Interview | For patients with rare diseases timely delivery is crucial

Yanko Popstoilov is the Manager of Reimex Pharma Ltd. The company specialises in the supply of medicinal products for the treatment of rare diseases. It is built on the principles of the international and national best practices in the industry.

Popstoilov holds a Master's degree in Healthcare Management. He is a founder and member of the Management Board of the Association of Importers of Unauthorised Medicinal Products for the Treatment of Rare Diseases.

Mr Popstoilov, the science of rare diseases has never advanced as rapidly as it does today. Why, then, does access to treatment around the world remain so difficult?

The development of science is outpacing access. More than 300 million people worldwide live with a rare disease. These diseases number in the thousands, yet an approved treatment exists for only about 5% of them. At the same time, therapies are emerging that only a decade or so ago seemed like science fiction - by the end of 2025, the U.S. Food and Drug Administration (FDA) had already approved 26 gene therapies.

These medicines, however, are manufactured in small quantities, often by a single manufacturer worldwide, and they are expensive, because the costs of their development are spread across a small number of patients. That is why the decision on where and when to place them on the market is, above all, an economic one. The large, solvent markets come first. The small ones are often last - if their turn comes at all.

Alongside the economic considerations, the geopolitical ones should not be underestimated either. Since May 2025, the United States has been pursuing a policy of aligning its domestic medicine prices with the lowest prices in comparable developed countries. The logic for the companies is simple: a low price somewhere in Europe may cost them dearly in America. Initial analyses show that in the first year after this policy was announced, over one third fewer new medicines were launched in eleven EU Member States than in the preceding year. The decline is not attributable to the American policy alone - other factors also play a part, including the new common European rules for the assessment of medicines. For rare disease medicines the decline is, for now, much smaller - around 10%. The conclusion, however, is clear: companies have a serious reason not to hurry with launching new medicines in countries with lower prices. For a country like Bulgaria, this is a serious warning.

And one more worrying signal. Several gene therapies approved in Europe have been withdrawn from the market for commercial reasons - not because they do not work. The discovery is only the beginning; what follows is putting a workable system in place: who pays, how and when, and who will follow up the patient for years on end - up to 15 years in the case of gene therapies. Health systems operate on annual budgets, whereas a gene therapy is usually administered once, while the benefits, the risks and the need for follow-up continue for years. That is why access to treatment today depends not only on the scientific discovery, but also on the readiness of the health system to administer it, to pay for it and to monitor the outcome.

How is Europe responding – and will the patient in Bulgaria feel the European changes?

The good news is that rare diseases are now a global priority. In May 2025, the World Health Assembly declared them one in a dedicated resolution, and in 2028 it is due to consider a draft ten-year global action plan.

In the European Union, between 27 and 36 million people live with rare diseases, and Europe has a paradox of its own: it generates medical discoveries, but often loses them. Around one quarter of scientific publications in biotechnology are European, yet only about 10% of the venture capital for the sector remains in Europe. The discoveries are made in Europe, but they are turned into medicines - and into successful businesses - elsewhere, often in the United States.

Europe opens the doors, but each country passes through them at its own speed. Pricing and reimbursement remain a national responsibility. There is also the European route for planned treatment in another country - for some of the most complex therapies it is the only one, but it is often slow and administratively burdensome. And something is missing: Europe has a plan to beat cancer, but it still has no common plan for rare diseases. The European Parliament is working on such a call, and I hope it will become a reality.

Where does Bulgaria stand in this picture?

Judging by the official statistics - in the middle. According to the latest survey by the European Federation of Pharmaceutical Industries and Associations (EFPIA), of the 168 new medicines approved in the EU in 2021–2024, 77 were available in Bulgaria as of the beginning of 2026 - around the EU average. But while in Germany the time to access is about two months, in Bulgaria it is more than 600 days.

These statistics, however, measure the inclusion of medicines in the public reimbursement system - in Bulgaria, that is the Positive Drug List. With rare diseases the picture is different: a large share of the therapies are prescribed and dispensed outside the List - as medicinal products that are not authorised, or are not distributed, in Bulgaria. Many of them are never officially placed on the Bulgarian market, and yet they do reach patients - through the named-patient procedure (the individual access procedure).

Your company supplies medicines from various parts of the world for individual patients in a small country. What are the advantages and disadvantages of being a trader operating such a model?

The numbers speak for themselves - Bulgaria's population is about 6.4 million and shrinking: in 2025 alone, the natural population growth was minus 49 thousand. Nearly one quarter of the people are aged 65 or over. Gross domestic product per capita in purchasing power standards is 32% below the EU average - on a par with Greece, the lowest in the Union. And 36% of health expenditure in Bulgaria is paid directly out of patients' pockets - the highest share in the EU. If we were guided by these figures alone, no business plan would ever choose rare diseases in Bulgaria.

