Mesoblast spins a PhIII cell therapy miss in heart failure as a...

Mesoblast spins a PhIII cell therapy miss in heart failure as a win, highlighting positive mortality data

https://endpts.com/mesoblast-spins-a-phiii-cell-therapy-miss-in-heart-failure-as-a-win-highlighting-positive-mortality-data/

About two and a half months after the FDA turned away their lead program, Mesoblast $MESO reported a Phase III miss Monday afternoon for their second clinical product. But the Australian biotech pointed toward data in a secondary endpoint it thinks the agency might find promising.

In a late-stage trial measuring rexlemestrocel-L in 537 patients, Mesoblast found that the experimental cell therapy did not significantly reduce hospitalizations over placebo in individuals with recurring heart failure. The program managed to hit secondaries in mortality-rate reduction for earlier stages of heart failure, and it’s here where Mesoblast hopes it can still pave a path toward accelerated approval should regulators prove receptive.

“The hospitalizations in patients with chronic heart failure are really about their ability to handle volume loads and patients who are brittle are not able to handle volume loads very well,” CEO Silviu Itescu said in a conference call Monday evening. “It appears that our therapy does not have any impact on those types of outcomes.”

Investors appeared skeptical of Mesoblast’s claims as the company’s shares fell after the bell Monday and continued to slide Tuesday morning to down about 17%.

The Phase III trial randomized patients evenly into the drug or placebo arms. Mesoblast enrolled 206 patients with Class II heart failure and 331 individuals who had progressed to Class III, a more severe form of the condition. In order to be included in the study, all patients needed to have been hospitalized for heart failure within nine months of starting treatment.

Mesoblast did not report any numbers or a p-value for the primary endpoint, only saying there was “no reduction” over placebo in hospitalizations for recurring non-fatal heart failure events.

Instead, the company revealed its positive secondary endpoint data. In all patients, rexlemestrocel-L showed a 60% reduction in heart attacks and stroke related to cardiac death, Mesoblast said, scoring a p-value of 0.002. The therapy also demonstrated a 60% reduction in death from any cause in the Class II population, good for a p-value of 0.037.

Rexlemestrocel-L also prevented such patients from progressing to severe disease but did not specify any numbers, the company said, only reporting a p-value of 0.004. Those in the control arm with maximum standard of care therapy progressed from Class II to Class III after an average of 20 months.

It’s these data where Mesoblast now sees a potential path ahead. Itescu further told investors in Monday’s call that rexlemestrocel-L could prove a complementary medicine to drugs that reduce hospitalizations but don’t reduce mortality. He also said in previous meetings with the FDA that the agency has made clear it is focusing on mortality, despite hospitalization serving as primary.

When the company started its trial, Itescu said, the theory for the underlying mechanism was that the medicine could reduce inflammation in heart muscles, protect tissue from dying and prevent those muscles from becoming scar tissue.

“The question then goes to why do we have this major benefit on mortality?” Itescu said on the call. “I think the data that we’ve seen here, where we’ve seen this dramatic reduction in mortality in patients who are at an advanced stage of disease but not yet so advanced that they’re not able to be rescued, suggests that this mechanism may be playing a key role.”

Itescu also noted the program’s benefits in less severe cases of heart failure, saying it could potentially be used to intervene before patients progress past Class II. The key moving forward will be meeting with regulators and figuring out exactly the right time to dose patients.

Monday’s results follow the FDA handing Mesoblast a CRL for its acute graft-versus-host disease program, remestemcel-L, back in October. Regulators objected to the nature of the data package, with the company hoping to gain approval on the basis of only a single, open-label trial. Despite the rejection, Novartis partnered with the biotech last month in a $1.2 billion-plus deal, hoping to develop the candidate for ARDS, including cases related to Covid-19.