Inside WA's Cannabis Story
Written by Jan Hallam
Thursday, 26 October 2017
Print E-mail

201711-medicinal-cannabis-capsules-budsWestern Australia is emerging as a key state in the development of a viable medicinal cannabis industry in Australia. Cultivation licences have been issued to at least two WA companies that Medical Forum has ascertained, even though the Office of Drug Control (ODC) declined to name the recipients of the eight licences issued so far.

One company is ready to plant its first crop locally and the other has entered into an agreement with Tasmanian Alkaloids (which grows 6% of the world’s legal opiate crop) to cultivate and manufacture in Tasmania with future potential to expand into growing in WA. Security of assets is strict and mandatory.

With TGA approval, local medicinal cannabis could be available by June 2018, if not before. To date, the ODC has issued four manufacturing licences, nationally. However, a further licence to manufacture is required from the TGA, which can only be granted for an existing facility. Tasmanian Alkaloids holds one of these rare licences.

We have also discovered that a considerable amount of research is being planned at Telethon Kids Institute, Curtin University and the WA Sleep Disorders Research Institute into the efficacy of various formulations of cannabis for brain cancer, pancreatic cancer, sleep disturbance, and eczema. So far the ODC has issued five research licences.

Hard work, less fun

Then there’s the business side of things. After an influx of players and the initial flurry of ASX listings, the reality of entering a highly regulated, big capital investment market has lost some of its shine for less-committed groups.

Australia is highly unlikely to head down the US route of cannabis cafes and a ‘recreational’ market, so young guns looking to be in the vanguard of a cool green brigade for local legalisation will be disappointed. What is being established is a strongly regulated medical model.

There are also private companies who are taking a steady-as-she-goes approach to see how the market develops before going down the public listing route. So while it is crowded now, the cannabis market is expected to distil into a core of participants with serious medical and pharmaceutical intentions.

Of course, there is the question of demand. It’s a hard thing to quantify because local medicinal cannabis products are only now filtering onto the market. Much of the demand has been met in the grey to black areas of the market. Last year, before legislation was passed, Deloittes Access Economics prepared a cost-modelling report for the ODC and Department of Health.

It used data collected by the University of Sydney, in partnership with MGC Pharmaceuticals, which put expected patient numbers across three medical conditions – HIV/AIDS, Multiple Sclerosis and Epilepsy – would be about 30,400 a year. In addition it was estimated there would be demand for 995,827 treatment sessions a year among cancer patients (actual patient numbers were not known).

Anecdotally, consumer demand in Australia is strong – at least strong enough to achieve legislative change. However, access to the product is putting the brakes on demand for two main reasons – restricted supply, which is set to improve rapidly over the next 12 months, and reluctance of the medical profession to prescribe, which is expected to take longer to turnaround.

We explore these issues with some of WA’s strategic players in the corporate, scientific and regulatory areas.

The Regulators

Legislation to allow the cultivation, production, manufacture and prescription of medicinal cannabis took effect on October 30, 2016 with both federal and state governments having a hand in regulating every step of the process.

Medicinal cannabis containing tetrahydrocannabinol (THC), the psycho-active element of the 104 cannabinoids present in the plant, became a controlled drug (Schedule 8) of the Poisons Standard on November 1, 2016. (Preparations with 2% or less of other cannabinoids are listed as Schedule 4.)

The ODC is tasked with regulating to prevent diversion and illicit use, and controls licences and permits to cultivate, produce, manufacture and import.

The TGA issues permits and actively monitors and assesses the quality, safety and efficacy of medicines before entry onto the Australian Register of Therapeutic Goods (ARTG). It also provides access to those medicines which have not been approved for use, which the TGA says will probably be the major route for patient access to medicinal cannabis products over the next few years.

Access to medicinal cannabis in Australia is available through the Authorised Prescriber Scheme and the Special Access Scheme. There has been a low response from practitioners to qualify for the Authorised Prescriber Scheme, which is no great surprise as the process is onerous. Among the hoops and hurdles, a practitioner must gain the approval of a specialty college or a human research ethics committee.

