummond et al".
1714:
457:
432:, a rare hereditary disease that can lead to a fatal accumulation of copper in the body. This drug was later found to be effective in treating
2004:
1754:
520:
have been founded in order to advocate on behalf of patients with rare diseases with a particular emphasis on diseases that affect children.
1327:
Denis, Alain; Mergaert, Lut; Fostier, Christel; et al. (2010). "Issues Surrounding Orphan Disease and Orphan Drug Policies in Europe".
593:
Rosuvastatin (brand name Crestor) is an example of a drug that received Orphan Drug funding but was later marketed to a large consumer base.
981:
1418:"US FDA Grants Orphan Drug Designation for Retrotope's RT001 in the Treatment of Phospholipase 2G6 (PLA2G6)-Associated Neurodegeneration"
169:
2023:
1142:
180:
Orphan drugs generally follow the same regulatory development path as any other pharmaceutical product, in which testing focuses on
517:
509:
239:
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government financial incentives, smaller clinical trial sizes, shorter clinical trial times and higher rates of regulatory success.
1371:
1728:
665:
286:
1275:
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government agency as orphan drugs to receive financial assistance, and then market it to a wide population to increase their
670:
477:
516:, Children's Rare Disease Network, Abetalipoproteinemia Collaboration Foundation, Zellweger Baby Support Network, and the
334:
907:
1316:
https://www0.gsb.columbia.edu/mygsb/faculty/research/pubfiles/4716/Lichtenberg%20Orphan%20drugs%20SSRN%202011-01-10.pdf
1115:
1272:
the data submitted meet the legal and scientific requirements of their respective jurisdictions, the agencies said.
160:
patients. Small clinical trials and minimal competition place orphan agents at an advantage in regulatory review.
2068:
2058:
1200:"Orphan disease definition - Medical Dictionary definitions of popular medical terms easily defined on MedTerms"
437:
611:
540:
By 2015, industry analysts and academic researchers agreed, that the sky-high price of orphan drugs, such as
410:
766:
57:
413:, which causes large and rapid increases in cholesterol levels. Their research led to the development of
360:
in Belgium, and 28 in Sweden, while in 2007, 35 such drugs reached the market in France and 23 in Italy.
138:
1057:"Why the Shift? Taking a Closer Look at the Growing Interest in Niche Markets and Personalized Medicine"
340:
The Pharmaceutical Executive opines, that the "ODA is nearly universally acknowledged to be a success".
2048:
721:
627:
578:
2063:
290:
262:
258:
128:(ODA) and similar acts in other regions of the world driven by "high-profile philanthropic funding".
73:
630:) for treatments of "very rare conditions". This is compared to under £20,000 for non-orphan drugs.
111:
Number of orphan drugs in U.S. clinical trials: 350 in the pipeline from research until registration
481:
473:
94:
1508:
313:
Under the ODA and EU legislation, many orphan drugs have been developed, including drugs to treat
2053:
501:
497:
266:
125:
97:. The U.S. dominated development of orphan drugs, with more than 300 trials, followed by Europe.
1624:"Characteristics of clinical trials to support approval of orphan vs nonorphan drugs for cancer"
2073:
1199:
344:
243:
2013:
2043:
573:
1222:"EU Marketing Authorisation of Orphan Medicinal Products and Its Impact on Related Research"
751:
Rich Daly (5 September 2002). "House Offers Incentives For Development of 'Orphan' Drugs".
513:
133:
363:
Though not technically an orphan disease, research and development into the treatment for
8:
2009:
429:
1949:
1926:
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1105:
1081:
1056:
884:
849:
822:
789:
1779:
Drummond, Michael F. (2008). "Challenges in the economic evaluation of orphan drugs".
