Mesoblast faces FDA pushback over cell therapy manufacturing, clinical data: documents

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Mesoblast's Ryoncil is scheduled for a full FDA review in September, but first it will face an advisory committee's questions. (Getty)

The FDA in recent years has been tough on cell and gene therapy makers, particularly when its comes to approving the labor-intensive and complicated manufacturing process. The agency now has its eyes set on Mesoblast's cell therapy candidate—and an early review doesn't look positive.

An FDA advisory committee on Thursday will question Mesoblast's ability to consistently manufacture effective doses of its Ryoncil (remestemcel-L), an investigational cell therapy for pediatric acute graft vs. host disease (GVHD), according to briefing documents posted online.

In those documents, the FDA argued that Mesoblast's pivotal phase 3 data for Ryoncil did not demonstrate that the therapy's proposed mechanism of action was actually linked to positive clinical outcomes. Ryoncil is composed of culture-expanded mesenchymal stromal cells (MSCs) that Mesoblast links to the reduction of pathogenic inflammation in GVHD patients.

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"While (Ryoncil) and other MSC-based investigational products have demonstrated apparent immunomodulatory effects in in vitro experiments, the ability of (Ryoncil) to reduce inflammation as measured by inflammatory biomarkers in humans receiving the product has not been demonstrated," the FDA said. 

Moreover, the FDA questioned Mesoblast's manufacturing of the therapy, saying other MSC-based therapies show "significant functional heterogeneity" between patients and that the biotech's expansion of MSCs in culture through donor banks could dilute doses over time. 

Ryoncil is scheduled for a full FDA review Sept. 30. While advisory committee votes are non-binding, the FDA often follows its committees' opinions.  

A Mesoblast spokeswoman could not be reached for comment by press time. 

RELATED: Mesoblast preps first filings for GVHD drug after phase 3 win

Mesoblast is only the latest cell or gene therapy maker to potentially run into roadblocks with the FDA over its manufacturing, a notoriously expensive and labor-intensive process.

On the heels of the FDA posting its briefing documents online, Mesoblast's share price dropped from $17.42 at Monday's close to a low of $10.93 on Tuesday—an indication that investors aren't psyched about Ryoncil's chances.

In February 2018, Mesoblast posted pivotal phase 3 data in pediatric GVHD showing 69% of Ryoncil patients had a complete or partial response to the treatment after 28 days. The therapy is already approved as Temcell in Japan, where it is licensed to JCR Pharma. 

Mesoblast is also pursuing clinical trials for Ryoncil in adult and chronic GVHD and to treat acute respiratory distress syndrome in COVID-19 patients, among other indications.

RELATED: Mesoblast defends stem cell therapy for heart failure after trial miss

In November 2018, Mesoblast took another share price hit from investors after its stem-cell therapy Revascor (rexlemestrocel) flopped a phase 2 study weaning heart failure patients off a left ventricular assistance device. 

Despite the miss, Mesoblast defended the results, saying that Ryoncil did allow a subgroup of patients with ischemic heart failure to be weaned off the devices temporarily. The biotech also noted there was a significant 76% reduction in major gastrointestinal bleeds plus a 65% drop in bleed-related hospitalizations in patients treated with the therapy.

The biotech's CEO, Silviu Itescu, argued that the results had been "misunderstood by the market" and that the study set up a “pathway for potential regulatory approval." 

According to the company's pipeline, Revascor in phase 3 trials for late-stage heart failure patients.

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