Where the colleges stand

The Royal Australian College of GPs has a position statement that calls for more research on the efficacy and safety of medical cannabis products and goes further by saying these products must be approved or registered through the TGA before they can be prescribed. That will take time.

The Royal Australian College of Physicians does not have a public statement on its website though it has participated in state inquiries and has made it plain its position won’t be hurried but it must be consulted “considering our members’ expertise managing the medical conditions involved”.

An ethics committee process is seen as too unwieldy and too slow.

So, at least for now, until more practitioners become authorised prescribers, the most common route will be the Special Access Scheme (SAS). Under the SAS, health practitioners can access unapproved therapeutic goods through notification or application pathways.

This is not as straightforward as it seems. A notification pathway is for patients who are likely to die without early treatment, so it is expected most doctors will go down an application pathway.

State gets in the act

A practitioner must get state approval on a patient-by-patient basis from an expert assessment panel. Medical Forum contacted the Chief Pharmacist, Mr Neil Keen, to explain the state process.

He said the panel was appointed in December 2017 and, as of September 13, 2017, five patients had been approved to use medicinal cannabis.

The panel comprises 13 medical specialists from the public and private sector with expertise in pain medicine, addiction medicine, oncology, paediatric neurology, adult neurology, public health, palliative care, psychiatry, immunology, toxicology and pharmacology.

The panel would only review applications for Schedule 8 medicinal cannabis.

“At present the notification pathway for medicinal cannabis includes multiple sclerosis. For other indications, approval to prescribe is via an authorisation pathway. As research evidence accumulates it is expected that additional indications will be added to the notification pathway,” he said.

“The process is modelled on the one in place for opioids, stimulants and opioid substitution therapy. These processes apply whether or not the medicine has been registered for use in Australia by the TGA.”

Too much red tape?

We asked Neil if state intervention was necessary given the oversight of the ODC and the TGA. He said the WA process for cannabis-based products was consistent with the well-established controls that apply to all Schedule 8 medicines.

“It is independent of, and has a different function to, the Commonwealth approval processes for unregistered medicines. State-based approvals are part of Medicines and Poisons regulations aimed at public health protection regarding drugs with high potential for dependence and abuse. The prescribing of any Schedule 8 medicine is subject to additional restrictions in WA and all S8 dispensing is observed through a prescription monitoring program.”

The research process attracts similar regulation. Researchers who plan to use a TGA unapproved cannabis-based product in a trial in WA must have:

  • Organisation/institutional human ethics approval
  • TGA approval for use of an unapproved therapeutic good in a trial
  • If a Schedule 8 product is being used, researchers will need authorisation from the WA Department of Health and applications for use in a trial would be reviewed by the panel.

The WA Players

AusCann

Dr Mal Washer, who as a former Member of the House of Representatives led the debate on drug policy reform, is chairman of AusCann. His daughter, businesswoman Elaine Darby, is the CEO and together they lead a very Western Australian team of business and science heads.

201711-Darby-Elaine-Ms Sep17Ms Elaine DarbyThe company has ODC licences to cultivate and manufacture cannabinoid medicines and while it is waiting on TGA permits to produce medicines and move ahead with building its own facilities in WA, AusCann has recently partnered with Tasmanian Alkaloids to grow and manufacture its products.

Until those become available, Elaine said it was importing and rebranding medicines from its Canadian partner, Canopy Growth Corp. It also has gone into partnership with licensed Chilean medicinal cannabis grower, JV DayaCann, and produced its first crop in May.

Canopy Growth produces, on licence, the Dutch-developed Bedrocan. Canopy and AusCann agreed two years ago that for an 11% share of AusCann, the WA company could access Canopy’s intellectual property and expertise, which included everything from plant genetics to the right medicinal formulations.

“No patient has used an AusCann product yet. We have applications in with the TGA and as soon as we get that clearance, we will apply to the WA panel,” Elaine said.

If Elaine had one wish, it would be able to call the product anything but cannabis.

Illicit stigma lingers

Unfortunately it does come with a stigma. If we could approach doctors and say we have this particular compound and this is some of the data of what it can do, I think the medical community would be excited and embrace it, particularly when we can show some of the emerging evidence of the opiate sparing effects of cannabinoids,” she said

 “But because they are cannabinoids they carry a stigma. While there is a need for regulation and oversight, the multi-layers are off-putting for some specialists who feel they are being second guessed. No doctor we’ve been interacting with is doing this on a whim. They are educated and are making informed decisions.”

