By Professor David Hunter, Florance and Cope Chair of Rheumatology and Professor of Medicine, University of Sydney and Royal North Shore Hospital

Australians living with arthritis pain are parting with thousands of dollars, sometimes tens of thousands, for unproven stem cell treatments that are no better off than injecting saline. 

It’s been documented that up to 60 practitioners have promoted unproven stem cell therapies in Australia[1], with many of the treatments on offer considered experimental.

Recently I have been seeing a growing number of patients come to me to enrol in the SCUlpTOR trial that I am leading, disappointed they’ve wasted their money on treatments elsewhere – locally and abroad. 

These providers are essentially snake oil salesman. They’re preying on people whose problems haven’t been solved by current medicines, offering hope but delivering no benefit. It’s very worrying. 

Do stem cells work?

Until recently, what they’re doing has been considered medical practice rather than using a therapeutic good, and because they’re using autologous stem cells, which are cells that are taken from the patient and then injected back in, it was not regulated by the Therapeutic Goods Administration (TGA). 

Practitioners providing stem cell or platelet-rich plasma (PRP) therapy for treating osteoarthritis might be able to demonstrate small scale before-and-after anecdotal evidence of efficacy, but there are no good-quality, placebo-controlled trials published in the medical literature supporting their practice and no conclusive evidence from clinical trials that any of these procedures work. As such, no therapeutic guidelines support this practice.

In fact, a trial that I recently conducted into PRP found there was no greater improvement in pain compared to those receiving placebo injections.

Despite this, clinics have popped up across the country offering treatments for a multitude of conditions, including osteoarthritis and various other joint problems, migraines, autism, and MS. While recent reforms introduced by TGA have been designed to ban advertising of unproven stem cell treatments, many clinics are still operating.

There’s clearly an inherent conflict of interest for these practitioners as the treatments are very lucrative. Platelet-rich plasma injections cost upwards of $300 per injection, and you often need 3-4 per area) or upward of $5,000 per stem cell injection. It’s good business for them; they’re exploiting vulnerable people at great cost and potentially at great risk.

Clinical validation is required

To properly explore whether stem cells work in osteoarthritis, I am leading the SCUlpTOR trial – a 440-person trialinvestigation into the potential modification of osteoarthritis using Cynata’s mesenchymal stem cells (MSCs) in people over 40 with osteoarthritis (OA) in their knees, and who have lived with moderate plus pain for several years.

It’s a gold-standard study: a randomised, double-blind, placebo controlled clinical trial designed to discover whether or not stem cell injections into the knee improve symptoms and slow disease progression to improve underlying disease and, therefore quality of life. 

Put simply, if it works, it could be a “cure” for osteoarthritis. And if it doesn’t, we’ll know that. 

The trial is currently open for recruitment in Sydney and Hobart and unlike what’s for sale on the market, there is no cost to patients as there shouldn’t be for participation in a clinical trial. 

Until these results are available and can prove that stem cell treatment is safe and effective for osteoarthritis, people should save their money and consider other proven treatments like weight loss and exercise. 

[1] Munsie et al 2017 Regen Med doi 10.2217/rme-2017-0070 

Professor David Hunter, Florance and Cope Chair of Rheumatology and Professor of Medicine, University of Sydney and Royal North Shore Hospital sat down with Dr Norman Swan to discuss the need for the SCUlpTOR trial to prove whether or not stem cell injections into the knee improve osteoarthritis symptoms and slow disease progression. And how some Australians are spending thousands of dollars on unproven therapies. 

Listen to the interview here: https://www.abc.net.au/radionational/programs/healthreport/arthritis-stem-cells-alzheimers-women-spider-venom-diabetes/101921202

Following her interview earlier in the year, Dr Jolanta Airey, Cynata CMO spoke to Stockhead about the chances of phase 3 clinical trial success, and Cynata’s own osteoarthritis trial. 

Read the story here: https://stockhead.com.au/health/the-chances-of-phase-3-success-and-the-asx-health-stocks-that-are-close-a-home-run/

In late January, Cynata received regulatory approval for commencement of its phase 2 clinical trial in acute graft-versus-host disease (aGVHD). It mostly affects women, and nothing has yet been established as an optimal second line therapy for either acute or chronic GvHD. 

However, mesenchymal stromal cells (MSCs), those which Cynata manufactures, have shown substantial promise. Read the news here: 

https://themarketherald.com.au/cynata-therapeutics-asxcyp-receives-approval-for-acute-graft-versus-host-disease-clinical-trial-2023-01-30/

For biotech investors, the news of approval of a new clinical trial by a regulatory body such as the FDA is a genuinely exciting milestone. But what many might not be aware of are the multiple steps involved in actually commencing a trial after the appropriate regulatory agency has given approval.  

This can lead to investor frustration and the misconception that perhaps things aren’t running smoothly when in reality, for complex, multicentre multinational trials to open all sites for enrolment, it can take up to twelve months post-approval. 

Here’s a topline summary of the steps that most biotechs and pharmaceutical companies will need to sequentially work through before recruitment of patients can begin. 

1. Development of core study documents such as final study protocol, Investigator’s Brochure (a collection of clinical and non-clinical data about the investigational product), and Informed Consent Form (a document volunteer signs when they agree to participate in a clinical trial).
2. Selection of a Clinical Research Organisation (CRO), the specialist company that actually runs the clinical trial on behalf of the drug company. This involves several bid defence meetings where quotes are analysed, and contract negotiation. 
3. Clinical research site selection and feasibility (with potential sites often being in multiple countries), followed by site qualification visits at each site where more detailed assessments is conducted about the site personnel/equipment to ensure the site has adequate resources and patient population for successful study execution.
4. Negotiation of budgets at individual study sites 
5. Submission to local Regulatory Affairs (RA) and Ethics Committees (EC). These bodies review research proposals involving human participants to ensure they meet ethical standards and guidelines.
6. Answering questions/requests from RA/EC to obtain approvals. Questions can range from pre-clinical package to risk/benefit assessments and further requests may involve conducting additional experiments.  
7. Submissions to the Research Governance Office (RGO) at each site and further negotiations on study documents, and site budget. The Research Governance Office is the office within the hospital that administers the processes used by the institution to ensure that it is accountable for the research conducted under its auspices. To be properly governed, research must be conducted according to established ethical principles, guidelines for responsible research conduct, relevant legislation and regulations and institutional policy. This step alone can take up to six months. 
8. Preparation of study plans including but not limited to: 
   • IP = Investigational Product manual
   • PVG = Pharmacovigilance plan (how to assess and report serious adverse reactions)
   • MMP = medical monitoring plan (the plan ensuring safety oversight and reviewing the protocol (e.g., study halting rules) and information about the study as it becomes available)
   • Lab manual
   • Clinical monitoring plan
   • Statistical Analyses plan
   • DM = data management plan etc.
9. Build and validate the electronic data capture (EDC) database to be used to record all the data from the subjects in the trial
10. Conduct Site Initiation visits at each site which involves training the site study team on study protocol, adverse event reporting data recording in EDC and other systems to be used during the study. 

As you can see, it’s not a short nor simple process. And, within this process, some of the steps may take multiple iterations even if appropriately undertaken. 

I appreciate that it’s difficult for already patient investors to continue to be patient but at the end of the day, designing good clinical trial strategies to ensure they have the best chance of reaching the intended end point and move to commercialization is imperative.