Clinics and data-backed medicinal cannabis firm Emyria has embarked on a drug-development program of its own. Here, chief executive Dr Michael Winlo tells Cannabiz that TGA registration must be the ambition for producers, and suggests why some may be unwilling to invest in research.
Developing and registering its own drugs was not part of Emyria’s business plan.
Its pre-IPO prospectus, released last February under its previous name, Emerald Clinics, spoke of “drug-development customers”. Absent was the proposal to get into the drug development game itself.
Yet in the second half of 2021, the WA-based firm will lodge a final evidence package to the Therapeutic Goods Administration to support registration of EMD-003, its own cannabinoid medicine to tackle anxiety, depression and stress.
Initial clinical evidence analysis and patent filing has already been completed, with clinical trials expected to begin in the first six months of the year.
For Emyria, the home-grown drug development program emerged from the reluctance of medicinal cannabis producers to partner with the firm’s analytical arm.
The company’s directors hoped its mass of real-world clinical data, gathered from patients at its five Australian clinics, would be an attractive proposition for drug developers keen to seek registration for their product by building an extensive body of evidence.
But while Zelira Therapeutics and Canopy Growth have seen the possibilities and are working with Emyria – on autism and insomnia projects in the case of Zelira – few others, so far, have signed up.
“Our model was to build the evidence and we thought people would purchase that data, pay subscriptions and work with us to try to get their drugs registered,” chief executive Dr Michael Winlo said. “But with a couple of exceptions, it’s taking a little time. And in the absence of that interest, to be frank, we’ve decided to do it ourselves.”
Dr Winlo, the former CEO of a clinical trial unit in Perth, told Cannabiz the company expected producers to “mature in their thinking”, to understand they are operating in a highly competitive environment and to plot a course for drug registration.
Until there is evidence supporting formal drug registration, medicinal cannabis “will never be breakthrough mainstream medicines able to help millions of people”, he said.
“Our expectation was that producers would take a more traditional view of these medicines.
“We were hoping to partner with producers so they could bring us their treatment and we’d say where it might work. We could give advice, consult and help develop treatments. For us it was about the data and the clinical evidence we were gathering and what that means.
“We’ve got this great opportunity to try these medicines on people who want to take it, and where nothing else is working. But people are fumbling this terrific opportunity to learn from these experiences with real patients. So we invested heavily in data systems and have brought all sorts of clinical trial discipline to how we operate our clinics so we can optimise the quality and utility of the clinical evidence we gather.”
So, Zelira and Canopy aside, why has take-up been subdued?
A number of factors have contributed to the slow response, said Dr Winlo.
With several producers operating in a listed environment, and subject to the associated market scrutiny, he believes the delivery of frequent, positive news to demonstrate continued growth and progress has taken priority.
Additionally, few producers have pharma backgrounds, he says, and regard growth as a marketing challenge, to be achieved by “twisting the arm of GPs and working the patient advocacy angle”.
“They’ve been making a lot of noise on that side and, frankly, it’s kind of irritating mainstream medicine,” Dr Winlo said. “We get gripes from doctors who have been told from 15 different producers that their drugs are great, but who have not been able to back it up with evidence.
“Embarking on a trial to get registered is an expensive proposition… so from a return on investment angle, it’s probably more powerful for listed companies to hire more sales reps and get the number of scripts from 100 to 700 in six months rather than take a long-term punt and spend a million dollars or more to run a pivotal clinical trial.
“Another problem is they realise, somewhat fundamentally, that they’re generic medications. So the first one to move, to make a claim and tell the world their CBD drug works for ABC, you’re going to get a lot of fast followers jumping on the back of that news.
“There is an argument to say that maybe regulators need to think of ways of rewarding first movers who make that investment for registration, to give them exclusivity on an indication, at least for a while.”
There can be little doubt that individual manufacturers, and the industry as a whole, are making solid progress.
Product sales have shown dramatic growth over the past 12-18 months, while the overall number of prescriptions approved under the Special Access Scheme in 2020 climbed to almost 60,000.
