Devil in the detail – here’s how advanced-stage clinical trials are actually built
Health & Biotech
Health & Biotech
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Most biotech investors are familiar with the concept of clinical trials, where drug applications are tested first for safety and then for effectiveness.
But at the ground level, there’s a lot more to it than that. And to break down the details, Stockhead caught up recently with Dimerix (ASX:DXB) CEO Dr Nina Webster for an in-depth analysis of how the process really works.
Dimerix is moving towards Phase 3 clinical trials for its DMX-200 drug in the treatment of FSGS – a rare kidney disease. So she’s well placed to highlight the amount of work that actually goes into a trial, and what information investors should be watching for. Read on below to find out.
Before a clinical study starts, it has to be designed and as Webster explains, that’s “not just a case of just sitting down for a day and then it’s written”.
The basics of protocol design relate to patient recruitment (e.g. age, gender), and testing parameters such as drug dosage levels and the timing and duration of each dose.
And each component of the design has to be built with the end goal in mind – to establish “statistically meaningful data to support marketing authorisation”, Webster says.
In other words, regulators have to be satisfied that the study will meet their approval criteria in the event of a successful trial
For a drug such as Dimerix’s FSGS treatment which has a global application, that meant protocol design had to take into account feedback from multiple regulators.
“So it takes a huge amount of work because every country has different requirements,” Webster said.
Earlier this month, Dimerix received study approval from the EMA (European Medicines Agency) and is currently holding discussions with the US FDA.
The next step is to finalise that protocol and lock in those endpoints based on their feedback and advice, Webster said.
“It’s critical to make sure we’ve built in any commentary from them, so when we go to study we’re confident the endpoint is approvable.”
When it comes to protocol design for clinical studies, patient recruitment is “often the biggest challenge”, Webster says.
Again, Dimerix’s study has some unique attributes in that context because its FSGS drug has been approved for orphan designation as a treatment for a rare disease.
“We’re the only company currently recruiting for a global Phase 3 trial in FSGS. That means we’re not competing for patients with other companies, which is really important,” Webster said.
But it also presents challenges, because the field of suitable patient applicants can shrink fast.
“With recruitment for a rare disease it’s harder to identify eligible patients, because you want to control the parameters of your study as much as you can,” Webster said.
For example, some patients may suit the base criteria but are also on multiple other medications, which make them ineligible.
“For every 40 patients we identify, there might be only one that’s actually eligible. So it’s a continual process to build capacity and develop different strategies for recruiting patients” Webster said.
Are you ready for your ‘randomised double-blind multi-centre placebo-controlled trial’?
Don’t panic – that’s the description of the DMX-200 FSGS study, and Webster is here to break it down.
‘Double blind’ means that neither the patient or physician will know what the patient is receiving, which is crucial to remove any bias from both the trial and the review process.
‘Multi-centre’ simply means the trial has been approved for multiple jurisdictions, e.g. both the US and Europe.
And ‘placebo-controlled’ provides a standardised way to test the effect on patients using the drug against those not using the drug.
“Generally speaking, the US requires placebo-controlled studies to approve the end-point, whereas in contrast Europe often requires a comparator study,” Webster said.
“But in our case it’s different because we’re trialling a treatment with orphan designation where nothing has been approved, so it’s the same standard of care for each of those territories,” Webster said.
Once the extensive planning is completed, the next step is the study itself. And to carry it out, biotech companies often seek partnerships with a contract research organisation (CRO).
“You want to engage with a CRO that’s capable and has experience in the space you’re working with,” Webster said.
In preparation for its US study, Dimerix recently appointed the NYSE-listed IQVIA Holdings as the lead CRO.
“The CRO has a good understanding of where your patients are; they are the groups with their feet on the ground in each country, and they manage those clinical sites as well,” Webster said.
While IQVIA will run the study, it’s still incumbent on the drug development company to obtain ethics approval in each country, and take responsibility for safety monitoring.
For biotech stocks, a successful clinical trial can make or break companies and send share prices rocketing higher (or plummeting).
But as Webster explained, if a treatment does break through the strenuous approval process, the drug still needs to get made – and that’s not a simple task either.
“There’s an assumption you can call the manufacturer and have it made tomorrow, but it doesn’t work like that,” she said.
Ordinarily, companies need to book their manufacturing slot 6-12 months in advance. They also need to confirm it meets GMP (good manufacturing practice) standards, then collect stability data to ensure the drug can maintain its form under different environmental factors.
“It’s a balancing act because you don’t want to commit too soon, and there’s usually penalties if you cancel a booking slot,” Webster said.
“But if you don’t book it, you don’t get the stability data and you can’t do the study.”
There’s also matters like label translation for each country, and regulatory signoff for each jurisdiction.
Weighing up the drug development process as a whole, Webster conjured up an image of the Sunday roast.
“My analogy is it’s a bit like cooking a roast dinner, because you have to put all these things in the oven and they’ve all got to come out at the same time,” she said.