Pharmaceutical reform poses challenges for innovation in undiagnosed diseases

The European Commission’s proposed pharmaceutical reform could impact innovation in treating rare or undiagnosed diseases in Europe, industry representatives and patient associations told EFE.

Daniel De Vicente had to wait until he was 36 to be diagnosed with a condition that had troubled him since he was six months old: acid sphingomyelinase deficiency (ASMD), a rare and degenerative disease for which there is still no approved treatment in Spain.

But for the last six years, he has been part of a clinical trial for six years, which has allowed him to “reverse” the progression of his disease, benefiting four other Spanish patients as well.

“Spain is among the European countries where a large number of clinical trials are conducted, but then there’s not good access to treatments compared to other European countries. It’s a bit of an inconsistency,” De Vicente, who is a board member of the Spanish Federation for Rare Diseases (FEDER), explained in an interview with EFE.

Only about 58% of drugs approved by the European Medicines Agency (EMA) are marketed in Spain, compared to 90% in Germany, with a 629-day delay in Spain, according to the ‘Indicator of Waiting Time for Access to Innovative Therapies’ (WAIT) report.

The delay is even longer in Eastern European countries like Poland and Romania, particularly for orphan drugs, which treat rare diseases, according to the report, published in April by the European Federation of Pharmaceutical Industries and Associations (EFPIA).

Addressing Access with Incentives

To address this, as part of its pharmaceutical reform proposal, the European Commission suggests incentives for manufacturers who offer their product in all 27 member states within the first two to three years. 

“We want to create a single market for medicines in Europe, and a central element of this is more equal access to medicines for all patients, no matter where they live. We cannot have second-class patients. Everyone deserves to have access to existing treatments for their disease,” a Commission spokesperson told EFE.

Currently, the company that has developed a new drug is the only one allowed to use the data from its clinical trials for the first eight years. Other companies cannot sell their generic derivatives until another two years have passed, making the total period of exclusivity 10 years, or up to 11 years in some cases.

If the Commission’s proposal is successful, which still needs to be debated and approved by the European Parliament and member states, this period would be reduced to eight years.

It can be extended in particular cases: if medicines are launched in all EU countries (+2 years), if they address unmet medical needs (+6 months), or if comparative clinical trials are conducted (+6 months).

For rare disease medicines, the standard duration of market exclusivity will be nine years. Additional years of protection will be applied if companies address a high unmet medical need (+1 year), launch the medicine in all EU states (+ 1 year), or develop new indications for an already authorised orphan medicine (up to 2 extra years).  

Icíar Sanz de Madrid, international department director at Farmaindustria, argued that meeting the Commission’s new requirement is “impossible” due to the complexity and fragmentation of the EU’s pharmaceutical market.

“Incentives won’t change access as it is national procedures that govern access, pricing, and reimbursement conditions,” she told EFE.

From the Spanish Association of Orphan and Ultra-Orphan Drug Laboratories (AELMHU), Beatriz Perales shared similar concerns. “The Commission’s proposal doesn’t reflect the reality of marketing drugs in Europe,” she told EFE.

“It does not reflect the existing differences between each member state in terms of financing an orphan drug, nor the difficulties it would pose for small and medium-sized enterprises to market their drugs across the entire EU in a short period of time.”

Simone Boselli, public affairs director at the European Organisation for Rare Diseases (EURORDIS), stressed that “in rare diseases, if you don’t do it across borders, you don’t get more patients” for the investment to be worthwhile for the laboratory, because these kinds of illnesses have a prevalence of fewer than five cases per 10,000 people in the EU.

The Commission argues its system will expand access to “about 70 million more people” in the EU, maintaining one of the “world’s most generous” incentive systems and a faster EMA authorisation process.

Unmet medical needs

Another aspect of the reform that concerns EURORDIS, AELMHU, and Farmaindustria is the introduction of two concepts associated with greater market protection: “unmet medical needs” and “high-priority unmet medical needs”.

The first concept refers to innovative drugs that treat life-threatening or “severely debilitating” diseases, provided their approval signifies a “significant reduction in the morbidity or mortality” of the condition and there is no existing product in the Union market to treat it, or if there is, it poses too many risks.

The second category is reserved for rare diseases where the introduction of such treatment would represent an “exceptional therapeutic advancement”.

These concepts are too strict, in Boselli’s words. He warned that “very, very few of the therapies that we have are transformative or curative“, fearing the loss of incentives depending on the interpretation of this requirement.

Farmaindustria’s Sanz de Madrid pointed out that they “advocate for a much broader definition” which includes, for example, diseases that significantly deteriorate the quality of life.

Amendments proposed in the European Parliament’s Public Health Committee (ENVI) follow this line, but it is too early to predict the Parliament’s final direction as the debate is expected to extend well beyond the June 2024 European elections.

If the proposal is passed without changes, the Farmaindustria representative believes it would send a “clear signal to foreign investors” that pharmaceutical innovation in Europe is going to be “unprotected”.

“We have calculated that by 2030, the market share in research would be 54% in the United States and 25% in the European Union” if the reform is approved, she warned.

[Edited by Sandra Municio/Giedrė Peseckytė/Zoran Radosavljevic]

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