Nevertheless, positive as that figure may be, it is dwarfed by the jaw-dropping volume of more traditional medicine dished out to patients.
According to Dr Winlo, 29 million prescriptions are written for antidepressants in Australia in a 12-month period. Not far behind are analgesics, with 23 million prescriptions.
Furthermore, the government subsidises Pregabalin to the tune of $138m. As an unregistered medication, patients taking medicinal cannabis receive nothing in state support.
“The 60,000 SAS-B scripts is a remarkable number from where it was a year ago, so on a percentage growth measure, it’s exponential,” Dr Winlo said. “But it’s still a small number when you look at antidepressants and analgesics.”
Further impacting the original Emyria strategy to form partnerships was the rapid rise of clinic networks across Australia, many opened and owned by producers.
Dr Winlo conceded Emyria was surprised at such a development.
“We didn’t expect some of them to just go off and start their own clinics,” he said.
That manufacturer/clinic relationship sits uncomfortably with some in the industry – Dr Winlo included – amid the ethical concerns of being both manufacturer and prescriber.
He revealed that Emyria’s clinics have been offered what he labelled “kickbacks” for writing prescriptions for certain products.
“You think, hang on a second, you’re not allowed to do that,” he told Cannabiz. “We’d be then told, ‘oh, just call it a coupon or give the money to the patient’. Well, no, we’ll do a research program with you.
“We don’t take kickbacks from any producer and pride ourselves on being ethical and independent. With our own drug development, any of those drugs that get registered will not appear on our formulary. Our doctors will not prescribe our own products. We believe that is really important.
“When we decided to do our own drug development, we had to think long and hard. Did we really want to be a clinic and become a drug company? We had to think through some of the ethics around that.
“But we are specialising in unregistered treatments. We are only for patients where nothing else is working. So if we can help bring a registered drug to market we can advise patients who might benefit from that registered treatment to get it from their regular doctor. There would be no need for them to go through the experimentation process with us.
“We could then take the next group of patients, for whom nothing else is working, and continue to grow through that.
“We’re trying to get the best outcome for patients and learn about what’s going on as we go. We can look at a disease group or a cohort in aggregate after some months with us and… use those insights to inform where we target our drug development. We can say with more confidence than usual that this dose will work for this patient and likely to give this result over this period of time.”
These insights can then be followed by randomised controlled trials – without which sceptics will never be convinced – which can be designed, led and informed by the evidence already collected, he said.
Dr Winlo said data collected and analysed by Emyria demonstrated efficacy even at 60mg per day, the maximum daily dose contained in the TGA’s interim decision on the down scheduling of low-dose CBD. That was increased to 150mg in the final ruling last month following consultation with industry bodies which doubted the value of a 60mg dose.
While accepting 150mg is likely to be more efficacious, Dr Winlo said Emyria was “pretty confident we could do something interesting” at the lower amount.
“The lack of evidence is really a product of research that hasn’t been done,” Dr Winlo said. “It’s a case of poorly controlled studies which hadn’t been followed up. The research has been patchy and incomplete.
“In the patients we were seeing, there were signals. It wasn’t 100% working for everybody, but you could certainly define a cohort where there were significant improvements, even at lower doses.”
While the ability to potentially access low-dose CBD through pharmacies without a prescription has been welcomed, Dr Winlo highlighted one stark reality: robust evidence will still be required for registration.
“You still need product-specific evidence of efficacy and safety for a particular indication for a particular dose,” he said. “That’s going to require RCT. It requires an investment of some kind and we can offer some of those insights.”
For Emyria, achieving drug registration will open a major new revenue stream. As Dr Winlo put it, registration will be a “big milestone that will essentially translate into sales”.
“We’ll be trying to do everything we can to make that happen as quickly as possible.
“We’ve come to a point where we’ve now hit critical mass, with about 3,000 patients. We’ve had many of them followed up for a year. We’ve got incredible data, really meaningful results. And I feel very confident we can take those insights to drugs and get them registered quickly.”