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The 1985 Nobel Prize for medicine went to two researchers for their work related to
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1911:
1864:
1822:
1814:
1635:
1596:
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1546:
1449:"FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease"
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1023:
879:
861:
817:
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660:
352:
318:
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Creating a government-run enterprise to engage in research and development as in a
185:
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98:
36:
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Government intervention on behalf of orphan drug development takes several forms:
1600:
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1027:
1011:
390:
368:
326:
322:
231:
121:
29:
1012:"Orphan drug development: an economically viable strategy for biopharma R&D"
1010:
Meeking, Kiran N.; Williams, Cory S. M.; Arrowsmith, John E. (15 August 2012),
282:
193:
69:
1868:
1818:
1372:"Rare Diseases, Drug Development, and AIDS: The Impact of the Orphan Drug Act"
1240:
866:
269:. It also increased funding for the development of treatments for people with
2037:
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908:"Ministry of Health, Labour and Welfare: Pharmaceuticals and Medical Devices"
875:
813:
599:
425:
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248:
235:
203:
40:
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1974:"NICE calls for a new approach to managing the entry of drugs into the NHS"
1935:
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1900:"Pricing and reimbursement of orphan drugs: the need for more transparency"
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893:
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1535:"Estimating the budget impact of orphan medicines in Europe: 2010 - 2020"
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is currently under investigation as a therapy against Wilson's disease.
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24:
85:
than 50,000 patients in Japan for which there is a high medical need.
1072:
805:
469:
433:
394:
1477:
Wechsler, Jill (July 2008). "Celebrating 25 Years of Orphan Drugs".
1387:
790:"The current status of orphan drug development in Europe and the US"
530:
2024:
USA Food and Drug Administration: The Orphan Drug Act (as amended)
443:
414:
1055:
Shannon Gibson; Hamid R Raziee; Trudo Lemmens (19 March 2015).
463:
453:
314:
189:
1857:
International Journal of Technology Assessment in Health Care
1509:"Costly Drug for Fatal Muscular Disease Wins F.D.A. Approval"
449:
208:
Exclusivity (enhanced patent protection and marketing rights)
1854:
1370:
Arno, Peter S.; Bonuck, Karen; Davis, Michael (1995-01-01).
1171:
1005:
1003:
1001:
847:
364:
101:
was the indication in more than 30% of orphan drug trials.
1729:"Measuring effectiveness and cost effectiveness: the QALY"
1586:
940:
Global orphan drug market to reach US$ 120 billion by 2018
1997:
1622:
Kesselheim, A. S.; Myers, J. A.; Avorn, J. (2011-06-08).
1533:
Schey, Carina; Milanova, Tsveta; Hutchings, Adam (2011).
1009:
372:
115:
998:
968:
767:"Developing Products for Rare Diseases & Conditions"
610:
was filed as a treatment for the rare disease pediatric
1701:
International Trends in the Use of Health Economic Data
417:
which are now commonly used to treat high cholesterol.
196:
if fewer than that number are affected by the disease.
2005:
DIA/FDA Orphan Drug Designation Workshop November 2010
1532:
1800:
1703:, Spectrum Report, Decision Resources, Waltham, Mass.
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962:
960:
715:
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711:
709:
707:
43:
to attract corporate research budgets and personnel.
1621:
1326:
242:
and many other organizations, is meant to encourage
1751:"Guide to the methods of technology appraisal 2013"
1048:
769:. US Food and Drug Administration. 20 December 2018
626:(NICE) can pay from £100,000 to £300,000 per QALY (
1774:
1772:
957:
704:
696:Armstrong, Walter (May 2010). "Pharma's Orphans".
393:rarely lived beyond their early teens. Drugs like
695:
624:National Institute for Health and Care Excellence
379:
2035:
2029:US FDA List of Orphan Designations and Approvals
1694:
1692:
1256:"U.S., EU Will Use Same Orphan Drug Application"
404:
1769:
1698:
1369:
1220:Gerke, Sara; Pattinson, Shaun D. (2017-02-09).
1106:"Orphan Drug Law Matures into Medical Mainstay"
376:designed to treat other HIV related illnesses.
1850:
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1846:
1796:
1794:
1664:
1476:
1219:
444:Phospholipase 2G6-associated neurodegeneration
1689:
1491:
1472:
1470:
719:
487:
105:Number of orphan drugs in clinical trials: 40
1801:McCabe, C; Claxton, K; Tsuchiya, A. (2005).
