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Orphan Drugs: Product Similarity & Market Exclusivity
15-08-2018

#Orphan Drugs: Product Similarity & Market Exclusivity

The effects of the EU orphan legislation are substantial: over 1,950 orphan designations have been issued by the European Commission since the year 2000, of which 142 have resulted in authorised medicinal products so far (EMA Annual report 2017). The EU orphan incentives stimulate the development of medicinal products to make sure patients suffering from rare diseases have access to the same quality of treatment as other patients. For many start-ups and small pharmaceutical companies, developing a drug without the benefits of the orphan incentives is unthinkable and the orphan drug designation (ODD) is an absolute condition for investments.  

However, with more and more drugs getting approved while maintaining the designated orphan status, developers of drugs within the same orphan drug condition see themselves faced with a higher raised bar. Questions like “what are the options for a product to enter the market in case of an already approved drug for the same therapeutic indication” are frequently asked? The situation is complex as two different set of criteria of the orphan drug regulation apply, each with its own conditions and consequences:

  1. Market exclusivity of the competitor
  2. Maintaining the orphan drug designation status by showing significant benefit.

The criteria and options for entering the market in case of another orphan drug approved for the same therapeutic indication with market exclusivity period are summarized in the scheme below:

MA: Marketing Authorisation; ODD: Orphan Drug Designation

*Similar being defined as an identical active substance, or an active substance with the same principal molecular structural features (but not necessarily all of the same molecular structural features) and which acts via the same mechanism (EC 847/2000 Art 3.3(c), amended by EC 2018/781).

**Clinical superiority being defined as a medicinal product is shown to provide a significant therapeutic or diagnostic advantage over and above that provided by an authorised orphan medicinal product (EC 847/2000, Art 3.3(d)).

***Significant benefit means a clinically relevant advantage or a major contribution to patient care (EC 847/2000, Art 3.2)

 


1. SIMILAR PRODUCTS: MARKET EXCLUSIVITY

The first criterium in getting your product registered relates to the presence of a 10-year market exclusivity for another designated orphan drug being granted a marketing authorisation. I.e. another similar medicinal product can in principle not be placed on the market in the EU for the same therapeutic indication (Art 8(1) EC 141/2000). In this concept, a similar medicinal product is defined as an identical active substance, or an active substance with the same principal molecular structural features (but not necessarily all of the same molecular structural features) and which acts via the same mechanism (for detailed explanation, refer to EC 847/2000 Art 3.3(c), C(2008)4077, and EC 2018/781). The market exclusivity period can be extended by two additional years when the results of studies in the paediatric population are presented in accordance with a Paediatric Investigation Plan. The market exclusivity incentive prevents other companies to easily place a generic product on the market, irrespective of the legal basis of the original application and of the patent situation.

Marketing authorisation for similar products

If the active substance is indeed similar, your product can only be placed on the market for the same therapeutic indication when

  1. consent of the original marketing authorisation holder is obtained,
  2. the original marketing authorisation holder is unable to supply sufficient quantities or
  3. the medicinal product is safer, more effective or otherwise clinically superior despite having a similar active substance (for a detailed explanation see: C(2008)4077).

In these cases, marketing authorisation will be granted and the product can be launched but without the orphan drug status and the rights of market exclusivity.

If the situation and clinical program of your similar product allow, the planned indication might be adjusted to target a patient group not protected by the market exclusivity. Alternative indications might already be explored during the development of your product in case of the expected competition of a similar product. The adapted indication can but might not necessarily have an orphan drug status.

Marketing authorisation for non-similar products

If your product contains a non-similar active substance while the intended indication is similar, marketing authorisation can be granted by the EMA or national authorities without further provisions or restrictions related to marketing exclusivity of the registered competitive product. The usual positive benefit/risk requirement for your product applies for a marketing authorisation without ODD status and without benefits from incentives related to ODD status. In case the marketing authorisation of your product is granted via a full or full-mixed application, i.e. based on own clinical studies, the usual data exclusivity (8 years) and market protection periods for this type of application apply, protecting you from generic products for the same indication entering the market. Also, the patent protection period applies as usual.


2. MAINTAINING ODD AFTER MA FOR NON-SIMILAR PRODUCTS: SIGNIFICANT BENEFIT

In case ODD status is wished additional to the marketing authorisation, for either the protection period of market exclusivity or to increase market value, the second criterium of significant benefit has to be complied with. To maintain ODD status after marketing authorisation of your product, clinically relevant advantage or major contribution to patient care, compared to all authorised orphan drug product and other products and treatments for that orphan condition needs to be demonstrated.

This concept of significant benefit can be based on improved efficacy, improved safety or a major contribution to patient care and there has to be a high probability for patients to actually experience this benefit when using your product. At the time of marketing authorisation application, the demonstration has to be based on clinical comparison data. Depending on the situation either a direct or an indirect comparison between your product and the competitive product(s) can be made. Likewise, comparison with other treatments which the patients diagnosed with the orphan disease may receive needs to be provided. If benefits to patients are expected to be similar or if the investments to gather comparison data via clinical studies will be too high or time-consuming, your product can still obtain a marketing authorisation without the ODD status as explained above in this blog.

The concept and requirements for the significant benefit are further explained in Recommendations from the Committee for Orphan Medicinal Products (EMA/COMP/15893/2009), Guideline on the format and content of applications for designation as orphan medicinal products (ENTR/6283/00) and Commission notice 2016/C 424/03.


3. WHAT STEPS CAN YOU TAKE?

The approval of a competitor orphan drug product with rights of market exclusivity in the target indication of your product will raise the bar, but options still remain to register and market your product. If not similar in active substance, market authorisation with and without maintaining ODD status is possible. If you have an EU orphan drug status for your product, this is what you can do:

  • Continuously follow-up on programs of competitor products, similar or non-similar, in the orphan drug condition not to be surprised by granting of approval of another orphan drug in your target indication.
  • Even though competitor products have not been granted marketing authorisation, evaluate similarity and significant benefit criteria explained in this blog and the pros and cons for each option.
  • Anticipate if you need to prepare for alternative routes in your development program.
  • In case extra investments in the clinical program are needed to maintain the ODD status at the time of marketing authorisation, assess whether the investments balance the expected profits on the market.

4. RECOMMENDED READING

 

Blog by: Patricia Baede, Liesbeth Hof


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