Hepatitis C – new hope on the horizon

Pharmac has recently started funding new drugs that have amazing curative effects for more than half of people in New Zealand with hepatitis C. The wait continues for those for whom the drugs are not suitable, but there may be good news on the horizon. Russell Brown reports.

On 10 August last year, PHARMAC published an RFP seeking feedback on a plan to fund hepatitis C treatment with a new generation of direct-acting antiviral drugs (DAAs) in the year to come. Given that patients experience DAAs functionally as a miracle cure with few side-effects – but at the same time they cost at least $80,000 for a 12-week course of pills – it was an exciting step.

The agency noted the clear recommendation of its Pharmacology and Therapeutics Advisory Committee that two medicines containing Gilead Sciences’ sofosbuvir should be funded with a “high priority” for the most seriously ill hep C patients, including those either side of a liver transplant. The committee had recommended only a “low priority” for the rest of the 50,000 New Zealanders infected with hep C – a decision it said was “based solely on fiscal risk”.

What actually happened was completely different.

PHARMAC subsequently announced it would allocate funding priority not on the basis of the severity or stage of the liver disease hep C causes but according to the genotype of the virus with which patients were infected.

It’s safe to conclude that PHARMAC was unable to agree an acceptable deal with Gilead, which has opted for a high-price strategy on its DAAs in an attempt to recoup its development cost before they are outmoded. It turned instead to another supplier, AbbVie, and is now fully funding treatment with the AbbVie drug combination VIEKIRA PAK.

But VIEKIRA PAK can only treat genotypes 1 and 1a of the virus, which account for about 55 percent of the 50,000 New Zealanders with hep C. It will not cure patients with genotypes 2–6. Treatment for the latter group with Gilead’s Harvoni (ledipasvir with sofosbuvir) will only be funded if they are in the final stages of liver disease with fully decompensated cirrhosis. At that stage, their life expectancy is short.

“How many people would meet those criteria? I’d say about 50 people a year,” says Ed Gane, Deputy Director of the Liver Transplant Unit at Auckland City Hospital.

“You’re talking about 0.1 percent. It’s pretty small. But if PHARMAC hadn’t done this deal with AbbVie, I think we’d still be treating only a tiny percentage.”

Gane is not alone. Dunedin-based peer advocate Hazel Heal describes PHARMAC’s decision as “morally right”. And it is already showing results.

“We’ve gone from treating around 250 patients a year to 500 in the first two months,” says Gane. “On current numbers, we’re likely to treat about 3,000 a year, which is a 12 to 15-fold increase in the first year.”

Part of the reason for the uptake is that the safety and relatively low monitoring requirements of the DAAs allow for care in the community rather than hospital clinics.

“We’ve had about 120 patients with genotype 1 come forward for treatment here at the liver unit,” says Gane.

“Of those, because we attract the sickest patients, around half have cirrhosis or other significant complications where it wouldn’t be safe to treat them in the community. Everyone else, the other half, we’ve said ‘Would you like to go back to your GP?’, and every one of them has said yes. So we have not treated them – we’ve sent them back to their GPs to be treated.

“So we’ve made a decision early on that, if we’re going to eliminate hepatitis C, we need to get GP input, we need to get them to endorse us. And the best way to do that is to send them back some easy patients to treat so they can see it can be done. It’s a wonderful thing to be able to offer somebody who has a chronic disease a cure. It provides satisfaction for them, but it also provides satisfaction for the GP so he or she will look for other people to treat.”

GPs have been allowed to prescribe DAAs since 1 October 2016, but the process of bringing them up to speed on the use of the new drugs continues. Gane and Catherine Stedman of the University of Otago have created an explanatory document for doctors’ professional bodies, the medical information service bpacnz recently published a step-by-step guide for GPs and Gane wrote a detailed guide for the most recent Hepatitis Foundation newsletter. Gane expects to continue talking to doctors in person.

But the most significant step – one specifically allowed for in the Ministry of Health’s rollout – may yet be delivery through needle exchanges and community alcohol and drug services, and that requires the engagement and support of peer workers. Gane said that lesson was learned in pilots run via district health boards in the Bay of Plenty and the Wellington region from 2011 to 2014.

“Over three years, they tried to engage at needle exchanges – and they couldn’t. They went in as an external organisation without any engagement with peer workers who worked there, and over the three years, the number of people they managed to enrol and test – not treat – could be counted on one hand across the two regions. It was an abject failure.”

A pilot staged this year in Auckland has achieved very different results. Nurse Victoria Oliver, who had been working in opioid substitution services, was recruited by Gane to run a clinic room at the East Street needle exchange.

“There’s a plinth, a bed to lie on and a washbasin. We take the portable fibre scanner down there two days a week. And over the few months she’s been there, Victoria has already had 60 people come in and be diagnosed. She’s interviewed a lot more than that.”

Oliver describes the pilot as “a service within the client’s setting, where they feel comfortable. They’re people who are often stigmatised and ostracised because of health professionals’ belief and subsequently their own perceptions. It’s one of the things that stops them coming into hospitals because people make punitive judgements. People catch hep C predominantly through intravenous drug use, and there’s a lot of stigma around that.”

Gane says the outreach was inspired by the approach of the Australian Government.

