Orphan Drug Development – PharmaTimes

Rare diseases (RD) or orphan diseases, by definition, are conditions that affect a small number of individuals. The exact number of RDs is unknown, but it is estimated to be around 6000-8000.


Although each individual disease is rare, their collective prevalence is estimated at approximately 6-8% of the population. This implies that more than 450 million people worldwide could have DR. Moreover, although heterogeneous in their causes and manifestations, most RDs are chronic and debilitating and are an important cause of disability and early death. They manifest as birth defects, intellectual disabilities, and many other serious signs and symptoms. Most lack curative therapies. They are a significant cause of health expenditure for individuals and society and also have an indirect economic impact due to lost productivity. For these reasons, DRs constitute a relevant and global public health problem.

FDA support for orphan drug development programs

Supporting the development and evaluation of new treatments for rare diseases is a key priority for the FDA. The FDA has the authority to grant orphan drug designation to a drug or biologic to prevent, diagnose, or treat a rare disease or condition. Orphan drug designation qualifies sponsors for incentives including: tax credits for qualified clinical trials, waiver of user fees, potential for market exclusivity for 7 years after approval

Challenges of orphan drug development

The development of orphan drugs presents several major challenges and obstacles, such as low disease prevalence, disease severity, small and heterogeneous patient populations, difficulties in patient recruitment, and limited knowledge of natural history. disease, among others. Rare diseases that affect limited patient populations and have not been extensively studied can pose significant research and development challenges for companies seeking to identify new drugs to treat them. In a recent survey by the Tufts Center for the Study of Drug Development, rare drug developers reported that they face many kinds of challenges due to lack of knowledge about disease mechanisms. In addition to an incomplete understanding of the biology underlying these diseases, researchers often lack information about their natural history and do not know how to translate the information gathered into knowledge useful for drug development. In addition, they may have to choose between several potential disease pathways and establish endpoints and outcome measures.

Orphan drug development strategies

Several strategies can be used to plan and overcome these clinical and regulatory challenges, namely better clinical trial design, better patient recruitment, and closer collaboration with regulatory authorities and patient associations.

In orphan drug development, efficient study designs with appropriate comparators are essential to generate interpretable clinical data for approval. However, designing effective clinical trials with clinically meaningful endpoints requires close collaboration between statisticians, clinicians, and other clinical trial professionals, as well as careful attention to patient needs.

Regulatory approvals

A drug for a rare disease may be approved on the basis of a single appropriately controlled trial, provided the trial provides sufficient evidence and safety information to allow a benefit/risk assessment. In some cases, the FDA even accepts non-traditional treatment efficacy data.

Manohara Halasiddappa

Chief of Clinical Operations, San Francisco

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