Elaine said 70% of patients in Canada who were prescribed medicinal cannabis were taking it for chronic pain. She believes, over time, this will be the case in Australia as well.

“There have been a number of randomised placebo trials in the area of chronic pain, but only with small patient numbers. The US Academy of Science was tasked with a systematic review of all the clinical studies involving medicinal cannabis and when combined the results showed strong evidence for the use of cannabinoids in the treatment of chronic pain in adults and spasticity symptoms for MS patients and chemo-induced nausea,” she said.

201711-Cannabis-oilCannabis and neuropathic pain

“The Canadian Pain Society has recommended cannabinoids as third-line treatments for neuropathic pain, just behind opiates, and there are a lot of Canadian doctors lobbying for cannabinoids as a preference, particularly for neuropathic pain, because opiates don’t tend to work as well in that area.”

The cannabis product in the spotlight is an oil, which is swallowed. Elaine said that AusCann was moving to soft-gel capsules, which was an easier mode of delivery.

“It all looks very different to the illicit stereotype, but those images of adverse effects of illicit cannabis use still pervade and persuade. The reality of medicinal cannabis is that is has a much lower level of THC and people don’t develop a tolerance to its analgesic effects, so dosages don’t have to increase. The analgesic effects kick in long before anything else.”

“There has been a lot of hype about medicinal cannabis in this country and there’s no question that the potential market in Australia is significant. If we look at the patient group suffering chronic neuropathic pain, 1.8m people in Australia fall into that group alone. There is good evidence for its use.”

“The highly regulated environment will leave only serious companies intent on producing medicines for patients who will benefit from them. There are Australian patient groups keen to have their doctors advise them about whether these medicines are suitable for them or not. The Australian government is keen to have this happen as well.”

Getting confidence of doctors

“However, unless doctors are willing to prescribe these substances and go through the approval processes, nothing will happen. Our biggest challenge, as an industry, is to educate our medical community about cannabinoid medicines to get them to a place where they are comfortable to prescribe them for particular patients.”

“AusCann is investing heavily in doctor and patient education. We have engaged a Canadian physician, with years of experience in cannabinoid medicines, as chief medical adviser and we have appointed three medical liaison managers to develop accredited online courses and webinars, because doctor prescribing is our biggest hurdle. It will take time.”

“In Canada, doctors began prescribing, under their current model, in 2014 for about 7000 patients. Now that figure has grown to over 170,000. Doctors needed to see how it works with key opinion leaders showing the way in order to be comfortable. The Canadian doctors are the pioneers in the space. They had no one to turn to for issues like formulation or dosage or contraindications. We can learn from this experience.”

Little Green Pharma

Fleta Solomon is the managing director of a private company of 20 shareholders headquartered in Perth. The medical advisory team is headed by Dr Joe Kosterich and Prof Neale Fong.

201711-Solomon-Fleta-Ms Oct17Ms Fleta SolomonFleta told Medical Forum that Little Green Pharma (LG Pharma) was approaching the local market a little differently.

“We wanted to establish facilities and build a story to ensure the appropriate demand for medicinal cannabis and compliance were in place before expanding,” she said.

“Potentially we might look at the listed space down the track but it is easier at this stage to stay a private company without the complications of going public. The Government is learning, we’re all learning.”

Fleta said LG Pharma had been issued a licence for cultivation and production from the ODC and the permit to grow was pending.

“We have teamed up with a manufacturer (who cannot be named for security reasons) and we will look to get a Research and Development licence soon.”

Fleta believes the multiple layers of regulation will ultimately give Australian medicinal cannabis the edge over its international competitors, which enjoy less stringent oversight by their respective governments.

“The process is complicated but it needs to be and is the best thing for the Australian patient because the locally produced product will be high quality, effective and affordable. People can be reassured by that. We’re hoping regulations will relax a little for doctors so it is easier for them to prescribe and patients to benefit.”

Poised for action

Fleta said that once the permit to grow was issued, LG Pharma would be a few months away from product stage.