1300:
933:
931:
929:
927:
788:Hall, Anthony K; Carlson, Marilyn R (2014).
464:Transthyretin-related hereditary amyloidosis
452:orphan drug designation in the treatment of
108:Number of orphan drugs in phase 2 trial: 231
1843:
1791:
1253:
787:
746:
744:
691:
689:
687:
685:
476:drug delivery system was later used in the
1713:: CS1 maint: location missing publisher (
1467:
1329:Applied Health Economics and Health Policy
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1966:
1925:
1915:
1826:
1721:
1639:
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1080:
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1976:(Press release). NICE. 18 September 2014
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682:
588:
510:National Organization for Rare Disorders
240:National Organization for Rare Disorders
1897:
1582:
1580:
1287:
1140:
946:, New Delhi: Kuick Research, 7 Feb 2014
720:Hadjivasiliou, Andreas (October 2014),
666:European Organization for Rare Diseases
351:Critics have questioned whether orphan
308:
16:Regulatory class of pharmaceutical drug
2036:
1506:
1494:EvaluatePharma Orphan Drug Report 2015
1446:
1167:
1165:
1136:
1134:
1132:
1103:
1097:
843:
841:
794:Intractable and Rare Diseases Research
566:
287:Committee on Orphan Medicinal Products
116:Effect on investment, sales and profit
1699:Drummond, M. F.; Grubert, N. (2007),
1670:
753:Congressional Quarterly Daily Monitor
518:Friedreich's Ataxia Research Alliance
508:Numerous advocacy groups such as the
234:(ODA) of January 1983, passed in the
1731:(Press release). NICE. 20 April 2010
1577:
971:"The Economic Power of Orphan Drugs"
759:
671:Supplementary protection certificate
261:was signed into law. It amended the
88:
1162:
1129:
969:Laura Gaze; Jennifer Breen (2012),
838:
781:
420:
335:idiopathic thrombocytopenic purpura
13:
1950:"Our charter | Who we are | About"
1507:Thomas, Katie (30 December 2016).
584:
384:
300:
225:
14:
2085:
1991:
1904:Orphanet Journal of Rare Diseases
1539:Orphanet Journal of Rare Diseases
1424:. 2 November 2017. Archived from
1141:Pollack, Andrew (30 April 1990).
1116:U.S. Food and Drug Administration
1061:World Medical & Health Policy
854:Orphanet Journal of Rare Diseases
561:
276:
1455:. US Federal Drug Administration
1447:Brooks, Megan (10 August 2018).
1341:10.2165/11536990-000000000-00000
478:Pfizer–BioNTech COVID-19 vaccine
51:
1942:
1891:
1743:
1615:
1526:
1500:
1492:Hadjivasiliou, Andreas (2015).
1485:
1440:
1410:
1363:
1320:
1309:
1213:
1192:
494:Center for Orphan Drug Research
456:-associated neurodegeneration (
367:has been heavily linked to the
1898:Simoens, Steven (2011-06-17).
1229:European Journal of Health Law
1143:"Orphan Drug Law Spurs Debate"
900:
438:Bis-choline tetrathiomolybdate
380:Examples for selected diseases
175:
1:
2019:List of European Orphan Drugs
1671:Crowe, Kelly (25 June 2015),
676:
612:familial hypercholesterolemia
411:familial hypercholesterolemia
405:Familial hypercholesterolemia
46:
1998:Drug Information Association
1753:. NICE. 2013. Archived from
1601:10.1016/j.drudis.2012.02.005
1028:10.1016/j.drudis.2012.02.005
58:Food and Drug Administration
7:
649:
139:compound annual growth rate
10:
2090:
1803:"Orphan drugs and the NHS"
1254:Donna Young (2007-11-28).