The disadvantages are clear. For any given rare disease, the patients are often no more than a handful. Each patient is a separate project - a separate protocol, a separate order, a separate delivery, often under controlled temperature. And the costs of licences, qualified staff, cold chain and documentation are almost the same whether you deliver one pack or a thousand. When quantities are limited, the small market is last in line. The financial risk is not to be underestimated - we often pay the manufacturers in advance, while we wait months for payment from the system. Last but not least, there is the predictability of the rules - for a business that plans deliveries months ahead, this is the costliest risk.

The advantages, however, are just as real - and it is precisely because of them that this model exists. Even as it stands, the regulatory framework allows treatment with a medicinal product authorised in another country, including outside the EU, where treatment with the medicinal products authorised in Bulgaria is impossible or has produced no result. This matters, because over the period 2001–2024 the FDA approved more than three times as many orphan drugs as have been authorised in the EU. There is no minimum order volume requirement - we can secure a delivery even for one single patient. Specialised expertise - regulatory, logistical, commercial - and relationships with manufacturers in a number of countries, including small biotechnology companies with no representation in Europe. For them, we are the channel through which the medicine can be delivered when Bulgarian physicians prescribe it.

And there is one paradox that explains our mission better than anything else. Once a medicine is authorised and placed on the Bulgarian market, the named-patient procedure no longer applies to it - and we lose that supply. We regard this as a success. Our role is to be the bridge until the road is built. A small market is a disadvantage for business. It must not be a disadvantage for the patient.

Beyond the individual patient - how does securing these therapies contribute to the development of medicine in Bulgaria?

Far more than it may seem. The medicine of the future often begins with rare diseases. The first gene therapy authorised in the European Union was for a hereditary disease that affects no more than one or two people per million. The first CRISPR gene-editing medicine approved in the EU is for two hereditary rare blood disorders - beta-thalassaemia and sickle cell disease. Many of the new technologies, the flexible regulatory approaches and the models for patient involvement are applied first in rare diseases and only then make their way into other areas of medicine. A country that secures these therapies for its patients also develops its own medicine. A country that stands on the sidelines falls behind.

Every modern treatment administered in Bulgaria is experience for Bulgarian physicians, pharmacists and nurses - in working with the most complex products, in monitoring effect and safety, in building teams of different specialists. When treatment is possible only abroad, the knowledge and the money flow out of the country. When it takes place here, they stay and accumulate.

Diagnosis follows treatment: once a therapy exists, early diagnosis takes on a new meaning. From March 2026, newborn screening in Bulgaria covers six diseases instead of three - spinal muscular atrophy, severe combined immunodeficiencies and cystic fibrosis have been added. This is a major step, and its value comes from the fact that, for these children, there is now something that can be done once the diagnosis is made.

The 24 European Reference Networks for rare diseases bring together more than 1,600 specialised centres from 375 hospitals. As of the end of 2024, seven centres from Bulgaria are full members, and the National Centre of Public Health and Analyses describes our participation as “highly limited”. To join these networks, a centre must have experience and patients. And experience and patients come when treatment is accessible at home.

Every treated patient can provide data on the real-world effect of the therapy - for the registries, for the European assessments, for the next studies - if we collect those data systematically. Bulgaria already has more clinical trials per capita than the EU average. Experienced centres attract further trials, and trials mean earlier access to new therapies for the participating patients.

About 70% of rare diseases begin in childhood. In a country that is losing population and ageing, every child who receives treatment in time and then goes on to study and work is an investment. So is every parent who is not forced to give up their job to care for a seriously ill child. That is why I do not regard the treatment of rare diseases as an expense for a few cases. It is an investment in people - the resource Bulgaria is increasingly short of.

What should the State do - and what can Bulgaria achieve in the next three to five years?

Bulgaria cannot become a large market. But it can become a fast, predictable and reliable system - an advantage that does not depend on the size of the population. Six things are needed for that.

• A national plan for rare diseases - with measurable targets, clear responsibilities, predictable funding and a functioning patient registry;
• Reliable rules for the named-patient procedure. In law it is an exception, but in practice it is a permanent and necessary part of the system. The supplier should be selected not only on price, but also on the security of the supply chain, the delivery time and the ability to secure the entire course of treatment. The budget should be planned on the basis of the treatment actually approved, and payments should arrive on time;
• Active use of the European instruments: the joint clinical assessment - so that we do not duplicate analyses and can decide faster; the right to require supply from the marketing authorisation holder; joint procurement and joint negotiations with countries with similar markets;
• New payment models for the most expensive one-off therapies - payment in instalments and payment by results. The budget is annual, whereas the benefits and risks of a gene therapy are followed up for years;
• More Bulgarian centres in the European Reference Networks - with targeted support, because membership brings knowledge, consultations with leading specialists and best practice;
• Early diagnosis - continued expansion of neonatal screening and of genetic diagnostics.

And, finally - dialogue. The rules governing these medicines affect people for whom time is decisive, and they must be written together with the physicians, the hospitals, the patient organisations, the institutions and the suppliers - from the very beginning, not once the draft is already finished.

If you had to sum it all up?

In a small and ageing country, the timely treatment of every patient with a rare disease is an investment - in a family, in Bulgarian medicine and in the future of the country. Our job is to ensure that the medicine reaches the patient - of proven origin, fully traceable and on time.