Orphan medicines Pharma package provisions unleash uncertainties, stakeholders warn

There are more than 6,000 rare diseases, with 27 different healthcare systems governed by diverse rules and principles, with vast differences for orphan medicines payments. The new Pharma Package seems to focus on bridging some of the regulatory gaps, but stakeholders warn of the risk of amplifying uncertainties.

It is estimated that one in 12 people in the EU has a rare disease. However, the number of orphan medicines (therapies dedicated to rare diseases) authorised in the European Union is just over 240, showcasing the complexity and difficulties surrounding drug development in the field.

Simone Boselli, EURORDIS, Rare Diseases Europe, Public Affairs Director, commented to Euractiv: “Every rare disease patient deserves access to treatment, no matter the rarity of their condition.” But complexity seems to run through all aspects of rare diseases, especially when attention turns to access to medicines, and as talks on the pharmaceutical legislation revision hit up.

Numerous studies have shown differences in patient access to orphan drugs, mainly “due to variations in national budgets in national healthcare budgets, health insurance, and reimbursement systems”, as one states.

Dr Alexander Natz, Secretary General of the European Confederation of Pharmaceutical Entrepreneurs, which represents small and mid-sized pharmaceutical and biotech companies in Europe (EUCOPE), explained to Euractiv, “We have 27 different health care systems that are governed by completely different rules and principles, and there is no harmonisation in the level of who pays for medicines, what are the price mechanisms for medicine, and so on.”

For Natz, access to medicine, especially orphan drugs, for patients across the EU is a responsibility of the pharmaceutical companies. However, it depends strongly on the priorities of the health system.

“There is an obligation for companies to be more flexible and find ways to make centrally approved medicines available to more EU citizens than in the past. This discussion is at the centre of pharmaceutical legislation for good reasons, and it’s a discussion that we want to be part of,” he said.

He adds that what sometimes gets forgotten is “that it is also about the health care systems’ willingness to pay and the decision-making in that health care system.” He cites the example of gene therapies that have been released in some countries but not in others.

Germany leads by example

In this “patchwork of different systems,” as Natz describes it, Germany seems to be ahead of the curve.

According to Natz, the country has introduced measures that have led to more than 95% of the orphan medicinal products being available to German citizens.

Under one of the mechanisms, an orphan drug is assumed to have additional benefit from the start, and it is made immediately available on the market as long as it does not exceed a financial impact threshold of €30 million.

“But we’re evaluating. Are you much better or a little bit better?” he remarked. “It’s speedy access. Of course, there are mandatory discounts to be given, and this isn’t free pricing. There are price negotiations conducted for these orphan drugs as well”, he comments. This system has led to the majority of companies going to Germany first. “Most orphan products are launched in Germany on day one, pretty much two weeks after marketing authorisation,” he added.

Even though Germany is a country that can better afford it, negotiating prices with companies is a part of the system: “It’s not a home run; you don’t get any price you’re charging; there’s no free pricing for the next three years; it’s only free pricing for six months when they do the HTA assessment.”

“So, that shows, by fine-tuning your health care system, you can do a lot to get those products to patients. I think more than 95% of rare disease medicines have been launched in Germany since 2011,” Natz told Euractiv.

Joint efforts

Orphan medicines struggle to move through conventional mechanisms of evaluation and reimbursement, as not all member states have structures and services to enable the process. But limited data for long-term clinical benefit or even on budget impact deters payers from making the decision to ‘green light’ an orphan drug until more real-world evidence is available, putting its availability on hold.

For Natz, it makes sense to have one Health Technology Assessment (HTA) system that assesses a medicine from the same perspective, as its value doesn’t change depending on which member state the patient taking it is residing in.

“But we need to get it done in the right way,” Natz warned, pointing out the importance for orphan drugs of recognising higher unmet medical needs, the fact that few medicines are available, and the fact that patient populations are much smaller, hence smaller clinical trials.

“HTA for an orphan medicine makes sense as long as we leave the pricing discussions to the national level”, he adds.

Pharma Package uncertainties

According to a study conducted by Dolon, the provisions relevant to orphan medicines proposed by the Commission as part of the revision of the pharmaceutical legislation would hamper the development of 45 products in Europe in 2020-2035 (or a decrease in innovation of 12%).

“The outcomes of MEPs’ ongoing negotiations on the proposed legislative reforms to boost rare disease medicine development are massively important to our community,” Boselli commented, referring to talks on the update of the EU’s pharmaceutical legislation.

“We are comforted to see that in the current state of negotiation, the modulation of incentives for market exclusivity remains strong,” he said, but considers it crucial that: “these incentives are structured to both promote fairness and position Europe as a leader in pharmaceutical innovation, especially for the rarest and most severe conditions.”

He also welcomes the proposal for voluntary centralised procurement, “which promises more equitable treatment access through collective bargaining – a boon for smaller EU Member States and patients with ultra-rare diseases.”

“However, we still harbour concerns that extend to the use of ‘High Unmet Medical Needs’ in legislative language. The definition of such terms is critical, requiring early and inclusive dialogue to ensure legislative actions are effectively targeted and impactful,” he added.

According to Natz, “There are some concerns primarily about unpredictability.”

Political objectives

As he sees it, the political objective of guiding efforts to unknown therapeutic territories is understandable, and companies are open for modulation, “but it needs to be done in a way that the level of exclusivities is clear from the beginning.”

Natz explained that the launch conditionality in which developers only receive their full exclusivity period for launching in all member states within a limited timeframe is “not an easy exercise,” claiming that it will fester uncertainty.

“If we want to gain and not lose ground towards the US, we need to tell investors what they will get in terms of exclusivity if the project [of developing an orphan drug] is successful,” he adds.

He also suggests considering other simple, flexible, and less administrative tools, like working with the cross-border health directive (patients can seek treatment in another EU country and be reimbursed at home, provided certain conditions are met).

He considers that the new definition of ‘significant benefit’, which requires a substantial part of the patient population to benefit from an orphan medicine, also adds further unpredictability to the system, as “substantial” is not defined.

In addition, Natz points out that the proposed new legislation, which provides only one additional year of regulatory data protection for a new indication (which may be granted only twice), forfeits the advantages gained from the existing orphan legislation, which grants a separate orphan market exclusivity period for every indication for different rare conditions.

Complexity of new indications

As he explained: “Developing the same compound into another indication takes almost the same effort as developing it in the first place. Adding a new indication is a complex exercise, which deserves more than one year”, he said, pointing out the risks of discouraging efforts of looking into the possible benefit of a compound for more rare conditions with no incentives.

When asked how access can be improved, Natz turns to member state competence once more. “The first thing is learning from the member states’ experience. Because access will remain a member-state decision,” he said.

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