Because of rare illness, Louise Moorhouse is on a special diet of pills or foul-tasting shakes. There's a drug that would allow her to eat like anyone else - she took it for three years during a clinical trial. But the NHS won't pay for it, reports the BBC's Deborah Cohen - and the drug company stopped giving it to her once the trial was over.
Imagine having to take more than 80 pills a day or drink shakes to replace everyday foods you can't eat. That's the reality for Louise Moorhouse, a 35-year-old teacher from Birmingham, who has a rare genetic condition called phenylketonuria or PKU.
The pills are "huge", she says.
"They're quite tricky to swallow. I think the most I have managed to do in one go is four. Any more than that and they come out my nose."
The shakes are preferable, but attempts to give them a fruity taste have not succeeded in masking their "stomach-turning" acidity. From time to time her stomach starts to reject them, Louise says. In which case, she goes back on the pills.
People with PKU can't properly digest the amino acid phenylalanine. Amino acids are the building blocks of protein and are broken down by the body to make our own proteins. But in people with PKU the levels build up, and can cause brain damage.
Louise says she has to completely avoid 80% of normal food, and the protein in her diet has to be severely restricted - which may mean weighing it on scales before eating it.
"I basically live on fruits and vegetables," she says.
Dinner dates are best avoided, she has learned.
"I avoid socialising with food if there's people there who I don't know," Louise says. "They may notice that sometimes I have to get my scales out and sometimes I have to send food back or it takes me a long time to choose food."
But for three years, in her early 20s, Louise was able to eat like anyone else.
That's because she took part in trials for a drug now called Kuvan (sapropterin hydrochloride) that was being developed by US biotech company, BioMarin.
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"I took part in the trial because I just thought, 'Wow, if this works it's just going to change lives,'" she says.
And for Louise it did.
"Kuvan allowed me to eat a completely normal diet. And it was it was almost like someone had opened curtains on my life and I could see everything in Technicolor," she says. "It just freed me up so much."
The dietician who had treated Louise as a child, Prof Anita MacDonald of Birmingham Children's Hospital, was one of the scientists involved. With help from her and Louise, BioMarin gathered enough evidence to show Kuvan reduced the levels of phenylalanine in many people with PKU. In 2007, it became the only licensed drug for the condition in the US; its European licence followed in 2008.
"Because the trial had gone so well and because it made such a difference, I was convinced that it would only be a matter of time before this drug - that we had proved worked - would be available to everyone who responded to it," Louise says.
But for NHS patients it wasn't. BioMarin put a £70,000 price tag on it, per adult per year - and the NHS thought it wasn't worth that.
"The drug was too expensive and the NHS decided that there wasn't enough evidence of efficacy of that drug at that time and so they said no to prescribing it," says Anita MacDonald.
It was a blow for Louise, who had to return to the pills and shakes.
"It was a massive shock to my system," she says. "I had to relearn almost everything. It had a massive effect on my concentration, my mood, my focus at work, my relationship."
The hope of an effective treatment for PKU had appeared on the horizon in the 1990s. A simple compound developed in a Swiss laboratory had been found to enable people with PKU to digest phenylalanine. It was then researched with public money and used unlicensed by many doctors.
The trouble was, PKU is quite a rare disease. In England it is estimated that between one in 10,000 and one in 14,000 people have PKU. So there was little financial incentive for a pharmaceutical company to turn the compound into a licensed drug.
Then in 2000, the European Commission introduced incentives to encourage the production of "orphan drugs" for people with rare conditions, ruling that companies would enjoy up to 12 years of market exclusivity.
The cost of orphan drugs
According to Dyfrig Hughes, professor of pharmacoeconomics at Bangor University, more than 165 orphan drugs have now been approved - and that in fact 50% of all drugs approved last year were for rare diseases. Companies find them profitable.
But critics say the profitability - and the high price - of orphan drugs does not reflect the amount of effort companies have had to make to generate them.
"We did one piece of work where we identified that 40% of orphan drugs are actually repurposed. That is they've been previously used for other purposes before they were granted orphan status," Dyfrig Hughes says.
With governments across Europe struggling with the price of drugs used to treat rare conditions, the BBC is aware that the European Commission is reviewing the incentives scheme.
In 2004, BioMarin - which specialises in drugs for rare conditions - bought the data from the early development of the compound to treat PKU. This meant that while it had to fund trials it didn't have to meet the costs of searching for an entirely novel chemical compound.
When Kuvan was licensed a few years later and the NHS refused to pay the hefty price, patients were stuck in the middle. This remains the case, even now that the NHS has come to recognise the efficacy of the drug.
"BioMarin have been asked to drop the price on many occasions but at the moment they have a patent," Anita Macdonald says. "They've got no competition."
BioMarin told the BBC the NHS has asked for an 80% discount.
"BioMarin is disappointed that the NHS England has not recognised the value of treating PKU patients with Kuvan, despite more than a decade of positive patient outcomes across 26 countries in Europe, Russia and Turkey," a spokesperson said.
An NHS England spokesperson said: "The NHS does not offer a blank cheque to pharmaceutical companies, instead the NHS works hard to strike deals which give people access to the most clinically effective and innovative medicines, and at a price which is fair and affordable, which is exactly what our patients and the country's taxpayers would expect us to do."
Most disappointed by the outcome were the people like Louise, who had taken part in the trial and identified Kuvan as what Louise calls "the holy grail for us". The BBC is aware of seven others.
"You want your patients to gain any benefit from the work that they've done. They've entered the trial in good heart. We as scientists enter the trial in good heart," says Anita Macdonald.
"I don't think it is ethical for patients to be involved in a trial and not continue with a treatment. Those patients put a lot of trust in the drug company and it's the least that could have been done for them to continue with that treatment longer term."
Indeed, there is a global medical ethics agreement for research, called the Declaration of Helsinki, which says provisions should be made "for all participants who still need an intervention identified as beneficial in the trial".
When the BBC pointed this out to BioMarin, the company said: "To the best of our knowledge, BioMarin is treating all known ex-trial patients. If there are any ex-trial patients who are not being treated and would like to be treated, they should talk to their treating physician and apply for treatment."
For Louise, who for 10 years since the end of the trial has had to maintain her diet of pills or shakes, this came as startling news. She burst into tears.
It had taken her years to conceive because of the difficulty getting her blood levels of phenylalanine down, she said.
"A lot has happened that didn't have to happen. All these years I could have been on Kuvan and I wouldn't have had so many issues.
"I feel so emotional - it's like winning the lottery."
Update 1 November 2019:Louise Moorhouse has now been receiving Kuvan for several months.
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