Drugs and biologics receiving FDA orphan drug designation: an analysis of the most frequently designated products and their repositioning strategies

Miller, Kathleen L.; Kraft, Selma; Ipe, Abraham; Fermaglich, Lewis J.

doi:10.1080/21678707.2021.2047021

Cited by 11 publications

(13 citation statements)

References 23 publications

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“… 46 There have been 5,099 ODDs and 724 associated drug approvals, comprising both unique and repurposed drugs, since the inception of the program in 1983 until 2019. 47 , 48 We also searched the FDA database Orphan Drug Designations and Approvals and found 1,190 designations and 248 approvals from January 2020 until November 2022 49 suggesting a steady increase in numbers in both categories. Drug approvals span several therapeutic areas and are most concentrated in oncology (34%), followed by metabolic and endocrine (15%) and hematology (11%).…”

Section: Discussionmentioning

confidence: 99%

Successfully Navigating Food and Drug Administration Orphan Drug and Rare Pediatric Disease Designations for AAV9-hPCCA Gene Therapy: The National Institutes of Health Platform Vector Gene Therapy Experience

et al. 2023

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Orphan drug designation (ODD) is an important program intended to facilitate the development of orphan drugs in the United States. An orphan drug benefiting pediatric patients can qualify as a drug for a Rare Pediatric Disease Designation (RPDD) as well. The ODD and RPDD programs provide financial incentives for development of diagnostic drugs, preventive measures, and treatment of diseases affecting small patient populations (adult and pediatric) for which commercial development would otherwise be very challenging. In 2019, a multidisciplinary group of collaborators at National Institutes of Health (NIH) embarked upon a gene therapy platform program called Platform Vector Gene Therapy (PaVe-GT) intended to develop gene therapies for four such rare disorders. An important part of PaVe-GT is to publicly share scientific and regulatory experience gained at different stages during the implementation of the PaVe-GT platform utilizing illustrative examples. The PaVe-GT team recently obtained ODD and RPDD for an adeno-associated virus gene therapy to treat propionic acidemia. Given an increasing interest in obtaining ODD for gene therapy, especially by small companies, research investigators, and patient groups, we overview the submission process and subsequently provide examples of our ODD and RPDD applications. Our ODD and RPDD applications and templates can also be found on the PaVe-GT website. Shared reference documents will have great utility to assist parties who may have limited experience with the preparation of similar applications for their orphan product.

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Section: Discussionmentioning

confidence: 99%

Successfully Navigating Food and Drug Administration Orphan Drug and Rare Pediatric Disease Designations for AAV9-hPCCA Gene Therapy: The National Institutes of Health Platform Vector Gene Therapy Experience

et al. 2023

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“…This issue was also acknowledged by the FDA in 2011, claiming that the ODA precipitated "the creation of subsets of non-rare diseases or conditions that are artificially narrow" (Herder, 2013). Miller and collaborators (2022) provide examples of orphan drugs that have received more than 10 ODDs from a single sponsor, three monoclonal antibodies (brentuximab, nivolumab, and pembrolizumab) and one small molecule, ibrutinib, that target different types of cancer (Miller et al, 2022).…”

Section: Negative Consequences Of the Odamentioning

confidence: 99%

Pharmaceutical policy and innovation for rare diseases: A narrative review

Ruiz

Large²,

Moon³

et al. 2023

F1000Res

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This article aims to synthesize the existing literature on the implementation of public policies to incentivize the development of treatments for rare diseases (which are diseases with very low prevalence and therefore with low commercial interest) otherwise known as orphan drugs. The implementation of these incentives in the 1980s in the United States (US), later in Japan, and in the European Union (EU) seems to be related to a substantial increase in treatments for these diseases, and has influenced the way the pharmaceutical research & development (R&D) system operates beyond this area. In spite of this success, the academic literature also highlights the negative implications that these public policies have on affordability and access to orphan drugs, as well as on the prioritization of certain rare disease areas over others. The synthesis focuses mostly on the United States’ Orphan Drug Act (ODA) as a model for subsequent policies in other regions and countries. It starts with a historical overview of the creation of the term “rare diseases”, continues with a summary of the evidence available on the US ODA’s positive and negative impacts, and provides a summary of the different proposals to reform these incentives in light of the negative outcomes described. Finally, it describes some key aspects of the Japanese and European policies, as well as some of the challenges captured in the literature related to their impact in Low- and Middle-Income Countries (LMICs).

