The Mesoblast limited (ASX: MSB) share price has had an incredibly eventful year.
The stem cell-focused biotech company's shares have been as high as $5.70 and as low as $1.02.
Today, the Mesoblast share price sits at $2.40 after crashing over 40% lower last week.
What is happening with the Mesoblast share price?
Mesoblast has been extremely busy this year with a number of key trials and applications.
This includes running a trial for remestemcel-L in the treatment of COVID-19 Acute Respiratory Distress Syndrome (ARDS), an application for remestemcel-L to treat paediatric patients with steroid-refractory acute graft versus host disease (SR-aGvHD), and a trial of rexlemestrocel-L in patients with advanced chronic heart failure.
Unfortunately, after so much promise, the company has fallen short on each occasion.
Advanced chronic heart failure.
Last week Mesoblast released the top-line results from the landmark DREAM-HF Phase 3 randomised controlled trial. This was a trial of its allogeneic cell therapy rexlemestrocel-L (REVASCOR) in 537 patients with advanced chronic heart failure.
Rexlemestrocel-L is a therapy that was being developed with Teva Pharmaceutical Industries until 2016, when the pharma giant walked away from the project due to weak data.
While the DREAM-HF trial showed a reduction in the incidence of heart attacks or strokes, there was no reduction in recurrent non-fatal decompensated heart failure events. This was the trial's primary endpoint.
Remestemcel-L for paediatric SR-aGvHD.
In October the Mesoblast share price crashed lower after the US Food and Drug Administration (FDA) decided not to approve its remestemcel-L therapy for the treatment of paediatric patients with SR-aGvHD.
Instead, the FDA has requested that Mesoblast undertake at least one additional randomised, controlled study in adults and/or children. This is to provide further evidence of the effectiveness of remestemcel-L for SR-aGVHD.
Remestemcel-L for COVID-19 ARDS.
The icing on the cake for Mesoblast was last week's announcement that its randomised controlled trial of remestemcel-L in ventilator-dependent patients with moderate to severe ARDS due to COVID-19 infection was a failure.
That announcement revealed that the Data Safety Monitoring Board (DSMB) has performed a third interim analysis on the trial's first 180 patients.
And while the DSMB has reported that there were no safety concerns, importantly, it noted that the trial is unlikely to meet its 30-day mortality reduction endpoint at the planned 300 patient enrolment. In light of this, the DSMB effectively ended the trial early by instructing Mesoblast to recruit no further patients.
The company has suggested that changes in the treatment regimens for COVID-19 patients are to blame for the trial's failure.
It explained: "During the course of the trial, as the pandemic has evolved, numerous changes in the treatment regimens for COVID-19 patients occurred, including both prior to and while on mechanical ventilation that may have an effect on the mortality endpoint in the trial."
This trial data has now called into question the company's deal with pharma giant Novartis that was potentially worth ~US$1.2 billion.
That agreement had an initial focus on the development of a treatment for ARDS, including that associated with COVID-19. Whether this focus still has a future, the two companies will no doubt have to work out in the coming weeks and months.
