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Rare and Orphan Drug Development in the EU

A pharmaceutical company is granted orphan designation for a medicine that treats Hunter Syndrome. The company goes on to receive marketing approval for the medicine.

The approved medicine is administered through intravenous infusion. This route of administration, while effective for some, does not address the needs of patients with the most severe form of Hunter Syndrome. For these patients, associated cognitive disorders are not treated through IV infusion because the medicine does not cross the blood-brain barrier.

With this in mind, the pharmaceutical company sets out to develop a medicine with the same active substance, delivered intrathecally.

Should the second, enhanced medicine be eligible to receive orphan designation and subsequent incentives?

Only July 29, the EU’s highest court upheld a March 2018 ruling by the General Court on case T-80/16 Shire Pharmaceuticals Ireland v EMA, upon which the scenario above is based. In short, the court sided with the pharmaceutical company, finding that the second medicine was eligible for its own orphan drug designation because it differed from the first in composition, method of administration and therapeutic effects.

So what does this decision mean for European orphan drug development? And how is it the same or different in the US?

Distinction between active ingredient and drug product

The Shire v EMA case centers around an important distinction: two products that contain the same active ingredient (EU: substance) aren’t necessarily the same Drug Product (in the EU, this is called Medicinal Product). Shire was able to show the two medicinal products which contained the same drug substance were distinct in composition, method of administration and therapeutic effect. In both the EU and US, a sponsor may apply for orphan designation for a product containing the same active substance as a previously approved product for the same indication as long as they can show that the product provides a “significant benefit” (or in the US, that the product is “clinically superior”) over other available products.

EU and US orphan drug designation requirements

While the process and criteria for orphan drug designation in the EU and US is similar in many ways, there are several key differences.

In the EU, medical plausibility goes one step beyond scientific rationale requiring demonstration that the condition is life-threatening or seriously debilitating. EU regulations also require evidence in all applications that either no satisfactory method of diagnosis, prevention or treatment currently exists or that the new product will be of significant benefit over the existing method.

Comparison of key criteria for orphan designation in the EU and US

– Medical plausibility
– Prevalence
– Significant benefit
– Scientific rationale
– Prevalence

Implications for rare and orphan drug development

In 2014, a US court case with similar questions surrounding the interpretation of rare and orphan legislation and how it applies to enhanced medicines opened new doors for sponsors seeking approval of enhanced rare and orphan drugs in the US. We anticipate that the court’s decision in Shire v EMA will have similar implications for rare and orphan drug development in the EU.

Premier Consulting has supported development programs in the US and EU, helping sponsors navigate regulatory criteria to achieve orphan designation and secure marketing exclusivity. To discuss how Premier Consulting can support your program, contact us.