“We have a unique patented technology that can optimise bio-availability allowing a comparable clinical effect at a lower dose of cannabinoids. Amongst the range, we are hoping to produce a Schedule 4 (less than 2% THC) medicinal cannabis product which is simpler for doctors to prescribe.”

“Our products are indicated for epilepsy, MS, chronic pain, palliative care and chemo-induced nausea. Discussions are also underway with local and international researchers to examine the effect of medicinal cannabis on general cognitive deficit in dementia and PTSD.”

In her engagement with the WA medical profession, Fleta said she found many doctors to be cautious, yet open and wanting to know more information.

“If I had to guess, I would estimate about 10% of doctors are supportive of the use of medicinal cannabis, 10-20% who are set against it and the rest sit in the middle and are open to see what happens. Once a few of the specialists and GPs start prescribing, it will flow on,” she said.

While the Australian market is cautious, its potential is large.

Regulations cooling the process

“Everyone in the space believes they know where it’s going and that it is worthwhile commercially. It will improve people’s lives. Current regulations are slowing things down. Based on the existing infrastructure and regulations it will be slower than what has been proposed.”

[Estimates in the 2016 white paper prepared by Sydney University and ASX-listed MCG Pharmaceutical put initial expected demand at 30,000.]

“It would be overly optimistic to think that 30,000 people will benefit from medicinal cannabis straight away. Currently, there are only about 100 people receiving local product across Australia and a small number of authorised prescribers.”

“The problem I see is one of education. How do interested people even know who can prescribe when there is no website or community site where people can go to for that information? The Canadians struggled with that initially too, so we should learn from that in advance.”

“We are progressing, even though it may seem to be painstakingly slow. When doctors are comfortable prescribing the product and the patients are benefiting, demand will be strong and then we can start looking at other conditions medicinal cannabis may help. Research overseas has been very promising but we do need local research going forward.”

Fleta says that the eight companies that have cultivation licences can certainly cope with a growing demand – “they are all large commercial facilities” – and she warned that the government needed to take a relatively slow approach to growing the industry so the market was not saturated.

While the domestic market is just at the starting blocks, local medicinal cannabis companies no doubt have an eye on export markets down the track.

“Overseas growers look at Australia and almost laugh at the stringent regulations in place here but I think that’s a huge benefit because if anybody has a licence to cultivate and produce medicinal cannabis in Australia, that product will be seen as top quality overseas. And that’s thanks to government regulations.”

Zelda Therapeutics

This ASX-listed company emerged in 2016 from a reverse takeover of Gleneagle Gold, though Zelda has been around for more than a decade prior. The three major shareholders, according to the ASX, is former Gleneagle Gold miner Wayne Loxton, Jason Peterson, CEO and partner of CPS Capital, a corporate finance and stockbroking firm, and Gemelli Nominees, the private company of Harry Karelis, a founder and chairman of Zelda and board member of AusCann.

201711-Washer-Stewart-Dr Oct17Dr Stewart WasherMedical Forum spoke to co-founder and director Dr Stewart Washer (son of Mal), who was a stem cell researcher before becoming increasingly involved in medicinal cannabis.

He is focused on establishing and supporting sound research projects here and overseas to establish how and what conditions medicinal cannabis can help because he knows first-hand that if there is not enough evidence to satisfy the medical profession, Australian doctors will be loathed to prescribe it for their patients.

The US National Academy of Science’s review of medicinal cannabis trials, which Stewart describes as almost a Cochrane review, came out with positive evaluations for its use for chronic pain, MS spasticity and chemo-induced nausea.

“It also concluded there was reasonable and anecdotal data around insomnia, eczema and autism but more evidence was required. So that’s where Zelda decided to focus its research and define clinical trials in those areas,” he said.

Research kicks off in WA

“We are undertaking an insomnia trial in WA later this year with Dr Peter Eastwood and his team.” [Dr Eastwood is Senior Research Fellow at the West Australian Sleep Disorders Research Institute and at the School of Human Movement, at UWA. He is also Adjunct Associate Professor at the School of Physiotherapy at Curtin University.]

