Hard News by Russell Brown

5

More on the repurposed hepatitis C drugs and their potential as a Covid-19 treatment

Back in April, I wrote about trials in Iran of a fixed-dose combination of two existing anti-viral drugs used to treat hepatitis C – sofosbuvir and daclatasvir –  that could point to an effective treatment for Covid-19 symptoms.

At the time, data from those trials was not available outside the hospitals that conducted them and their identification was a matter of some detective work at a distance by the Australian doctor James Freeman.

Overnight, per the press release below in the names of doctors in Iran, Brazil and the UK, those results were formally presented to the International Covid-19 Conference.  It's important to note that the three trials were small – totalling only 176 patients – and open-label. They do not confirm that   "sof-dac" is an effective treatment. But, in the words of the doctors, patients given the combination showed "significantly faster rates of clinical recovery and improved survival for patients hospitalised with COVID-19 infection."

In particular, as a Financial Times story this morning notes, the death rate for patients given the drug combination was 5% versus 20% for those who were not. The FT also quotes Dr Anthony Fauci:

Anthony Fauci, the head of the US National Institute of Allergy and Infectious Diseases and a member of the coronavirus task force, told reporters the results were “really quite interesting and provocative and encouraging”.

“We desperately need antivirals that can be given early on in the course [of the disease] to prevent individuals from requiring hospitalisation,” he said. “I’d encourage that we do further studies to nail this down.”

That's happening. There are now five randomised trials involving 2000 patients in Iran, Brazil, Egypt and South Africa, which should by October give a better idea of the viability of the treatment. If the results are positive, it would be good news for the world. The two drugs are generically manufactured as Hep C treatments in several countries and, if shown to be effective, would represent a Covid treatment that could be provided cheaply ( $US7 per 14-day treatment) and at scale.

That remains to be seen. But how we got to this point is interesting. There is no pharmaceutical company money behind the new trials and the key one in Brazil, representing half the total patients, only got off the ground because Dr Freeman personally provided some funding. A further $500,000 from the NGO Unitaid let it go ahead.

By contrast, huge resources have gone into the global Solidarity clinical trial project overseen by the WHO, which last week announced that its trials of hydroxychloroquine and an HIV antiviral combination have been discontinued. Only Gilead's remdesivir antiviral remains in active trials under Solidarity.

That doesn't mean there are no other treamtent trials in progress – to take the most notable example, dexamethasone has emerged as an effective treatment in trials in the UK. But it does raise real questions about the allocation of the really major resources.

New Zealand Hep C activist Hazel Heal, a longtime collaborator with Dr Freeman, also brought in donations from her colleagues in the Edmund Hillary fellowship. She's strongly of the view that the international research effort into Covid treatments is broken – and focused too much on vaccine development and too little on treatment options.

"Treatments have been starved of research dollars and patients to try them on because all the eggs are in the vaccine basket, which is a long way off giving us a solution. There are 150 funded vaccine trials around the world at the moment – and for treatment, just Solidarity, which was for three drugs and is now only for one.

"Even if remdesivir is shown to be effective at ICU, the US has bought up all the global production for the next several months. So the world has given up its ICUs and its research dollars to research one drug that's not very good which will only be available to Americans."

Even after Brazilian researchers conducted in vitro research that showed that daclatasvir was active against the SARS-CoV-2 virus and published the results as a pre-print three weeks ago, efforts to have their work replicated in the US were stymied because all necessary resources were committed to vaccine development.

She says in the longer term, the sof-dac combination is probably "an answer, rather than the answer," comparing it to AZT in the early days of HIV treatments, but adds:

"Repurposing small-molecule drugs that come in tablets is the important work that shoud have been done methodically around the world– and it just hasn't been. It's a failure at the international organisational level."

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Hepatitis C Treatment shows promising efficacy against COVID-19 in first studies.

