Developing drugs for rare diseases poses a range of clinical, regulatory and commercial challenges. The small number of patient populations are difficult to identify and recruit for clinical trials. Many orphan diseases are genetic. Often these patients have complex phenotypes that react very differently to proposed treatment protocols. The diseases may be poorly understood, making setting clinical endpoints, biomarkers or outcome measures difficult. Patients may include sensitive subpopulations, ranging from neonates and pediatrics to people with co-morbidities, where conducting clinical trials is ethically problematic.
Modeling and simulation (M&S) approaches are not only ideal for the development of orphan drugs, but are encouraged by regulators. M&S allow quantifying the drug-disease-trial and exposure-response models from small populations, gaining insight into biomarkers and endpoints. It facilitates dose selection, identifying drug-drug and drug-food interactions, recommending the pediatric treatment when only adult data is available, and modeling the impact of the drug on other disease states.
Early and careful planning is critical for rare disease development, and Certara’s hundreds of PhD quantitative and regulatory scientists provide expert guidance and active support from pre-IND meetings through clinical development and post-market approval.
We have supported the approval of scores of orphan drugs, including over 90% of new novel drug approvals with orphan designation in the past 6 years by the US FDA with our software or services. As the global leader in model-informed drug development, we have worked on more rare and orphan drug development programs than any other consultancy.
Our expertise in clinical pharmacology strategy and modeling and simulation (M&S) services enable us to quantify drug-disease-trial and exposure-response models from small orphan patient populations providing insights into biomarkers and endpoints.
Using quantitative approaches, Certara informs trial design, dose selection and dosing regimen, identifying drug-drug and drug-food interactions along with other safety factors to optimize conditions for orphan drug use. We can also model the impact of an orphan drug in development on other disease states or untested populations.
These proven quantitative methods are actively encouraged by global regulators who have demonstrated flexibility in approving orphan drugs either through an accelerated approval pathway, the elimination of a second pivotal clinical trial, or applying modeling and simulation in lieu of certain trials.
Increased pricing pressure and competition for orphan drugs have impacted how payers and HTAs evaluate these new therapies. The sponsor’s burden to demonstrate value not only for competitive products but also for products with no therapeutic alternatives has been impacted by the doubling of new rare disease approvals, high prices, restricted access and overall budgetary impact.
Certara develops a quantitative, multi-criteria, decision analysis framework adapted to the specific issues in rare disease development and access, including:
- Quality of evidence
- Disease severity
- Ethical considerations
- Population-level factors
- Economic impact of the disease
- Specific budgetary impact.
By combining disease information, patient input, real world data, and innovative pricing and contracting strategies with the wider social and health benefits, we build robust, evidence-based results to justify market access and pricing.
As seasoned drug developers, Certara’s team of scientists, clinical pharmacologists, regulatory strategists and regulatory writers work alongside orphan drug development teams on global drug approvals. Our regulatory team team has more than 200 experts and writers with proficiency in orphan global filings, as well as a deep understanding of how to articulate the results derived from modeling and simulation.
Certara has supported the approval of scores of orphan drugs using our pharmacometric portfolio of solutions, including physiologically-based pharmacokinetics (PBPK) and population PK (popPK), including:
- Genetic and hereditary
- Central nervous system (CNS)
- Bone and muscle disease
- Anti-infectives and antivirals
- Blood disorders