After four months in the doldrums due to its COVID-19 treatment in severely ill patients missing the mark, Melbourne-based biotech Mesoblast (ASX: MSB) is now pinning its hopes on fresh results that showed reduced mortality for under 65s.
Mesoblast was dealt a blow in December when a US trial failed to meet its 30-day goal of a 43 per cent reduction in mortality for patients suffering from severe acute respiratory distress syndrome (ARDS) due to COVID-19 infection, cutting enrolments short for the study as well as the group's share price.
But the company founded and led by Dr Silviu Itescu pressed on with its 222 enrolled patients, and today revealed age could be a determining factor for the success of its stem cell treatment remestemcel-L.
Today's results demonstrate a 46 per cent reduction in mortality for patients aged under 65 who are treated with remestemcel-L, but not for those aged 65 and older.
When combined with the corticosteroid dexamethasone which has become part of standard care for critically ill COVID-19 patients on mechanical ventilation, Remestemcel-L was found to reduce mortality by 75 per cent in the under 65 demographic.
"Reduction in mortality in mechanically ventilated patients under 65 years old remains a critical unmet need since as many as 72 per cent of currently hospitalised patients across the US with COVID-19 are in this age category," says Itescu.
"This is similar to other causes of viral ARDS such as influenza where 70-80 per cent of patients in intensive care units are under 65.
"The reduction in mortality seen with remestemcel-L in this age group highlights the potential to make a meaningful difference in the treatment of diseases of excessive inflammation."
Itescu emphasises the complementary effects of Mesoblast's treatment with dexamethasone are particularly noteworthy, acting to target the inflammatory cytokine process driven by inflammatory macrophages and T-cells.
"Mechanistically, there is an understanding of synergy between the two. That probably in part explains why we've seen such exciting results in mortality reduction," he says.
Mesoblast's experts have formed the view that the negative third interim analysis that set back it plans may have resulted from a progressively ageing cohort of patients with more co-morbidities, whose median age rose from 59 in the first half to 67 in the second half.
The company believes a different dosing regimen might be needed to achieve mortality reduction in patients aged over 65 with co-morbidities.
"The mortality benefit observed with remestemcel-L in ventilator-dependent patients younger than 65, particularly in combination with dexamethasone, has the potential to change the treatment regimen in this critical patient population," says Mesoblast chief medical officer Dr Fred Grossman.
"As cases continue to surge in younger patients across the US, we plan to meet with the FDA to discuss next steps in the regulatory process."
Itescu says if remestemcel-L were to be approved for emergency use, Mesoblast still has a commercial agreement in place with Swiss pharmaceutical giant Novartis.
"We have plans for a factory scale-up, we have proprietary media that contains recombinant cytokines that enables substantial yield improvement, and potentially we could move from two-dimensional to three-dimensional bioreactor production," he says.
"We are preparing ahead of the curve, should we be in a position to launch such a product, particularly in the US."
He says vaccine roll-outs in places can be very effective, reducing new cases by as much as potentially 80 per cent, but that still leaves room for treatments like remestemcel-L should it be given the green light.
"Nonetheless, the continued emergence of variants, particularly from third world countries, the continued social interactions particularly in younger people who in the northern summer now will be outdoors and enjoying life I think means there will be continued endemic cases of this virus in various pockets," he explains.
"There will be continued surges, resurgences, etcetera and there will be a steady state of patients who will need ICU care, mechanical ventilation, and treatments for the worst outcomes and the highest mortality risks of COVID-19 - ARDS.
"We clearly see this as a potential therapeutic for the steady state, even in the setting of large numbers of patients being vaccinated.
"Even if an 80 per cent reduction in infectivity is a success through vaccination, that still will result in a large number of potential fatalities that could be prevented by the use of remestemcel-L, together with dexomethasone."
Updated at 10:04am AEST on 30 April 2021.
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