1202:. Medterms.com. 2002-08-25
628:Quality Adjusted Life Year
579:quality-adjusted life year
488:Activism, research centers
389:In the 1980s, people with
2014:The Orphan drugs strategy
1869:10.1017/s0266462307071012
1819:10.1136/bmj.331.7523.1016
1479:Pharmaceutical Technology
1241:10.1163/15718093-12341439
867:10.1186/s13023-017-0617-1
722:"Orphan Drug Report 2014"
291:European Medicines Agency
263:Public Health Service Act
238:, with lobbying from the
74:European Medicines Agency
63:
698:Pharmaceutical Executive
244:pharmaceutical companies
194:phase III clinical trial
79:
37:research and development
1807:British Medical Journal
617:
523:
502:Keck Graduate Institute
498:University of Minnesota
428:was developed to treat
267:Office of Rare Diseases
126:Orphan Drug Act of 1983
2069:Life sciences industry
2059:Pharmaceuticals policy
1917:10.1186/1750-1172-6-42
1552:10.1186/1750-1172-6-62
1303:Windsor Star (Ontario)
647:
594:
559:
157:
1641:10.1001/jama.2011.769
1376:The Milbank Quarterly
1104:Henkel, John (1999).
636:
592:
574:cost-utility analysis
546:
448:In 2017, FDA granted
146:
1589:Drug Discovery Today
1016:Drug Discovery Today
606:'s cholesterol drug
514:Global Genes Project
309:Numbers of new drugs
134:Drug Discovery Today
56:According to the US
25:pharmaceutical agent
2010:European Commission
567:Evaluation criteria
170:Affordable Care Act
154:Gaze and Breen 2012
1595:(13–14): 660–664.
1513:The New York Times
1281:2008-03-09 at the
1174:Health Law Journal
1148:The New York Times
1022:(13–14): 660–664,
595:
474:lipid nanoparticle
211:Research subsidies
2049:Biotechnology law
1634:(22): 2320–2326.
1496:. EvaulatePharma.
454:phospholipase 2G6
265:to establish the
259:Rare Diseases Act
216:Crown corporation
89:Global statistics
2081:
2064:Health economics
1986:
1985:
1983:
1981:
1970:
1964:
1963:
1961:
1960:
1946:
1940:
1939:
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693:
661:Drug development
645:
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468:The FDA granted
430:Wilson's disease
421:Wilson's disease
353:drug legislation
319:multiple myeloma
186:pharmacodynamics
182:pharmacokinetics
155:
99:Cancer treatment
2089:
2088:
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2083:
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1994:
1989:
1979:
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1429:
1428:on 1 April 2019
1422:Global Newswire
1416:
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1388:10.2307/3350258
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1283:Wayback Machine
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391:cystic fibrosis
387:
385:Cystic fibrosis
382:
369:Orphan Drug Act
333:poisoning, and
327:phenylketonuria
323:cystic fibrosis
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301:Other countries
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232:Orphan Drug Act
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118:
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1992:External links
1990:
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1154:15 February
1121:14 February
1067:(1): 3–27.
773:28 December
639:treatments.
604:AstraZeneca
345:US Congress
343:Before the
331:snake venom
176:Legislation
21:orphan drug
2038:Categories
1959:2021-03-29
1781:Eurohealth
1545:(62): 62.
1266:2008-01-06
1206:2010-06-07
917:2023-01-11
800:(1): 1–7.
677:References
542:eculizumab
399:tobramycin
72:(EU), the
47:Definition
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814:2186-3644
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622:The UK's
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434:arthritis
395:Pulmozyme
144:By 2012,
95:biologics
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1709:citation
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1658:21642684
1609:22366309
1571:21951518
1518:12 April
1432:12 March
1357:27388954
1349:20804226
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950:20 March
894:28372595
832:25343119
650:See also
642:—
551:—
531:Spinraza
152:—
2003:EVENT:
1980:29 June
1927:3132155
1828:1273462
1682:25 June
1562:3191371
1453:fda.gov
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1276:Alt URL
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1041:29 June
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608:Crestor
496:at the
482:Moderna
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1982:2015
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1932:PMID
1873:PMID
1833:PMID
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1737:2015
1715:link
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1654:PMID
1646:ISSN
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1605:PMID
1567:PMID
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524:Cost
492:The
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