Definitive results expected in October

Results presented today at the International COVID-19 conference show significantly faster rates of clinical recovery and improved survival for patients hospitalised with COVID-19 infection given two Hepatitis C drugs - sofosbuvir plus daclatasvir.  These results are from three relatively small, open-label clinical trials in a total of 176 patients.  These trials were conducted in three cities in Iran (Abadan, Tehran and Sari), during their first wave of the COVID-19 epidemic.

After 14 days of treatment, 94% of patients taking sofosbuvir/daclatasvir showed clinical recovery versus 70% on control treatment.  The death rate for people taking sofosbuvir plus daclatasvir was 5%, versus 20% for people taking control treatment.  One of these trials was not properly randomised, but clinical recovery rates were still significantly higher for sofosbuvir/daclatasvir in the two randomised trials (96% versus 80%).  Small, open-label trials could be prone to biases, so these results need to be seen as preliminary, unless confirmed with larger double-blinded placebo controlled trials.  

“Laboratory studies have shown that daclatasvir has antiviral activity against SARS-CoV-2.  Daclatasvir also penetrates well into the lungs, where COVID-19 infection can be concentrated.  In laboratory studies, sofosbuvir has only marginal antiviral activity against SARS-CoV-2.  Sofosbuvir plus daclatasvir already has a well-established safety profile in the treatment of Hepatitis C.  Worldwide, millions of people have been cured of Hepatitis C using this treatment.”  Dr Thiago Souza, Laboratório de Imunofarmacologia, Rio de Janeiro, Brazil.

“This treatment is being developed with no support from the large pharmaceutical companies.  All our funding is from governments, Universities, or donor agencies such as Unitaid. If this treatment proves to be effective, it could be made available worldwide as a cheap generic treatment costing approximately $7 per 14-day treatment course.  Sofosbuvir plus daclatasvir is already available at these prices in India, Pakistan, Iran and Egypt.  There is already enough generic sofosbuvir and daclatasvir mass produced to treat millions of people if this drug proves effectiveness in large trials.  We want this treatment to be affordable for anyone with COVID-19 infection, in any country.”  Dr Andrew Hill, Liverpool University, UK. 

“In spite of the encouraging initial results, we believe it is too early to reach a verdict.  Larger, well-designed studies are required to confirm our results.  A network of 5 randomised clinical trials has been set up, to test sofosbuvir plus daclatasvir in over 2000 patients with COVID-19, in Iran, Brazil, Egypt and South Africa.  The largest of these trials is double-blinded and placebo controlled.  By October, we should know from the trial results if this treatment could be approved for worldwide use.  Conducting research amidst a pandemic with overwhelmed hospitals is a challenge and we cannot be sure of success.  Sometimes treatments look promising in early trials but then fail later on.  

In the future, we will also be evaluating daclatasvir at higher doses and as part of dual or triple combination treatments.”  Professor Shahin Merat, Tehran University of Medical Sciences, Iran. 

Dr Andrew Hill, Senior Visiting Research Fellow, Liverpool University

Dr Thiago Souza: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo 10 Cruz (Fiocruz), Rio de Janeiro

Professor Shahin Merat: Digestive Disease Research Institute, Tehran University of medical sciences

9

The cannabis referendum: the evidence

If the government has not lined up behind a "Yes" vote in this year's cannabis referendum the way some reformers would have liked, one entirely laudable thing it did do was commission some science around the public's choice.

That science landed today, in the form of the report from an expert panel convened by the Prime Minister's Chief Science Advisor, Professor Juliet Gerrard. The panel was specifically not asked to make a recommendation, but instead to summarise the evidence on legalising and regulating cannabis.

The result is some quite admirable science communication, with evidence available in at-a-glance summaries and FAQs, and in detail. There's even an accompanying 25-minute video by Shirley Horrocks:

It would be redundant to go through all of it here, but it would be fair to say the panel seems to have found more common ground on the social harm caused by the current criminalisation of cannabis than on the public health consequences of legalisation and regulation, as observed in other jurisdictions, although it does indicate that on balance, legalisation will make it easier to get help with use problems and also make research easier to conduct.

