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Drug approval processes are evolving to get treatments to patients more quickly. But for terminal diseases, some say they aren’t changing fast enough. 

When Ruth Le Gal pours sachets of powder into a glass and mixes in water and milk, it’s a ritual with huge importance for her son, Leo. He suffers from the deadly genetic disease Duchenne muscular dystrophy (DMD). The Le Gals hope the powder can extend his life.

Although this drug has started to reach patients in a few European countries, it’s still not generally available in the UK, where the Le Gals live. They had to battle to get it, and such struggles pose a tough question for modern medical systems: How can people get faster access to drugs they desperately need?

The Le Gals’ only option has been flying across the Atlantic and back every eight weeks to participate in a clinical trial in Boston, Massachusetts. For boys with DMD, such trials have been the main hope, slowly expanding in recent years as drugs that target the disease’s genetic basis near the market. Yet studies have enrolled as few as 12 patients and set strict rules about who can take part, meaning the chances of getting onto one can be very slim. And while few families have to go as far as the Le Gals, the small number of centres running DMD trials usually leads to a costly and time-consuming travel burden.

Progress in drug development also opens up other options for patients who have exhausted alternative treatment options and don’t qualify for clinical trials. For them, many countries allow doctors to give life-saving experimental drugs under ‘named patient’ or ‘compassionate use’ schemes. Typically, these involve a patient’s doctor contacting government authorities or the drug manufacturer directly to organise access. A few countries, such as Spain and Turkey, are making the drug that Leo’s taking available through this route.

Yet clinical trials are carefully constructed to make sure the company behind a drug gets valuable data, and named patient-type access is not. And in the USA, where most insurance companies will not pay for investigational drugs, there’s also little financial incentive. Chris Garabedian, CEO of DMD drug developer Sarepta Therapeutics in Cambridge, Massachusetts, calls the named patient and compassionate use options a ‘get out of jail free’ card for the US drug regulator, the Food and Drug Administration (FDA).

“They can take the position that ‘We’re not ready to say this drug has a safety and efficacy profile that would warrant it to be used in every patient – but if you want to ask, and the company wants to give it to you for free, we don’t have a problem’,” Garabedian says. “Every parent I talk to believes that their child is the most deserving of compassionate use. We’re saying every one of these boys is deserving, and that’s why the drug needs conditional or accelerated approval.”

Europe has pioneered the ‘conditional approval’ approach, which seeks to broadly allow doctors to give their patients new drugs based on early trial data. The condition is that more data must still be collected, and the drug’s continued availability is dependent on what that shows. The first DMD drug targeting the disease’s genetic origin – the one Leo Le Gal is on a trial for – has gained this type of approval. And the European Medicines Agency (EMA) emphasises that it wants to provide even earlier access, and is therefore trying out a new approach called ‘adaptive licensing’.

“We invite companies to make proposals on how they can prospectively plan early access for a well-defined subgroup of patients, who will be suitable to easily identify the benefit versus risk balance,” says Spiros Vamvakas, head of the EMA’s scientific advice office. “Based on this the drug can be authorised, and then real-world data – not necessarily randomised clinical trials – can be used to expand the patient population.”

Adaptive licensing might hold promise in technologies like Sarepta’s. Its lead drug is designed to match the mutations that affect the largest DMD patient group, with later ones designed for less common mutations. However, the chemical structures of Sarepta’s earlier and later drugs will be very similar, so patient groups such as the UK’s Muscular Dystrophy Campaign are hoping they can avoid some approval steps. Although Nic Bungay, the charity’s director of campaigns, care and information, would like a single ‘platform’ approval covering different mutations that would allow this, he’s realistic about the chances. “I get the sense that the EMA is happier with adaptive licensing, and I think we'd certainly support that approach as well,” he says.

For Ruth Le Gal, none of these efforts would be quick enough. “Duchenne’s a medical emergency,” she says, “and when it’s an emergency you have to move quickly, but there’s just not the capability for that in the system.” She points out that the EMA can take 210 days to consider even conditional approval applications. “How many people are going to die in the next five years while we’re waiting to finish the testing for these drugs?”

Frustrated by the situation, the Le Gal family has appeared in their local media urging support for the UK Medical Innovations Bill. This proposed law is also known as the ‘Saatchi bill’ after its backer, advertising executive and Conservative Party chairman Maurice Saatchi, whose wife died of cancer. If enacted, it would mean doctors that ‘depart from the existing range of accepted medical treatments for a condition’ are not negligent, as long as they act ‘responsibly’.

The Saatchi bill has drawn fire from some solicitors and doctors for failing to protect patients adequately, but after some amendments (which sought to address the issue) has gained government backing. Even setting that criticism aside, Bungay sees practical issues in applying it to the as-yet unapproved treatments for DMD. “The questions haven’t been answered about who will fund those costly drugs,” he says. “I can’t quite see the mechanism whereby a local doctor will be able to reach out for a drug which potentially isn’t even being trialled in the UK, and has a huge price tag, and give that to their patients.”

But Ruth Le Gal underlines the potential for innovation with existing, cheaper, drugs that the Saatchi bill enables. “They’re currently doing trials with Viagra for Duchenne because it increases blood flow,” she explains. “Increased blood flow to muscles could protect against muscle deterioration. Viagra’s obviously licensed already, but you can’t just try it for Duchenne – they’ve got to go all the way back through all the phases of trials before it could then be approved for use.” In this case, Le Gal says, preventing people taking the drug so formal trials can be conducted is an unnecessary delay during which DMD sufferers edge nearer to death. “That’s where the Saatchi bill is saying: ‘Just let them try.’”

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