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Brussels wants drugmakers to plow more money into researching cures for currently untreatable rare diseases, and has come up with new enticements to make that happen.
But not everyone is convinced the planned regulation will be the panacea promised by the European Commission, especially when it comes to treatments that work on the genetic codes of patients themselves, an area of special promise for patients with rare diseases.
“It’s dividing the world … into black and white,” said Alexander Natz, secretary general of the European Confederation of Pharmaceutical Entrepreneurs (EUCOPE), of the Commission’s proposal to give special bonuses to drugs for rare diseases that are judged to meet a “high unmet medical need.”
EUCOPE is a lobby group representing medium-sized and smaller drugmakers including those working in highly specialized rare disease treatments. Its leader, Natz, expressed reservations about the incentive program during a working group on rare diseases organized by POLITICO.
He said while he supported the basic idea of giving special rewards to companies that develop rare disease medicines, he worried that the Commission’s fix was too blunt an instrument.
Rare diseases aren’t so rare
Patients suffering from rare diseases often have shorter lifespans and require frequent hospital treatments. But while one in 12 Europeans has one of the 6,000-odd known rare diseases — equal to 36 million people — individually each disease affects few patients.
That makes them a hard sell for drug companies that already face long odds when it comes to developing an effective cure — and then have only a restricted number of people eligible for such therapies, limiting sales.
It was to address this problem that the Commission in 2000 introduced new legislation creating special incentives for rare disease medicines (known as “orphan drugs” because a rare disease without a treatment was previously described as an “orphan”).
It was a success: Before the legislation only eight rare disease medicines had the backing of the European Medicines Agency, while since it was introduced over 200 have been approved.
Now the EU executive is doubling down on this approach.
Under the proposed new pharmaceutical legislation put forward by the Commission, new medicines that meet a “high unmet medical need” — defined as medicines for rare diseases that are an “exceptional therapeutic advancement” and which result in a “meaningful reduction in disease morbidity or mortality” — would benefit from an extra year of market exclusivity, the period of competition-free sales when a new medicine makes the most money.
Considering that a successful medicine during this period can make as much as €1 billion or more annually, an extra year is significant. An extra two years, meanwhile, would be an even bigger bonus — and that’s what has been proposed by the European Parliament in its version of the text that is up for a vote next week.
That sounds like a big incentive for gene therapy developers, but as Natz explained, the devil is in the details.
Bad timing
About 80 percent of rare diseases are caused by a genetic mutation. The nature of these hereditary illnesses makes them difficult to treat with cheap, small-molecule medicines, usually in pill form. The good news is that the emerging field of genetic medicine holds promise of treatments, and perhaps even cures, for many of these conditions.
The industry, however, worries that while in theory more incentives are great, in practice even the most promising treatments, such as gene therapies, are unlikely to qualify.
It all comes down to timing, explained EUCOPE’s Natz.
To incentivize investors to back risky gene therapy developments, they need to know early on if their candidate will qualify for the bonus year of market exclusivity. But under the current plans, the decision to award that label is taken at the end of the treatment’s development, once it’s authorized.
In the meantime, a rival drug could already have entered the market, meaning the candidate no longer qualifies for “high unmet medical need” status. That risk makes it hard for investors to factor in the possible reward, defeating the purpose of the incentive, Natz said.
At the same time, he added, the incentive is awarded “too early.” To qualify for the reward, developers also have to demonstrate exceptional improvements compared with current care. And while “one would expect a cell or gene therapy to deliver an exceptional therapeutic advancement,” the license decision is often based on somewhat scant data, he said.
That’s because rare disease patients are hard to find, making comparative clinical trials — where medicines are tested against the best standard available — often unethical or impossible if there are no existing treatments.
“Thus, depending on the ultimate definition and requirements to demonstrate [high unmet medical need], we risk that some advanced therapies, despite being transformative, miss out on the label,” Natz added.
Government agencies that decide whether to pay for new drugs tend to resist efforts to dilute evidence standards. They argue they need as much clinical trial data as possible to judge whether a new drug is worth their money.
That’s especially true of gene therapies, which often come with an eye-watering price tag. In the U.S., Lenmeldy, a treatment for the rare disorder metachromatic leukodystrophy, has a list price of $4.25 million, making it the most expensive drug in the world.
Speaking at the same working group, a Commission official who asked to remain anonymous defended the proposal, noting the bonus would be on top of the existing orphan drugs framework, and that a medicine that didn’t qualify for high unmet medical need would still be incentivized.
The official also pointed out that the orphan drug designation is also confirmed at the time of approval, and that it has been successful in stimulating orphan drug development.
Moreover, for medicines that don’t qualify for high unmet medical need, other incentives are available such as the PRIME designation, which grants regulatory support and a quicker assessment. Orphan medicines that don’t qualify for high unmet medical need can still benefit from scientific advice on the conduct of studies and are eligible for national and EU incentives to support research in rare diseases.
“We continue to have [a] very competitive system of incentives in Europe,” the official said.
This article is the product of a POLITICO Working Group presented by Sanofi and was produced with full editorial independence by POLITICO reporters and editors. Learn more about editorial content presented by outside advertisers.
