Update: Since this story was published, the ODAC met and voted in favour of recommending Mesoblast's graft versus host disease (GvHD) treatment remestemcel-L. Click here for more.
Before pivoting to find a treatment for critically ill COVID-19 patients suffering from severe acute respiratory distress syndrome (ARDS), Mesoblast's (ASX: MSB, NASDAQ: MESO) most advanced business centred on an entirely different ailment.
The Melbourne-based company has sought US regulatory approval for its stem cell-based product remestemcel-L in treating graft versus host disease (GvHD) - a potentially life-threatening condition that some people experience after receiving a bone marrow transplant (BMT), often when treating blood cancer.
But the complex nature of cells and the variability between donors makes getting the green light much harder for stem cell-based products compared to other drugs.
The US Food and Drug Administration (FDA) has released a briefing document about remestemcel-L, which Mesoblast aims to market for children as 'Ryoncil', ahead of an Oncologic Drugs Advisory Committee (ODAC) meeting on 13 August.
After 20 years of development for remestemcel-L, the FDA has shown it is not satisfied with the biologics license application and there is still plenty more work that is needed.
MSB shares were down 26.49 per cent to $3.58 at 12:34pm AEST, while substantial holder M&G Investments Funds has wound back its stake by around one percentage point to just under 10 per cent of the stock on issue.
The FDA says while the product has shown apparent immunomodulatory effects in in vitro experiments, its ability to "reduce inflammation as measured by inflammatory biomarkers in humans receiving the product has not been demonstrated".
"A relationship between these in vitro lot release assays and the clinical effectiveness of the product has also not been demonstrated," the FDA says.
The FDA believes the critical quality attributes (CQA) of the therapy may not be sufficient to ensure the manufacturing process consistently produces remestemcel-L lots of acceptable quality.
"Characterisation of cell-based products in general is complicated by the complex nature of cells relative to other types of drugs, as well as heterogeneity among cells comprising the active ingredient," the FDA says.
"Defining product quality attributes that relate to the product's clinical effectiveness, therefore, may require more extensive product characterisation for cell therapy products than for other biological products."
Remestemcel-L is based on bone marrow aspirate taken from donors, and is a form of mesenchymal stromal cells (MSCs). The FDA notes this also brings limitations from a production standpoint.
"The first stage of the manufacturing process for remestemcel-L is the expansion of MSCs derived from a single allogeneic donor into an intermediate donor cell bank (DCB).
"Each DCB is then further expanded to create multiple lots of remestemcel-L DP [Drug Product].
"MSCs in culture cannot expand indefinitely and are reported to show a decrease in attributes related to MSC quality after extended expansion, therefore, new DCBs must be produced on a regular basis."
At 2:30pm AEST Mesoblast made an announcement to the ASX emphasising the ODAC provides advice and appropriate recommendations to the FDA based on potential issues highlighted by the FDA during their review.
"Although the FDA will consider the recommendation of the advisory committee, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding," Mesoblast stated, noting the product was under priority review with an action date of September 30, 2020, under the Prescription Drug User Fee Act (PDUFA).
For context, it is worth noting that many regulatory bodies internationally draw on the FDA as a benchmark for their decisions, but if there is a negative outcome in the US it would not necessarily be a death knell for the product.
Remestemcel-L is already sold over the counter in Japan, where it is marketed as 'TEMCELL'. In the fourth quarter Mesoblast generated US$2.1 million in royalties from its Japanese partner from JCR Pharmaceuticals Co. Ltd and made manufacturing payments of US$7.4 million for commercial manufacturing investment to support the potential launch of Ryoncil.Never miss a news update, subscribe here. Follow us on Facebook, LinkedIn, Instagram and Twitter.
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