“We are also conducting clinical trials for insomnia in Chile. Their researchers have a lot of experience with medicinal cannabis and there is a very good regulatory and clinical trial system there along with experienced practitioners. An eczema trial using a topical formulation and an autism trial will also be conducted there.”

Zelda is also partnering pre-clinical cancer research in Spain with Prof Manual Guzman and Prof Cristina Sanchez from the University of Complutense, who are on the trail of cannabinoids and their potential to affect the growth of tumours, initially focusing on breast cancer.

“There is a great deal of anecdotal data from the US on cannabis having a positive effect in cancer, but this is enough evidence to design and conduct some proper studies. That’s why we’ve gone pre-clinical on this to an animal model because we really have to define what works and what doesn’t before we move to a clinical trial,” Stewart said.

“Professors Guzman and Sanchez found cannabis formulations appeared to work against triple negative breast cancer, which is out of bounds for Herceptin or hormone treatments. Guzman and Sanchez saw a different mechanism of actions in the cannabinoids, which work on cancer cells while leaving the healthy ones alone, so it is exciting research.”

Telethon Kids involvement

“We are also establishing research projects here in WA. We are partnering with Telethon Kids Institute for cell line studies in animal models for brain cancer later this year.”

“And one of the world’s leading researchers into pancreatic cancer, Prof Marco Falasco, has come with his research team to Curtin University from Italy. He will also be investigating cannabis formulations for pancreatic cancer. There is a lot of exciting work to be done.”

One of the obstacles facing the acceptance of medicinal cannabis is, unlike modern pharmaceuticals, the cart has largely gone before the horse when it comes to medicinal cannabis use and research. People have been using cannabis medicinally for millennia up until the 1930s when it was banned in the US.

Eli Lilly, Parke-Davis (now owned by Pfizer) and Squibb (Bristol-Myers Squibb) all had cannabis-based products until the 1930s. In the 1990s, there was the new-wave of ‘compassionate’ use in the California followed by approval for its medical use in Canada in 2001. Now Australia, in 2016, has joined in.

Stewart described the interest in cannabinoid research, in part, as retrofitting, or showing evidence for current use, which is being facilitated by doctors who see the benefit-risk ratio as too high to ignore. However, research is also expanding into new medical territories that if found effective could change the pharmaceutical landscape considerably.

Hunting down receptors

Prof Raphael Mechoulam at the Hebrew University in Jerusalem is undertaking studies to locate and identify a group of endogenous cannabinoid receptors in the mammalian brain. He’s found the receptors for THC, CBD CB1 – 100 more to go!

“This is a whole new field of medicine that is opening up. While that work is going on, we must ensure that this complex green gloop we are growing and manufacturing is the same time every time. We have to ensure our manufacturing is standardised before we even bother doing tests and that’s what the Australian industry is doing.”

He said Australia was in the perfect position to become world leaders in medicinal cannabis research.

“We have always been great medical innovators and we are taking a very medical approach to the prescription and use of medicinal cannabis. The cat’s out of the bag in the US with a fractured state-by-state approach, which has left the best regulator in the world, the FDA, on the sidelines of cannabis safety and use. That’s crazy.”

In Canada, there are medical and recreational paths and that can sometimes present conflicts as well.

“Australia has federal control for medicinal use, and recreational use is banned with little likelihood of it being lifted. It’s very cut-and-dried here. I think that gives us a massive advantage in sceptical markets such as South East Asia and Europe for being their preferred supplier of medically validated, quality medicinal cannabis down the track.”

Supporting clinical confidence

However, Australian doctors need to feel that same level of confidence.

“Clinicians are trained in new drug classes all the time and just because it has the word cannabis in it, we shouldn’t be scared of this class of drug either. We have to look at it scientifically and medically, he said.

“I support any clinician who has studied the data on medicinal cannabis and decides to say to their patient, this is not for you because… But no clinician should say to a patient this is not for you because I know nothing about it. That’s malpractice. If you don’t know, refer to someone who does.”

 “Clinicians are very good in Australia and are generally fast to adopt new medical techniques. Once they get over the stigma of cannabis and look at the decent data and the side-effect profiles, it will be a useful drug to prescribe,” Stewart said.