“They’ve done a fantastic job in getting treatment outside the hospitals. And that’s based on a lot of work that several NGOs have done in Australia, previously for HIV. You don’t even have to be a general practitioner – if you’re working in an isolated area of the country, provided you’ve been accredited through training, you can prescribe.

“What their government has said is, if you want to get rid of hep C, you have to remove all the barriers to treatment – and one of the biggest barriers is still having to come to hospital. There are many populations who have high rates of hep C who are marginalised from treatment because they either can’t or won’t come to hospital clinics.

“And if you are ever going to eliminate hep C, you should prioritise for treatment the people who are still transmitting the virus. You shouldn’t be marginalising and not treating them. They should be amongst the first lot you treat.”

The problem, at least for the next year or two, when new drugs are expected, is that there is no PHARMAC-funded treatment for the very large majority of the 22,000 people infected with genotypes 2–6. The option for them is to import far cheaper generic medicines, but there are problems with that in some parts of the country (see sidebar), and many people in the infected cohort cannot afford even the $1,500–2,000 cost of generics. Oliver says around a quarter of the patients she has diagnosed are in that category.

“They can’t even borrow it, it’s just not in the realm of possibility,” Heal agrees. “There has to be an option for those people. There are people I can’t help who, for want of $1,500, are going to remain unproductive and unable to work.

“The Ministry of Health can’t buy these generics, but in the meantime, I really think that the Ministry of Social Development could pay for people. It would be a huge saving for the government in the long run. It addresses genotypes 2–6 in a really cheap way. They’re just paying the patient back for their treatment in the way that they might for counselling.

“$1,500 is the cost of a life – and every day of a life from this moment forward.”

Oliver describes the experience of offering infected people such an effective treatment as “fantastic, amazing. It’s lovely to be able to provide people with hope – and a cure. To be able to cure a virus like this – I graduated in 1986, and it’s something you hardly ever hear of.”

There is more to come in this story. Gane says there are two or three drug combinations in trials that will hopefully be funded by PHARMAC and will be “the same medicine, the same duration for everyone, regardless of genotype or stage of disease. And that’s going to make thing so much easier." 

Side bar: Generic DAAs are okay

The country’s leading hepatitis C specialist, the Society of Gastroenterology, the Hepatitis Foundation and Europe’s leading liver study organisation endorse the use of generic DAAs for hep C patients not eligible for PHARMAC-funded treatment. So why is the Southern District Health Board (DHB) refusing to tell its patients generics are even an option?

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A year ago, Hazel Heal was told her liver was deteriorating rapidly. The hepatitis C-related cirrhosis she’d borne for 18 years – and through two punishing and unsuccessful courses of interferon – was on the verge of decompensation, and she needed treatment urgently.

She had already called a real estate agent about selling her house to pay for DAA treatment when she heard about the Fix Hep C Buyers Club, the generics-importing scheme founded by Tasmanian Greg Jefferys. She sought a prescription from Tasmanian doctor James Freeman, travelled to Australia to pick up her medication – and was cured.

She now helps Jefferys with club administration and does “a lot of letter writing and media interviews”.

This year, she wrote to Southern DHB Chief Executive Carol Heatly urging the Southern DHB to amend its policy of not presenting generics as an option for patients not covered by PHARMAC. Heatly replied that, if the DHB “were to promote a drug that was unlicensed, was not manufactured by the current patent holder (and so therefore completely unable to be registered in New Zealand)”, it would be in breach of its obligations. In a subsequent letter to Heal, she wrote that it would be “futile” to discuss the issue further.

Heatly has since left her role, but her successor Chris Fleming confirmed to Matters of Substance that “our position has not changed” and “Southern DHB clinicians do not write prescriptions for the hepatitis C treatments you refer to as they are unlicensed medications”.

He described the medications sourced by Fix Hep C, which are manufactured under licence from Gilead and others in India, as “copycat generics”.

The disagreement centres largely on the standard letter Medsafe provides for importation of unapproved medicines, which includes a boilerplate warning that unapproved medicines could be counterfeit or contain harmful substances. Whether that warning applies to the Fix Hep C process, which is associated with the ‘Redemption’ trial operated by Freeman and supported by the European Association for the Study of the Liver, is another matter.

“I can’t understand that,” says Ed Gane of the Southern DHB’s stance.

“We certainly prescribe plenty here. If you have genotypes other than genotype 1, you should at least have the option of paying for your own treatment, which includes generic. And I think the only ethical thing to do if you are testing for hep C is to have that discussion.

“If we see someone diagnosed with genotype 3, we’ll say, ‘Sorry, but VIEKIRA PAK will not work for you, we expect that PHARMAC will have a treatment funded for you within the next one to two years. But in the interim, if you really want to be treated, you can import your own generics.’ And I would refer them to the Fix Hep C Buyers Club.”

Although the monitoring requirements for DAAs are relatively low, Gane says a local prescription (which Medsafe requires anyway) is important. He has written a detailed guide to importing DAAs via Fix Hep C, including recommendations on the best drug combinations for different genotypes, in the latest Hepatitis Foundation newsletter.

Gane is far more wary of generics manufactured in China and Bangladesh, which lack the facilities to make the ledipasvir component of Gilead’s Harvoni product, which helps absorption from the gut. But he says the 11 manufacturers producing under licence in India, where Fix Hep C sources, are a different matter.

“These are the same medicines that Gilead is making in the States. They’re good medicines.”

Photo credit: prx.org