How the patient voice is becoming vital for drug approval

Rebecca Sanders from Lipodystrophy UK tells us how the patient voice helped convince NICE to approve a much-needed drug for this rare disease, and explores how regulators and pharma companies can help make patient involvement in HTA more impactful.

When England’s drug reimbursement watchdog NICE was on the fence about approving lipodystrophy treatment metreleptin, it was stories from patients that helped it get over the line and into routine use.

Rebecca Sanders, CEO of Lipodystrophy UK, the charity that spearheaded the patient involvement at NICE’s committee meetings for the drug, says that perspectives from people who live with the disease every day were essential for overcoming the shortcomings in the data.

“The numbers are never going to tell the whole story about quality of life,” she says. “There are so many other aspects of the condition that impact not just the patient themselves but their extended family, their carers and their children.

“Without the patient voice it’s difficult for researchers and regulators to understand what that all means. Stakeholders are well-meaning, but you need the personal touch in order to really get across the gravity of the situation.”

A misunderstood condition

This was particularly important for metreleptin because lipodystrophy is a condition with many misunderstood social and mental health impacts on top of its severe medical effects.

Lipodystrophy is a rare disease with two different forms. Generalised lipodystrophy results in a total loss of subcutaneous fat cells. Partial lipodystrophy results in a partial loss, but the fat that remains is redistributed in inappropriate places around the body.

This can lead to metabolic abnormalities including insulin resistance, diabetes, and elevated levels of blood lipids (such as high cholesterol).

“People often say, ‘Oh, that’s great. You haven’t got fat cells, you can’t put on weight’ – but they don’t necessarily understand that fat cells have quite an important metabolic function,” says Sanders. “The impact of that lack of fat is actually very similar to the impacts from obesity.”

The loss of fat cells also results in the loss of one of the hormones they produce, leptin –  which, among other things, controls appetite. This means that lipodystrophy patients can feel hungry all the time, no matter how much they eat.

“Some people don’t see that as a big deal, but in practice that means your body constantly thinks you’re starving to death,” says Sanders. “That causes all kinds of difficulties, especially when the main mode of management for lipodystrophy is diet.”

In addition, the loss or redistribution of fat can have major effects on people’s appearance.

“With generalised lipodystrophy, patients can often look quite gaunt and undernourished, and with partial lipodystrophy you can either have an unusual redistribution of fat or a lot of excess fat on your face and chin. That makes people feel very body conscious and uncomfortable.

“Partial patients can also have muscular hypertrophy, which results in extra muscle mass. Many patients, particularly female patients, really struggle with that because as a society we tend to associate muscular appearance with masculinity. That can also have severe mental health impacts.”

Patients often experience hot flushes, but can be so conscious of their appearance that they will still dress to cover up their body, even in hot weather.

“I know people that moved to the Middle East so that they wouldn’t be questioned for wearing trousers and long sleeves in hot weather,” says Sanders. “People go to those kinds of extremes because they feel so uncomfortable with themselves.”

Building the patient voice

Sanders was diagnosed with lipodystrophy when she was 17.
“The first thing I did was ask the hospital whether there was a support group, but it turned out there wasn’t anything,” she says. “So I asked if I could write a letter that they would pass on to other patients if they wanted to contact me.

“For a long time, I contacted other patients in that way. More and more, I felt that we needed something organised, so I put together a website with another patient. Through that, we had a forum and we organised meetups. That was really helpful and people got a lot out of that.”

The patient community continued to grow from there, with Sanders working with Addenbrooke’s Hospital to organise patient support days where people could talk to specialists and other patients.

“That was an opportunity for people to share things that had worked for them, whether that be medical interventions or more mundane things like body moisturisers that had worked for their skin.”

Eventually Sanders felt she would be able to do more with a formal organisation.

“In 2016 I put my ideas together, got a group of people on board as trustees, then went through the application process to become an official charity in 2017.”

This allowed the group, now called Lipodystrophy UK, to have a higher level of organisation, apply for funding for particular support projects, and provide a stronger voice in patient advocacy.

Sanders is a geneticist by training, and says that this has helped her in her interactions with scientists and regulators.

“I am fortunate in that by being a scientist myself I understand a lot of the complexities behind the condition that other people sometimes struggle with. It also means I tend to be taken a bit more seriously as a voice when speaking to people like clinicians, researchers, or pharma companies. It shouldn’t be that way, but it is.”

Fighting for access

As an official charity Lipodystrophy UK has also been able to act as an expert voice in NICE appraisals for the lipodystrophy treatment metreleptin – where patient insights into the misunderstood aspects of the condition proved invaluable.

Before being approved, metreleptin had gone through two previous owners, and had been rejected for funding on the grounds of inadequate evidence in 2019. Eventually it was bought by Amryt who, keen to get the drug licensed, resubmitted it to NICE in 2020.

