MESO action tonight, page-2763

MSB isdeveloping Ryoncil - an IV stem cell therapy for the treatment ofacute graft versus host disease (aGVHD) in paediatrics. aGCHD is apotentially life threatening (up to 70-90% mortality) complication ofbone marrow transplants (indicated for leukemia/lymphoma etc).Ryoncil has been accepted by the FDA for priority review with a PDUFAaction date of US 30th September (1st Oct in AUS).

Whymight the FDA approve Ryoncil?

Probabilitywise:-Oncology therapy's have an average 88% probability of being approvedonce they have been accepted for review (data averaged from resultsfrom Wong et al (2018), Thomas et al (2016), Hay et al (2014), andDiMasi et al (2010)).-As part of the review, the FDA requested a recommendation from theOncologist Drugs Advisory Committee (clinical oncology academics andstatisticians) who on Aug 13th voted 9:1 that the available datasupports the efficacy of Ryoncil.-Ryoncil has been approved in Japan for the last 5 years with strongyoy growth.Benefit-riskethics analysis:-There are no FDA approved treatments for aGCHD in pediatrics and notherapies are considered standard of care.-Ryoncil is effective vs placebo (28d survival 64% vs 38%, 100dsurvival 79% vs 54%).-Adverse Effects of Ryoncil were not statistically different fromplacebo. In fact unapproved treatments (steroids) carry high risk oftoxicity.-aGCHD has a 70-90% mortality rate, there are no FDA approvedtreatments, Ryoncil appears to be effective, risk of doing harm byapproving Ryoncil is low. It seems like the ethical decision is toapprove Ryoncil.

Whymight not the FDA approve Ryoncil?-

The FDA prefers double-blinded, placebo-controlled RCT's to showeffectiveness. However, due to the high mortality rate of aGCHD,enrolling children into an RCT is clearly not ethical. I'd argue thatthe single arm study comparing to an external control population isas good as you're gonna get. It also does not need to be blinded asthe primary endpoint is mortality. The 9:1 ODAC vote seems to supportthis.-The study was small (N=14, N=13). It might be reasonable for the FDAto ask for another (potentially larger) study to replicate theresults which is a risk.-Quality control concerns. The FDA raised concerns that theway MSB measurethe potency of the Ryoncil (CQA's) may not be enough to ensure theclinical effectiveness of the product. I'm no expert in this part butwhen MSB respondedto these concerns in the webcast, they kind of just reiterated theCQA's from their manufacturing were very high but didn't reallyaddress the concern that the CQA's might not translate to clinicaleffectiveness. It might be reasonable for the FDA to ask for moredata on this.-Even if more data is requested, Ryoncil can still be provisionallyapproved.

Conclusion:
TheFDA will likely approve or provisionally approve (with the request ofmore data) Ryoncil therapy for pediatric aGVHD in the US which willstrongly improve the revenue potential of MSB .