Could I advance another thought here, too. I don't believe MSB is looking too far ahead atm - it does want/ need to get over 'the line' with FDA & remestemcel-l is right there.
As we all (no doubt) recall, FDA (CBER) submitted MSB's biologics licence application to the FDA's
Oncologic Drugs Advisory Committee (ODAC) in August 2020. That struck me as odd at the time. Everyone knows the outcomes.
FDA has used ODAC for assessments of monoclonal antibodies e.g. ramucirumab in 2020, and has also used ODAC to back it up on its desire to withdraw accelerated approval previously given to certain biologics in the immuno-oncology space e.g. Keytruda, Tecentriq, Opdivo during 2021. That all makes sense.
IMO there was a logical reason (other than docket management, 'pressure of work', sick leave entitlements etc) that the Remestemcel-l BLA was provided by CBER to ODAC for assessment and recommendation, rather than to CTGTAC (the
Cellular, Tissue, and Gene Therapies Advisory Committee). CTGTAC is a committee used by FDA for review and evaluation of data regarding the safety, effectiveness and appropriate use of human cells, human tissues, gene transfer therapies and xenotransplantation products intended for transplantation, implantation, infusion and transfer in the prevention and treatment of human diseases and in reconstruction, repair or replacement of tissues for various conditions. ODAC, on the other hand, reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer & then makes recommendations to the FDA on those products.
In its introductory briefing materials (see
https://www.fda.gov/media/140988/download) , FDA informed ODAC that ODAC was looking at the BLA because:
"
The tissue-damaging inflammation associated with SR-aGVHD is thought to be initiated by alloreactive immune cells present in the HSCT allograft material that target recipient tissues as foreign, which leads to sustained and systemic immune activation. The proposed mode of action for remestemcel-L is a reduction of this pathogenic immune activation mediated by the immunomodulatory bioactivity of MSCs present in the product" (extract)
My research indicates it's not common, but it is possible for CTGTAC and ODAC to
jointly review a single BLA e.g. with Amgen's BLA for Talimogene Laherparepvec (what a mouthful) for treatment of metastatic melanoma. That was a 2015 investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Maybe, FDA (CBER). But that wasn't done in this case. Not sure why.
It seems to me it was all about ruxolitinib, which is itself a Janus kinase inhibitor (i.e. an immunomodulator). As I understand it, the approval of ruxolitinib first came before ODAC in 2011 for myelofibrosis and then polycthemia vera & then was label-extended by FDA on its own to aGvHD in 2019. Ruxolitinib suppresses the immune system & ODAC had seen it previously. It seems to me that consideration must have overwhelmed any thought of getting the CTGTAC members to give Remestemcel-l their thoughts and recommendations. Otherwise, you'd have to suspect FDA (CBER) of trying to manipulate its own adcoms to get a result it wanted, for some reason.
But that would never happen, eh.
So, circling back to the new job advertisement, I think the position description (assuming not a typo) is possibly just because aGvHD is stuck with a need to deal right now with comparison with monoclonal antibodies, JAK-2 inhibitors and other big pharma products atm. Note also, its a full-time Director position - there are people actually doing the advertised role atm in the US, albeit not at that level. Also, if we agree with Novartis that we'll stay in the same bed, we'll have to deal with Incyte and Novartis' interests in ruxolitinib - as a potential competitor - and it's always best to be prepared.
So, a cautiously optimistic and positive note from me.
(20min delay)