Are we mortgaging the future as COVID-19 closes clinical trials?

The COVID-19 pandemic has led to 527 clinical trials being shut down in Australia and New Zealand the last two months, up 36 per cent on the prior two months as many organisations deem the patient risk of exposure to be too high.

Globally, 10,174 clinical trials registered with the US government site ClinicalTrials.com were suspended, terminated, withdrawn or moved to ‘not recruiting’ status in March and April as the pandemic accelerated, a sharp 41 per cent jump on the previous two months.

Postponements and delays to clinical trials are likely to have ramifications for many years, blowing out the cost of testing a drug or device for cash-strapped biotechs, removing a cohort of potential participants, and delaying therapies in favour of coronavirus-related drug candidates.

A key risk, says one biotech CEO, is delays today will affect the drugs available in the future, so there needs to be a degree of caution about mortgaging the future for the sake of the present.

But like with telehealth, it has also forced on the industry a rapid switch to digital methods in order to keep open trials that are running now.

Australia is recognised alongside the US and Europe as one of the world’s three key clinical trial hubs, after years of incentives such as a generous R&D tax rebate helped to establish the expertise, corporate infrastructure, and regulatory reputation, making any hit to the industry all the more painful.

Last one out, turn the lights off

With the cost of clinical trials running into the multi-millions, recruitment delays will take their toll on pre-revenue biotechs, and their shareholders.

Companies from stem cell company Cynata (ASX:CYP) and Alzheimer’s hopeful Actinogen (ASX:ACW) have delayed the start of new trials and are putting on hold current ones.

Exopharm (ASX:EX1) has seen a phase one stem cell wound healing study disrupted half way. It won’t be able to recruit enough people and is preparing to fill data gaps with a supplementary study.

Emvision (ASX:EMV) has paused new patient enrolment in a medical imaging study, while Medlab Clinical (ASX:MDC) closed a depression study early with 120 people recruited rather than 150.

Medlab CEO Sean Hall says a lot of companies will be coming back to the market asking for more money to keep a trial afloat.

“A number of biotechs that don’t have a revenue stream will struggle to keep the lights on,” he told Stockhead.

Lobby group AusBiotech has been vocal on this subject, saying biotechs employ more than 65,000 people, yet 86 per cent of the sector are in the pre-revenue start-up or SME category so are excluded from the government’s JobKeeper $1500 wage subsidy, which requires companies to see a COVID-19 induced 30 per cent revenue drop to be eligible.

AusBiotech is seeking a ruling from the Tax Commissioner on the issue.

Another option that has been mooted is to bring forward the R&D tax refund.

Mortgaging the future

It will take time for the long-term impact of trial stoppages to be seen.

The biotech sector is reducing the number of early stage clinical trials and not starting new ones, which will affect the drug discovery pipeline, says Medicines Australia chief Elizabeth de Somer.

If promising discoveries with intellectual property don’t progress to human trials, that will change the availability of promising studies in later stage trials.

“The early discovery phase is as important as later stage development,” she told Stockhead.

Further, the knock-on health impact of people not going to their doctors, be it from fear of police retribution or contagion, will affect the pipeline of people available for clinical trials later.

de Somer says people whose illness is at a stage that could be treated in a clinical trial in the near-to-medium future, may not be eligible if a study is delayed and their illness progresses.

A more positive outcome could be harmonised regulation between states around clinical trials.

“This is an opportunity for the commitments to a harmonised regulatory streamlined process for clinical trials to be front and centre. We want to minimise the barriers to conducting clinical trials and this is an ideal opportunity to look at those,” de Somer said.

The new rules

Although the global ramp up in COVID-19 infections began in earnest in March, most trial shut downs took place in April when regulators began to issue directives on how to manage patient care during a public health crisis.

The US Food and Drug Administration (FDA) was the first, issuing guidance in late March which has since been updated, and Australia’s Department of Health put out its own, which is largely similar to the US version, just before Easter.

The Australian guidance says the wellbeing of patients is paramount and that might mean stopping a trial, or continuing it if a pause or cancellation would put lives at risk.

In a 10-page document the Department of Health outlined contingency planning, such as whether a hospital or trial centre could handle a study if participants took up beds and medical staff’s time that may be needed by COVID-19 patients, and using remote monitoring where possible.

What it’ll take to get a study off the ground

In practice the regulatory advice means organisations like the Clinical Trial Support Office of the University of Sydney have said newly approved trials shouldn’t launch.

James Garner, the chief of brain cancer hopeful Kazia Therapeutics (ASX:KZA), says “life and death” treatments will see trials go ahead with modifications, because the usual standard of care is either limited or non-existent.

“They need to be cared for in some way. The area we work in, glioblastoma, a patient diagnosed has about a 12-13 month life expectancy. Those patients realistically can’t be told to go home and come back in six months,” he told Stockhead.

Other illnesses such as hypertension, which can be controlled with commonly available drugs, or restless leg syndrome are likely to be delayed.

Furthermore, many companies are prioritising COVID-19 or respiratory treatments.

Telemedicine is saving some trials, as remote monitoring devices and Zoom calls keep patients and researchers up to date, and building off an MTP Connect pilot for regional and rural access to clinical trials has been in play since 2017.

“[Biotechs] have looked at innovative ways of engaging with patients remotely, using remote monitoring of data, posting medicines out to patients, anything that minimises that face-to-face contact,” de Somer said.

“I think [the pandemic has] accelerated some of those changes.”