Indeed, that's what Professor Gerrard focused on in an interview ahead of today's release

"Instinctively when people hear the word harm, they think about the medical harm. Less well documented is the social harm - people getting kicked out of school for a drug offence, a drug conviction on a record which could affect employment prospects and cascade into a series of social harms.

"The people in that situation are disproportionately young, disproportionately male and disproportionately Māori."

The panel has, however, found a consensus that cannabis is less harmful overall than the two currently legal social drugs, alcohol and tobacco – and on most measures at that. Whether legalising cannabis leads to a substitution of cannabis for alcohol is less clear.

 The at-a-glance page correctly notes a "progressive softening of the law" on cannabis in New Zealand, culminating in last year's Misuse of Drugs Act  amendment directing police discretion away from prosecution and towards a health-based response. It also observes that "enforcement may continue to discriminate against Māori and young men."

Cannabis arrests have already declined sharply over the past decade, and the panel says that the number of convictions "is also likely to decrease over time". Yet within this slow slide into de facto decriminalisation, leaving production and supply as criminal enterprises is "likely to continue to give rise to and boost organised and opportunistic crime."

What the panel doesn't canvas, but which I fret about sometimes, is some evidence that under decriminalisation (and permissive medicinal schemes) in US states, public health outcomes – and rates of youth use especially – were worse than under legalisation.

New Zealand Police are increasingly disinclined to prosecute cannabis possession – and the courts are granting discharges for people caught with as many as 20 plants, especially if there is some evidence of medicinal intent. I do worry about sliding into a messy, unregulated space the way Canada did. Youth use climbed right up to legalisation there, then stabilised and declined. Remember last year when Patrick Gower agonised on TV about the dab bars of Vancouver, where people were inhaling powerful concentrates? They actually predated legalisation by years and the new federal law is being used to close them down.

In Horrocks' video, Dr Irene Braithwaite of the Medical Research Insitute of New Zealand draws a distinction between "recreational" use and the medicinal use permitted and regulated under last year's Misuse of Drugs (Medicinal Cannabis) Regulations. On one level, this is just clearing up the dfference between two laws, but as we know from research conducted in the past year by both MCANZ and Massey SHORE, there is a large group of  New Zealanders using cannabis illegally in ways that are at least as much therapeutic as "recreational". Adult use of cannabis isn't just one thing.

As controversial as it's proving to say, that community isn't necessarily going to switch wholesale to prescribed GMP-standard cannabis products – and certainly not before there are many more products and GPs willing to prescribe them. The referendum is about whether we should continue to criminalise those people too.

My impression overall is that there's more in the expert panel's consensus to please reformers than the people who favour continued prohibition of cannabis, especially in the area of social harms. To be honest, that was to be expected.

Whatever any of us takes from this exercise, I think the government is to be commended for requesting it and the PMCSA for delivering it in the way it has. Bravo.

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There's another new presentation on the implications of cannabis legalisation – and in a place where you might not expect it.

Auckland Transport has just published a swathe of cannabis-related papers presented to its board last month and it while most of those are external documents attached for the reference of the board (including health and safety advice from Canada) , the discussion document presented by AT staff is solid, sensible stuff.

What's missing for now is active consideration of a switch from urine to saliva testing within AT itself. Saliva testing offers a much better measure of actual impairment, it will be fairer for employees and there's now a New Zealand Standard for it. AT should be talking about this to its employees and their unions.

But there's time for that. For now, AT deserves plaudits for getting out in front of the issues. Other organisations could follow suit.

8

Paula Bennett and the Scientology leaflets

I wrote earlier in the week about the Scientology front organisations Drug Free World and Drug Free Ambassadors and their quite prominent role in anti-cannabis reform "coalition" assembled by Family First and a new local branch of the American prohibitionist organisation SAM.

It turns out Family First aren't the only ones helping the Church of Scientology market itself to vulnerable people. National's former drug reform spokesperson Paula Bennett did her bit too.