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“…4 Orphan drugs may also use expedited programs during their development or FDA review, should they qualify. 5 Previous literature has examined trends in overall use of expedited programs. [6][7][8][9] However, to our knowledge, no publication has comprehensively evaluated how the FDA and applicants use these programs in combination (ie, "stacked").…”

Section: Introductionmentioning

confidence: 99%

“… 4 Orphan drugs may also use expedited programs during their development or FDA review, should they qualify. 5 …”

Section: Introductionmentioning

confidence: 99%

“… 6 , 7 , 8 , 9 However, to our knowledge, no publication has comprehensively evaluated how the FDA and applicants use these programs in combination (ie, “stacked”). Similarly, while other research has examined the trends in orphan drug approvals for both biologics and small-molecule drugs, 5 , 10 , 11 , 12 published data on how orphan vs nonorphan drugs use the 4 expedited programs are sparse. In this study, we examined use of the programs alone or in combination to approve novel biologics and small-molecule drugs by specific drug indication and orphan drug designation status from 2008 to 2021.…”

Section: Introductionmentioning

confidence: 99%

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Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021

2022

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ImportanceThe US Food and Drug Administration (FDA) has 4 programs that can be used alone or in combination to expedite drug availability: Accelerated Approval, Breakthrough Therapy, Fast Track, and Priority Review. Drugs using these programs can include novel drugs, which do not contain a previously FDA-approved active moiety, and orphan drugs, intended for diseases or conditions affecting fewer than 200 000 people; to date, no comprehensive evaluation of how these programs have been used in combination has been published.ObjectiveTo assess how often and in what combinations expedited programs are used in the development and review of approved novel biologics and small-molecule drugs, stratified by orphan drug status and indication.Design, Setting, and ParticipantsThis cross-sectional study evaluated all novel drugs that were FDA approved between January 1, 2008, and December 31, 2021.Main Outcomes and MeasuresThe main outcome was the frequency with which expedited programs were used and in what combinations, stratified by orphan drug status and drug type (small molecule vs therapeutic biologic). The unit of analysis was the novel drug–indication pair because a drug can be approved for multiple indications, each of which may use a different expedited program or differ in orphan drug status.ResultsThe study included 581 novel drug–indication pairs approved during the 14-year study period; 252 (43.4%) were orphan drugs, 139 (23.9%) were therapeutic biologics, and 442 (76.1%) were small-molecule drugs. Use of at least 1 expedited program increased from 11 of 26 drug-indication pairs (42.3%) in 2008 to 41 of 55 (74.5%) in 2021. Of the 363 approved drug-indication pairs using at least 1 expedited program, 225 (62.0%) were orphan drugs; at least 1 expedited program was used by 97 of the 139 approved biologic drugs (69.8%) and by 266 of the 442 approved small-molecule drugs (60.2%). Eighty-two of the 581 novel drug–indication pairs (14.1%) used the Accelerated Approval Program; of those, 65 (79.3%) were oncology drugs and 70 (85.4%) had an orphan designation.Conclusions and RelevanceThe study showed that use of the FDA’s expedited programs to bring novel drugs to market in the US increased from 2008 to 2021. The findings suggest that this trend is likely to continue.

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Drugs and biologics receiving FDA orphan drug designation: an analysis of the most frequently designated products and their repositioning strategies

Cited by 11 publications

References 23 publications

Successfully Navigating Food and Drug Administration Orphan Drug and Rare Pediatric Disease Designations for AAV9-hPCCA Gene Therapy: The National Institutes of Health Platform Vector Gene Therapy Experience

Successfully Navigating Food and Drug Administration Orphan Drug and Rare Pediatric Disease Designations for AAV9-hPCCA Gene Therapy: The National Institutes of Health Platform Vector Gene Therapy Experience

Pharmaceutical policy and innovation for rare diseases: A narrative review

Use of US Food and Drug Administration Expedited Drug Development and Review Programs by Orphan and Nonorphan Novel Drugs Approved From 2008 to 2021

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