“One of the difficulties in getting licensing was that early on the drug had been given to patients on a named-patient basis and for compassionate reasons, rather than as a formal clinical trial,” says Sanders, noting that this issue is not uncommon in rare diseases.

“Unfortunately, that resulted in not having the organised, rigorous dataset that is usually required for NICE submission.”

Sanders has been on metreleptin treatment herself for over 10 years, and from the start has been involved in fighting for access to the drug, engaging with the pharma companies, clinical researchers, and NICE.

“NICE is good at encouraging conversations with patient stakeholders in these types of meetings, and we’ve been able to speak as a charity at all of the appraisal meetings for the drug. They’ve also made sure to reach out to patients who are not trustees of the charity,” she says.

NICE gave the patient community several opportunities to submit evidence.

As part of this, Lipodystrophy UK did a survey of the community and presented the data to the committee, while also highlighting individual statements and quotes.

Sanders says that these personal stories gave NICE a chance to understand the real impact of the treatment even when, on the surface, the data didn’t seem to show much efficacy.

“They definitely helped get the human story across. It’s so easy to concentrate on the numbers, the money, and the facts and figures, but that doesn’t tell you anything about the people and how a disease actually impacts them on a day-to-day basis.

“For example, if you say to someone you’re hungry all the time they often don’t understand what that really means because most people, certainly in the western world, have no idea what it’s like to feel truly hungry.

“Throughout the process we were involved with NICE and all the other stakeholders to make sure that those aspects were not forgotten about.”

More communication, earlier

These patient testimonials helped push metreleptin over the line into approval, and the drug was finally approved for routine use on the NHS in January 2021.

There are plenty of rare disease drugs that aren’t so lucky, though, and Sanders says that in order for other treatments to avoid metreleptin’s early reimbursement difficulties more communication between every stakeholder at every stage is vital.

In particular, she says, many of metreleptin’s initial struggles came down to a lack of communication with patients from the earliest stages of development, which led to the wrong kinds of data being collected.

“The earlier HTAs, researchers and pharma companies can start that engagement the better.

“For example, the first committee meeting for metreleptin didn’t touch on how important the hunger aspect was, because nobody had that discussion with us in advance.

“After that meeting, we were able to tell the company how important it is to explain why metreleptin helps with that aspect, and how that impacts quality of life – but of course it would have been best to have that discussion upfront.”

And in the case of HTA bodies in particular, early communication means patient groups can be in the best position possible to share the right information with them.

“We were fortunate in that sense because our particular case went on for several committee meetings and we had opportunities to resubmit information, but in cases where there’s only one meeting patients might only have one chance to get it right.”

This means making sure patient advocates are clear on what opportunities for submission exist, and what kinds of information would be useful for the committee.

“For example, are they interested in what carers think? Do they want to assess quality of life? It’s important right from the beginning to have clarity on that, so that the focus of the patient submissions is right and the HTA is getting what they need. Then the patients feel like they’ve done justice for everybody.”

And on a more mundane note, regulators should make sure that meetings themselves are accessible to patients no matter their needs.

“Not everybody will be able to travel across the country to attend a meeting, for example,” says Sanders. “For me that means I would have to take the day off work and deal with the fatigue that comes with travel. COVID has shown everybody that there’s more we can do remotely to resolve that, and NICE has been good about recognising how important that is, but of course there’s always more that can be done.”

Going even further back in the process, there can also be benefits to reimbursement outcomes further down the line if the patient voice is taken into account at the start of drug development.

“It’s really important for pharmaceutical companies to engage with advocate communities when planning studies or deciding to provide a drug on a compassionate use basis, so that they know they’re capturing the right kind of data,” says Sanders.

“Again, the kind of data that clinicians are usually interested in, while very important and necessary, doesn’t always capture the aspects that matter to patients, and one of the big problems with metreleptin was that the data wasn’t collected properly at the beginning.”

Sanders’ work is not done now that metreleptin has approval in England, and Lipodystrophy UK are also working with clinicians in Scotland to see if a similar appraisal process for the drug can be applied there.

On top of that, the charity is providing guidance to other patient groups around the world, advising them on what they need to consider when getting involved in HTA processes.

“We’re also working to develop a global collaboration of patient groups for lipodystrophy,” she says. “When you’ve got more people behind you, the patient voice can carry more weight, and that’s especially important in a rare disease.

“There are obviously variations in culture and drug assessment processes in different countries, but at the end of the day patients are suffering from the same conditions and want the same things.”

About the author


George Underwood is the editor for pharmaphorum’s Deep Dive digital magazine. He has been reporting on the pharma industry for seven years and has worked at a number of leading publications in the UK.

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