US Orphan Drug Designation for Rare Diseases

Obtaining orphan drug designation from the FDA opens access to important incentives that can facilitate and encourage the research and development of treatments for rare diseases. However, navigating the designation process requires thorough planning and preparation. By understanding and effectively navigating this process, sponsors can contribute significantly to addressing unmet medical needs for these underserved patient communities.

Orphan drug designation is a special status granted by the FDA to drugs and biologics intended to treat rare diseases or conditions. Officially defined as those affecting fewer than 200,000 persons in the United States, these conditions are also referred to as ‘orphan’ indications due to the lack of commercially viable treatments available.

To qualify for orphan designation, a candidate product must meet three criteria established by the Orphan Drug Act:

1. It must be intended to treat, diagnose, or prevent a rare disease or condition.
2. A sponsor can request orphan-drug designation for a new, unapproved drug or a new use for an existing, marketed drug. Additionally, a sponsor of a drug that is otherwise the same drug as an already approved drug can seek the same designation if they can suggest their drug may be clinically superior.
3. The sponsor must provide a scientific rationale and supporting data, such as preliminary clinical or preclinical research findings, to demonstrate a reasonable likelihood that the product will be effective for the intended rare disease indication. While formal clinical trial data is not required at this stage, the FDA assesses whether there is a sound biological or pharmacological basis for the product.

To formally apply for orphan designation, sponsors must submit a written request to the Office of Orphan Products Development (OOPD) at the FDA. This request serves to notify the agency of the sponsor’s intent to pursue orphan status and develop an orphan product.

For a drug to be considered for orphan-drug designation, it must be intended for the treatment of a rare disease or condition. The sponsor should provide information about the disease, the proposed use of the drug, and why it is needed. They should also describe the drug itself, including its active ingredients and physical properties, as well as any relevant data from laboratory, animal, and clinical studies. The data provided should establish a plausible basis for the drug's use in treating the rare disease or condition. This includes any positive, negative, or inconclusive results. Unpublished and published research papers related to the drug's use should also be submitted.

If the FDA approves the designation request, it qualifies sponsors for a suite of valuable incentives intended to make developing an orphan product economically viable. These include:

• 7 years of U.S. marketing exclusivity upon FDA approval to prevent competing products.
• 50% tax credit on clinical trial costs incurred after designation is granted.
• Waiver of new drug application user fees, which can total hundreds of thousands of dollars.
• FDA assistance throughout the development and review process
• Eligibility for federal grants from the Orphan Products Grants Program

Together, these benefits aim to offset some of the financial risks associated with developing treatments for diseases that impact only a small number of patients.

Navigating the orphan drug designation process successfully requires diligent planning and preparation from sponsors. A strong designation application that fully addresses all required elements and provides relevant scientific data is important. Early FDA consultation is also recommended. If approved, designation unlocks substantial benefits critical to making rare disease drug development financially feasible. Strategically managing the application demonstrates commitment to FDA standards needed to ultimately deliver therapies. Doing so represents an important first step for sponsors aiming to address significant unmet needs in orphan diseases.