Access to Orphan Drugs in Turkey

Gülce Belgin and Donald Macarthur explore the options available for companies to meet the needs of the rare disease population in Turkey.

Though Turkey remains outside the European Union and pharmaceutical cost containment features strongly, patients had access with reimbursement to 73% (62 of 85) of orphan drugs approved in the EU in 2015, a higher proportion than in some EU member states. Just 27% (23) of these available drugs were subject to Turkish marketing authorizations, however.

Straddling two continents, Turkey is home to an estimated five million rare disease patients¹. Consanguinity or marriage between close family members has a prevalence of 17% in western regions of the country, such as Ankara, Istanbul and Izmir, but reaches 35% further east². The result is that many offspring are at greater risk of certain genetic disorders and, with 80% of rare diseases known to have a genetic origin, the implications are clear³.

Unlike the EU and several individual countries, specific legislation to promote the development and commercialization of orphan drugs is still at the draft stage. The Ministry of Health defines such products for use ‘in clearly described diseases that are seen in a frequency of less than 1/100,000’, a prevalence ceiling sometimes described elsewhere as ultra-rare.

There are three channels available to obtain unapproved products, according to the Ministry’s latest (2014) Guidelines on the Importation of Medicines and Their Use:

(1) Off-label use of drugs approved in Turkey

Application needs to be made to the Turkish Medicines and Medical Devices Agency if the proposed treatment is ‘off-label’, i.e. approved for another indication, at a different dose, or for use in a different age range of patient.

(2) Named-patient imports

Personal importation can be allowed under the responsibility of the patient’s physician for products approved in another major jurisdiction and either unapproved in Turkey or approved but not present in the local market despite real medical need. The Medicines and Medical Devices Agency again grants permission on a case-by-case basis. Actual importation, direct from the manufacturer or with a documented chain of custody, and distribution in Turkey are primarily undertaken by the Turkish Pharmacists’ Association. The Turkish Competition Authority is investigating whether this amounts to an abusive monopoly. 

(3) Compassionate use Program

Patients with life-threatening or other serious diseases that are not adequately treated by a product approved in Turkey may receive a potentially-useful import providing they are ineligible for any clinical trial of the drug in Turkey. Products which have completed Phase 2 and started Phase 3 trials overseas are in principle accepted in this program.

Advantages of named-patient imports

Manufacturers are required to provide stock free-of-charge for compassionate use programs. Named-patient imports, however, are generally supported by reimbursement at prices which are exempt from international reference pricing and mandatory discounts. Another advantage to the company, compared to the normal market access route, is that the prevailing euro/Turkish lira exchange rate is applied, not an historical one. All orphan drugs are also exempted from pharmacoeconomic demands.

Several orphan drug companies have employed the named-patient channel, sometimes over prolonged periods. Pharmaceutical imports have unsurprisingly risen 13% by value over the past five years. This is not something the government welcomes, especially when there is a total budget deficit and the pharmaceutical industry represents the third-largest contributor to the trade deficit after defence and energy supplies. The reimbursement authority, the Social Security Institution, is now is trying to introduce ‘alternative reimbursement models’ to negotiate and decrease the cost burden through special agreements. This development is at an early stage and, while it is difficult to predict the exact outcome, it is clear companies will need reasoned justification to take the named-patient approach in future. 

Regular channel

Supporting the sale with a marketing authorization remains important in making orphan drugs available to those who need them of course. This is the most reliable and fastest way, not only for patients and prescribers, but also for pharmaceutical companies, health administrators and the reimbursement authority.

It should be added that Turkey is a country with many advantages for clinical trials, a further route to patient access. At around 76 million, the overall population while young but ageing is larger than almost all other European nations, and physicians and medical facilities are of high quality. In 2012 alone, 23 applications were made for clinical studies on orphan drugs. By broad therapeutic area these could be broken down as oncology-hematology (12 trials), genetic disorders (4), ophthalmological diseases (2) and others (5)³. Development of national databases are planned for prevention, surveillance, diagnosis and treatment of rare diseases. Orphanet-Turkey also contributes to increasing general awareness of rare diseases and orphan drugs.

Gülce Belgin (gulce.belgin@proceutica.com.tr) is Managing Director and Donald Macarthur is Adviser at Proceutica, an independent regulatory, market access and life cycle management consultancy and service provider.

References

• DUNDAR M. et al. Turkiye’de Nadir Hastaliklar ve Yetim Ä°laclar: Medikal ve Sosyal Problemler, Erciyes Medical Journal 2010; 32(3): 195-200    

• Türkiye Aile Sağlığı Planlama Vakfı, Görünüm Dergisi Ocak 2011, sayfa 2

• ILBARS H, IRMAK DK, AKAN H. Orphan Drugs: R&D Challenges with Updates from Turkey and Middle East Countries Journal for Clinical Studies, 2014; 6(2):58-63