Hi @dachopper "Expect a lot of off label use in this case" I...

Hi @dachopper "Expect a lot of off label use in this case"
I would be grateful if you (would also like to hear other's views) on off label sales of Rem-L
There was a paper (below) on the Mayo Clinic website from 2018
Hands up, pretty useless on this, but my assumption is that the cost range of £1.1m for Ruxolitnib would include all the other treatments including care costs, but for severe cases it will be more than the $1.1m average for a Complete Response and that makes the case for Rem-L even stronger.

We also know that for severe 3 and 4 grades "Rux" does not work over a reasonable timeframe compared to those who were not treated with it. So they will end up having to fork out more that the $1.1m as you can change in the severe cases the Complete Response to a Non Durable Response.

As the people treating GVHD are experts in their field. I find it difficult to believe that the publicity surrounding its approval in August 2023 will not be known to them at the time (also @Wilba32 has undertaken to ring them all and tell them).
It will also be clear as to its efficacy on the worst grades of GvHD. I believe it was @otherperspective (could have been you) who put forward the reasoned argument that given the cost of care, waiting to see (with the severe cases) who did not respond to steroids, given the percentage that go SR would cost more money that giving Rem-L to all who showed the correct "marker" (ie would respond to the treatment). That is before you factor in suffering of children.
With Adults there may well be the question of dosage (bigger people) but I expect they know the amounts already. Given that the approved drug (which the insurance company would have to pay for anyway) doesn't work, why would you not give Rem-L cost approval for off label use and give that approval quickly for Grade 3 & 4 as you know that the $1.1m (5 years ago) you will have to spend will be wasted and lead to more end of life treatment?

I believe you can make the same case for Perianal fistula - Crohn's as a far better option that the surgical interventions such as anal fistula plug, a draining seton, fistulotomy, stoma formation and proctectomy. Again given the effectiveness of the treatment from its current trials, and the cost of surgery after all the pre-surgery treatment costs, Rem-L will have an off label demand that while I suspect may be smaller in this case to start with, will grow exponentially as its cost benefits become known to insurance companies compared to SOC that they are shelling out for.

So post August 2023, imo whatever figure for sales you put on the under 12 GvHD market for SR, you can include a high percentage of all kids under 12 being given it as best practice for severe case for all, and you can at least double that in off label adult sales before approval makes it official. At that point Jakafi for severe cases of GvHD given its lack of durability will simply not be used or more importantly not paid for by the insurance companies.
Mesoblast will be on the radar of the big institutions post August 2023 and the off label sales will only help those late to the party understand where this company is going. The last quarter of this year is going to be fun if you are in the "will be approved camp" (as I am)
Regards
Yelrom

https://www.astctjournal.org/article/S1083-8791(18)30121-6/fulltext
Steroid Refractory Chronic Graft-Versus-Host Disease: Cost-Effectiveness Analysis
Abstract
Given the increasing incidence of chronic graft-versus-host disease (cGVHD) and its rapidly escalating costs due to many lines of drug treatments, we aimed to perform a meta-analysis to assess the comparative effectiveness of various treatment options. Using these results, we then conducted a cost-effectiveness analysis for the frequently utilized agents in steroid-refractory cGVHD. We searched for studies examining tacrolimus, sirolimus, rituximab, ruxolitinib, hydroxychloroquine, imatinib, bortezomib, ibrutinib, extracorporeal photopheresis, pomalidomide, and methotrexate. Studies with a median follow-up period shorter than 6 months and enrolling fewer than 5 patients were excluded. Meta-analysis for overall and organ system–specific GVHD response (overall response [ORR], complete response [CR], and partial response [PR]) was conducted for each intervention. Cost per CR and cost per CR + PR were calculated as the quotient of the 6-month direct treatment cost by CR and CR + PR. Forty-one studies involving 1047 patients were included. CR rates ranged from 7% to 30% with rituximab and methotrexate, respectively, and ORR ranged from 30% to 85% with tacrolimus and ruxolitinib, respectively. Cost per CR ranged from US$1,187,657 with ruxolitinib to US$680 with methotrexate. Cost per ORR ranged from US$453 for methotrexate to US$242,236 for ibrutinib. The most cost-effective strategy was methotrexate for all of the organ systems. Pomalidomide was found to be the least cost-effective treatment for eye, gastrointestinal, fascia/joint, skin, and oral GVHD, and imatinib was found to be the least cost-effective treatment for liver and extracorporeal photopheresis for lung GVHD. We observed huge cost-effectiveness differences among available agents. Attention to economic issues when treating cGVHD is important to recommend how treatments should be sequenced, knowing that many patients will cycle through available agents.