On February 24, Bennett was the guest of honour at a meeting on drug reform – one of a series of such meetings where she spoke – staged by the new National Party candidate for Upper Harbour, Jake Bezzant. It seemed to go well, with Bezzant writing afterwards on Facebook:

Thanks to all who attended and engaged at our drug reform public meeting with Paula Bennett in Westgate tonight - standing room only! 

I appreciate hearing from across our community on the topic. It's vital we're informed as the cannabis referendum nears, along with calls for further drug liberalisation.

Among the audience was Aucklander Emlyn Revell-Nash, who noticed, as he put it to me, "something fishy" about pamphlets that were put out at the meeting. They were from The Foundation for a Drug Free World – which is, as my earlier post this week observed, a front for The Church of Scientology. Says Emlyn:

What was weird was the pamphlets were not only on the table along with the spam signup forms; but Jake announced the last question would be taken from this particular old woman, in her sixties or seventies, who was from Drug Free World. He and Paula then proceeded to hand out these leaflets.

Emlyn accepted a pamphlet, confirmed its provenance, and took a couple of pictures of it.

The source of this material – if not the explicit connection to Scientology – was pretty obvious. I suspect Bennett and Bezzant simply weren't diligent enough to enquire into exactly what they were literally handing out. (Although Bennett possibly should have been, given that she was in government in 2012, when Drug Free Ambassadors got taxpayer money to print 130,000 copies of an "education booklet" that was distributed to New Zealand schools.) Perhaps some shock-horror literature just suited their purpose.

Just in case, Emlyn let them know:

I'd be interested to know if anyone else who attended Bennett's meetings saw this material there – or anywhere else, for that matter. Feel free to get in touch by commenting below or, for more privacy, clicking the envelope icon at the bottom of this post to email me.

To be clear, it is absolutely not the case that anyone who opposes the legalisation and control of cannabis as proposed in the forthcoming referendum is in bed with Scientology. But this is recruitment material for an abusive cult and we need to be able to have our debate on the referendum without it. We also really don't want MPs or candidates handing it out.

29

The Scientology front operation behind the "No" campaign on cannabis

Last night, One News ran a follow-up story to its Colmar Brunton poll results on the cannabis referendum, headed here as Government accuses big American anti-cannabis group of interfering in NZ politics.

In truth it wasn't just the government: Justice minister Andrew Little, National's Shane Reti and the Greens' Chloe Swarbrick all appeared on camera to express unease about the entry to the referendum fray of the American lobby group Smart Approaches to Marijuana.

SAM is controversial in the US too, not least on account of its tireless efforts to avoid revealing who bankrolls its activities. Say Nope to Dope, which was founded by Family First's Bob McCoskrie, yesterday swiftly issued a press release on behalf of SAM-NZ denying that the local "No" lobby was being "bankrolled by or controlled by US organisations".

Further "SAM in the US are not telling our coalition how to run our campaign, and have not contributed one cent to it."

But Say Nope to Dope did, three weeks ago, issue the press release announcing the formation of SAM-NZ, to be fronted by Aaron Ironside, a Christian life coach, former radio DJ and longtime associate of McCroskie, who had also been announced only days before as Say Nope to Dope's new spokesperson.

Yesterday's press release included a list of other individuals and organisations who are part of the "No" coalition. It includes quite a number of well-known conservative voices, such as school principal Pat Walsh and Jess McVicar of Sensible Sentencing Trust. There are individuals with a commercial interest in talking up the drug war, such as Methcon's Dale Kirk and Drug Detection Agency owner Kirk Hardy.

There are various conservative Christian groups, along with a couple of senior members of the New Zealand Muslim Association (but not, it appears, the association itself). It's about what you'd expect: people with vested interests and people and organisations that routinely oppose liberal social change, along with a few who have entered the fray because they're genuinely concerned about cannabis legalisation.

But there are also four names from an organisation that will be less familiar: Drug Free World. That will be Drug Free World Aotearoa New Zealand, which set up a Facebook page earlier this year. It appears to have evolved from Drug Free Aotearoa, which was estabished by Taranaki woman Rose Denness in 2012. Denness's name will be familiar to people who have studied the Church of Scientology.

