What do you think have diseases like Huntington´s disease, Fabry disease, Amyotrophic lateral sclerosis, Fragile X syndrome and cystic fibrosis in common? They belong to rare diseases, diseases that affect no more than 5 people out of 10 000 in EU which means that about 250 000 people maximally are affected by a single disease. However, in most cases there is 1 person in 100 000 affected by a disease. It is therefore not so hard to imagine that this number of patients is not so attractive for drug developers since they reasonably expect that they cannot get returned their investment into a drug development by selling such medicine on this small market.

Just to imagine how many people together are affected by rare diseases- a few numbers from the European Medicine Agency (EMA) webpage: There exist 5000 to 8000 distinct rare diseases, affecting between 27 mil and 36 mil people in EU. Most of the rare diseases are caused by a genetic origin and rest is accounted to degenerative and proliferative causes.

Taken in account that there are a few medicines available and there is a lack of any scientific information about most of the rare diseases, we can see an urgent unmet medical need here and millions of people left without any hope.

Despite predominantly governments are in duty to take care of public health and act in public interest and to provide help also to people with rare diseases, we see numerous initiatives supporting development of orphan drugs funded above all by non-governmental bodies.

On the European level, the European commission via the EMA supports similarly to the Food and Drug administration (FDA), orphan drugs development. In case of the EMA regulatory body, an orphan drug must meet certain criteria:

• it must be intended for the treatment, prevention or diagnosis of a disease that is life-threatening or chronically debilitating;
• the prevalence of the condition in the EU must not be more than 5 in 10,000 or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development;
• no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorised, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition.

This is quite straightforward definition. Such medicine can then benefit from certain incentives such as protection from competition once on the market (for 10 years) or protocol assistance. There are further incentives for SMEs like reduced fees and administrative and procedural assistance from EMA.

As we will discuss next, in frame of the Horizon 2020, an EU funding program for scientific projects, there have been calls running and in preparation to support development of orphan drugs.

In the past, there have been already some calls within the Horizon 2020 which fully or partly touched rare diseases like PHC-14-2015, FPA-01-2014, SC1-PM-12-2016 or INFRAIA-1-2014-2015. For the open calls, we can mention the NMBP-10-2016 call (Nanoformulation of biologicals) ending in May 2016 and ERN-01-2016 (ERN-2016 – European Reference Networks – Framework Partnership Agreement) with deadline in June 2016 which are partly focused also on rare diseases.

Two forthcoming calls are the most relevant and specifically focused on rare diseases.

The SC1-PM-03-2017 call (Diagnostic characterisation of rare diseases) will be open in July, 29^th, 2016 and closed in April, 11^th, 2017. Aim of this call is to apply genomics and other –omics or high–throughput approaches for molecular characterization of rare diseases. This is thought to be a large-scale proposal with an expected EU contribution at around 15 mil EUR. The selected proposal shall contribute to the objectives of, and follow the guidelines and policies of the International Rare Diseases Research Consortium IRDiRC (www.irdirc.org).

The second call SC1-PM-08-2017 (New therapies for rare diseases ) is fully dedicated to clinical development of orphan drugs, it is planned to be open in July 2016 and a deadline for the 1^st stage is planned to be in October 2016 and for the 2^nd stage in April 2017.

There are certain prerequisites to be fulfilled to apply for this call:

1) Orphan designation has been given by the European Commission (via EMA),

2) The proposed clinical trial design takes into account recommendations from protocol assistance given by EMA (The protocol assistance from EMA which is a kind of scientific advice attracts fees. For more details see the EMA web page), and

3) A clear patient recruitment strategy is presented.

Again here, the proposals should follow the guidelines and policies of IRDiRC.

According to the SC1-PM-08-2017 topic description, “the intervention must have been granted the EU orphan designation at the latest on the date of the full proposal call closure”. The whole procedure for orphan drug designation at EMA takes in full about 11,5 months from date of filing (it is also recommended to have free pre-submission meetings with the EMA Orphan Medicines Office and EMA Scientific Advice Office). So, if a drug developer does not have yet an orphan drug designation for a drug to be a part of the SC-1-PM-08-2017 call, it has to be applied at latest in next few days to keep Horizon 2020 timelines. Otherwise this call will be applicable only to drug developers having already the orphan drug designation or being already in process of getting it.

Though drug developers have not had in the past so much interest in orphan drug development, situation is changing due to more factors. An increasing support from EU, governments and non-governmental organizations is one reason. A second factor is that companies can use the orphan drug  as a “lift” for other drugs, e.g targeting the same molecule. Orphan drugs will take advantages of its designation to get incentives and to be on market quicker than a usual drug and to get longer protection and the second-use drug can profit from that. At last, involvement in development of a drug for people left without any hope and even knowing that the direct return of investment will be low or none, can improve public image of pharmaceutical industry and companies involved. None of these reasons is bad and if at the end they improve understanding of rare diseases and can help millions of people, this is something which counts and matters.

Picture used at this post ©https://ec.europa.eu/programmes/horizon2020/