The European Medicines Agency (EMA) is looking help sponsors developing new orphan drugs by clearing up questions on how they can demonstrate their product's improvement over existing therapies.

To do so, the agency will be hosting a workshop on 7 December 2015, where it says industry, regulators, health technology assessment (HTA) bodies and other groups will have the opportunity to discuss approaches to demonstrating "significant benefit" for orphan products.

Orphan Designation in the EU

Orphan product designation was first introduced in the EU in 2000 under Regulation (EC) No 141/2000. The regulation established the procedure for orphan product designation, detailed incentives for orphan products and formed the Committee for Orphan Medicinal Products (COMP) which is charged with reviewing applications for orphan designation.

In the EU, orphan products are given a period of 10 years market exclusivity for a given indication. Sponsors of orphan products also qualify for scientific advice and protocol assistance from EMA, and may qualify for fee reductions depending on their status as a micro-, small- or medium-sized enterprise (SME).

To receive orphan designation, a product must satisfy several conditions:

• The medicine must treat, prevent or diagnose a life-threatening or chronically debilitating condition.
• The condition must affect fewer than 5 in 10,000 people in the EU. Alternatively, if a condition affects more than 5 in 10,000 people in the EU it may still be considered for orphan designation if it is "unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development."
• Finally, for a treatment to qualify for orphan designation there must be no existing approved treatments for the indicated condition, or if there are, the product in question must offer significant benefit over existing treatments.

Demonstrating Significant Benefit

When there are already existing treatments for a rare disease, a company must demonstrate a "clinically relevant advantage or a major contribution to patients." This is done to limit the orphan product incentives to products that can provide a significant gain over existing options.

In hosting the workshop, EMA says it hopes to provide clarification for drug sponsors on the "approach that should be followed … to demonstrate significant benefit of an orphan medicine over existing treatments."

As more orphan products are authorized, the agency says it has become more difficult to demonstrate significant benefit for products in the same therapeutic area. The agency says it intends for the December workshop to clarify "the concept of significant benefit as well as the methodology and type of evidence required to support it."

The agency says it will also consider the "views, interests and concerns of the various stakeholder groups" to draft future guidance on orphan products.

EMA