- A trial testing Mesoblast's (MSB) remestemcel-L treatment in ventilated COVID-19 patients has ceased enrolment early as valid data can't be obtained
- Only 223 of the planned 300 patients have been treated, but the trial won't proceed as planned as primary endpoint data would be invalid
- The trial was targeting a "43 per cent reduction in mortality at 30 days for treatment with remestemcel-L on top of maximal care"
- But "maximal care" has evolved and patients aren't receiving the same treatments across the board, diluting the clinical rigour of the study
- The Data Safety Monitoring Board has recommended the trial's secondary endpoints still be followed up
- Those outcomes relate largely to the suppression of the body's runaway immune response, which is the leading cause of death in COVID-19 patients
- Mesoblast will still analyse data to guide decisions on a development program for remestemcel-L
- Mesoblast is trading 36.61 per cent lower for $2.39
A trial testing Mesoblast's (MSB) remestemcel-L treatment in ventilated COVID-19 patients has ceased enrolment early as valid data can't be obtained.
Only 223 of the planned 300 patients have been treated. Those patients will all have full follow-up, but the Data Safety Monitoring Board (DSMB) has noted the trial was unlikely to "meet the 30-day mortality reduction endpoint" as treatment regimens since the study was planned have changed, skewing the trial's outcomes.
While any trial being called off early is essentially bad news, that's not exactly the case here. The trial is only being halted because valid data can't be gathered in an objective and clinically rigorous way.
Patients have received various therapies both before and during their time on ventilators which will have an effect on the outcomes of their treatments.
This dilution of the pure effects of remestemcel-L has made any data gathering essentially invalid for the trial's primary endpoint, which aimed for a "43 per cent reduction in mortality at 30 days for treatment with remestemcel-L on top of
The fact COVID-19 "maximal care" treatments have evolved so much since the pilot data was gathered have made that endpoint unattainable, as a lack of consistent treatment regimes across the patient cohort obscure the effects of Mesoblast's therapy.
Essentially, it would be impossible to tell what proportion of any reduction in deaths could be attributed to remestemcel-L, so the study can't be assessed to appropriate clinical standards.
The DSMB has recommended the trial's secondary endpoints — including days alive off mechanical ventilation at 60 days post randomisation, overall survival, days in intensive care, duration of hospitalisation, and cardiac, neurological, and pulmonary organ damage — still be followed up.
Remestemcel-L acts to suppress a damaging, runaway immune response in patients known as a cytokine storm. It is this effect which causes Acute Respiratory Distress Syndrome (ARDS) — the leading cause of death associated with COVID-19.
By diminishing this inflammatory response, it's believed patients will have significantly better outcomes, both in terms of short-term mortality rates, and longer-lasting effects related to tissue and organ damage.
The follow-up recommended by the DSMB includes monitoring for circulating cytokines and inflammatory markers, so at least some valuable data on MSB's therapy may still be attained regarding the suppression of ARDS.
The other secondary endpoints will also be analysed to identify any clinical outcomes that may guide decisions on a development program for remestemcel-L in non-COVID ARDS.
While the premature end of the COVID-19 trial may not be great news for MSB, there's still hope the company can prove the worth of its therapy in treating the effects of ARDS.
Mesoblast is trading 36.61 per cent lower for $2.39 at 10:29 am AEDT.