Yes, she is a Scientologist, and Drug Free World Aotearoa New Zealand is Scientology front, along with Narconon and various others listed by then-Green MP Kevin Hague in Parliament in 2009. Said Hague at the time:

I am not a person with a religious belief myself, but I do not object to churches providing social services, provided that the church connection is transparent and that the service is not a front for recruiting into the church. It seems to me that the Church of Scientology fails on both those fronts.

The "About" page of Drug Free World Aotearoa New Zealand's Facebook links directly to the website of the Foundation for a Drug Free World, a notorious Scientology front with a long history of wangling its way into official drug education programmes to peddle pseudoscience.

It even happened here: Drug Free Ambassadors, another Scientology front managed to get public money for 130,000 copies of a booklet distributed to New Zealand schools.

It's possible, probable even, that many of the people involved here in Drug Free World have no idea what it actually is. The old Drug Free Aotearoa used to wrap itself in tikanga so the links weren't obvious, and Drug Free Ambassadors claimed a "partnership" with Māori wardens. Some may have come to it via the "briefings" that can be booked via its Facebook page (the first one is free, of course).

If some elements of this anti-reform coalition are opaque and questionable, its embrace of a harmful Scientology front is actively alarming. And it says something about the nature of the active opposition to cannabis law reform in New Zealand that it's there.

6

Towards the referendum: this might actually be a trend

Back at the beginning of April, when we had much else on our minds, I wrote this post urging some caution in interpreting the results of the latest Horizon poll, conducted in February, on voting intentions in this year's cannabis referendum, which was paid for by Helius Therapeutics.

I wrote that the structure and style of the questions:

... sets up the proposition in quite an obvious way, with legalisation and regulation implicitly presented as the prudent and responsible course of action: “controls” versus “no controls".

It’s not dishonest: it’s literally the argument most of us make for reform. But it has very probably had a bearing on responses, and was crafted with that in mind.

Well, Horizon and Helius have published another poll, using the same questions and structure, and it really does seem to show a rising trend towards a "Yes" vote in September:

There's a difference in the way the reports are reported though: in Horizon's release on this latest poll, results for the question At this time, do you think you will vote for or against legalising cannabis for personal use in New Zealand? are listed before those on prohibition and its outcomes in New Zealand, not after. I suspect that doesn't actually mean a change in the order of the questions, but I'll check.

The actual overall increase in intending "Yes" voters is modest: from 54% to 56%. But that's up from 39% in August last year. And there are increases over February regardless of who respondents voted for in 2017. Striking increases in support among Act voters (from 45% to 70%) and New Zealand First voters (from 46% to 53%) may reflect a small numbers problem, but even among National voters, 31% would be prepared to overlook partisanship and vote "Yes", up from 27% in February.

In demographic terms, only the over-65s aren't showing majority support for reform.

What's happened between the two polls? A sharp tilt towards Labour in party voting intentions for one thing. But Horizon polled its panel between June 4 and 10 – days after the New Zealand Drug Foundation's 'On Our Terms' campaign launched on June 2.

The message of the campaign is very clearly emphasised on its home page. The page leadline is: It's time to take control of cannabis on our terms. The referendum is characterised as the Cannabis Control Referendum. It lists 8 key control measures of The Bill. And that's all above the fold. The word "control" is further emphasised with the use of colour.

This aligns with the way the Horizon poll questions talk about Controls over growing and selling personal use versus Continuing with no controls.

I don't think Helius and the Drug Foundation are really colluding over this – they're simply discovering what argument resonates with the public in their research.

So we're not only seeing a steady increase in support for reform – albeit in response to a poll structured to cultivate that support – we may also be seeing what the winning argument might be.

The challenge for reformers as September approaches will be to keep that the argument – and, ideally, to separate that argument as much as possible from political partisanship. In the run-up to an election, that might not be easy. But it's becoming clear that's the job.