Dose‐Finding Studies Among Orphan Drugs Approved in the EU: A Retrospective Analysis

Schuller, Y.; Wied, Christine Gispen-de; Hollak, Carla E. M.; Leufkens, H.G.M.; Stoyanova-Beninska, Violeta

doi:10.1002/jcph.1304

Cited by 3 publications

(2 citation statements)

References 51 publications

(79 reference statements)

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“…In the European Union (EU), RDs have been defined as those occurring in less than 1 per 2000 people [ 3 ]. Like the US orphan drug laws, attention to orphan diseases and pharmaceuticals exists in the EU and Japan [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Psychosocial Considerations for the Child with Rare Disease: A Review with Recommendations and Calls to Action

et al. 2022

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Rare diseases (RD) affect children, adolescents, and their families infrequently, but with a significant impact. The diagnostic odyssey undertaken as part of having a child with RD is immense and carries with it practical, emotional, relational, and contextual issues that are not well understood. Children with RD often have chronic and complex medical conditions requiring a complicated milieu of care by numerous clinical caregivers. They may feel isolated and may feel stigmas in settings of education, employment, and the workplace, or a lack a social support or understanding. Some parents report facing similar loneliness amidst a veritable medicalization of their homes and family lives. We searched the literature on psychosocial considerations for children with rare diseases in PubMed and Google Scholar in English until 15 April 2022, excluding publications unavailable in full text. The results examine RD and their psychosocial ramifications for children, families, and the healthcare system. The domains of the home, school, community, and medical care are addressed, as are the implications of RD management as children transition to adulthood. Matters of relevant healthcare, public policies, and more sophisticated translational research that addresses the intersectionality of identities among RD are proposed. Recommendations for interventions and supportive care in the aforementioned domains are provided while emphasizing calls to action for families, clinicians, investigators, and advocacy agents as we work toward establishing evidence-based care for children with RD.

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Section: Introductionmentioning

confidence: 99%

Psychosocial Considerations for the Child with Rare Disease: A Review with Recommendations and Calls to Action

et al. 2022

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“…The information from such studies is then used to inform the dosing strategy for larger safety and efficacy trials, as well as dosage adjustments for specific populations based on intrinsic and extrinsic factors. However, given the limited number of patients available for clinical studies within a rare genetic disease patient population, adequate dose-finding studies are challenging to conduct and may not be performed consistently in these drug development programs [ 11 , 12 ]. Understanding both the challenges associated with conducting dose-finding studies in rare disease populations and the importance of dose selection and optimization for successful drug development, we sought to characterize the dose-finding studies and analyses conducted for recently approved drugs to provide insight on current practices for dose-finding in rare genetic disease drug development.…”

Section: Introductionmentioning

confidence: 99%

Dose-finding studies in drug development for rare genetic diseases

Wang

Feng

et al. 2022

Orphanet J Rare Dis

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Background The small patient populations inherent to rare genetic diseases present many challenges to the traditional drug development paradigm. One major challenge is generating sufficient data in early phase studies to inform dose selection for later phase studies and dose optimization for clinical use of the drug. However, optimizing the benefit-risk profile of drugs through appropriate dose selection during drug development is critical for all drugs, including those being developed to treat rare diseases. Recognizing the challenges of conducting dose finding studies in rare disease populations and the importance of dose selection and optimization for successful drug development, we assessed the dose-finding studies and analyses conducted for drugs recently approved for rare genetic diseases. Results Of the 40 marketing applications for new molecular entity (NME) drugs and biologics approved by the United States Food and Drug Administration for rare genetic diseases from 2015 to 2020, 21 (53%) of the development programs conducted at least one dedicated dose-finding study. In addition, the majority of drug development programs conducted clinical studies in healthy subjects and included population pharmacokinetic and exposure–response analyses; some programs also conducted clinical studies in patient populations other than the disease for which the drug was initially approved. The majority of primary endpoints utilized in dedicated dose-finding studies were biomarkers, and the primary endpoint of the safety and efficacy study matched the primary endpoint used in the dose finding study in 9 of 13 (69%) drug development programs where primary study endpoints were assessed. Conclusions Our study showed that NME drug development programs for rare genetic diseases utilize multiple data sources for dosing information, including studies in healthy subjects, population pharmacokinetic analyses, and exposure–response analyses. In addition, our results indicate that biomarkers play a key role in dose-finding studies for rare genetic disease drug development programs. Our findings highlight the need to develop study designs and methods to allow adequate dose-finding efforts within rare disease drug development programs that help overcome the challenges presented by low patient prevalence and other factors. Furthermore, the frequent reliance on biomarkers as endpoints for dose-finding studies underscores the importance of biomarker development in rare diseases.

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Challenges, approaches and enablers: effectively triangulating towards dose selection in pediatric rare diseases

Durairaj¹,

Bhattacharya²

2023

J Pharmacokinet Pharmacodyn

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Dose‐Finding Studies Among Orphan Drugs Approved in the EU: A Retrospective Analysis

Cited by 3 publications

References 51 publications

Psychosocial Considerations for the Child with Rare Disease: A Review with Recommendations and Calls to Action

Psychosocial Considerations for the Child with Rare Disease: A Review with Recommendations and Calls to Action

Dose-finding studies in drug development for rare genetic diseases

Challenges, approaches and enablers: effectively triangulating towards dose selection in pediatric rare diseases

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