When going through the trial design of the upcoming P2 aGvHD clinical trial, I realised that the details have been very poorly communicated so far. Hopefully this lack of communication is intentional with more detail explained once recruitment starts, since the alternative would be that management has completely lost touch with the investor base (both current and potential). Harsh?
Ask yourself:
- who can participate?
- who is the "competition"?
- is it different to already approved or (hopefully) soon to be approved treatments and if so, how?
I have tried to summarise the above in a graph using publicly available information. Whilst there are limitations, such as exact timing (real-world vs. textbook when it comes to diagnosis, dosing etc.), for illustrative purposes it will suffice to show some significant differences to other therapies that most believe CYP-001 is in "competition" with:
The obvious difference here being
children (Incyte's Jakafi approved for children aged 12 years and older and Mesoblast's BLA filed Ryoncil for children under 12 years old)
vs. adults (CYP-001 proposed P2 trial).
In the case of adults, you have
newly diagnosed acute GvHD (aGvHD) patients regardless of risk classification (Osiris 265 completed P3 clinical trial in aGvHD)
vs. newly diagnosed acute High Risk (HR)
aGvHD patients (CYP-001 proposed P2 trial)
vs. Steroid-Refractory (SR / and therefore also HR)
aGvHD patients.
The timing when treatment commences is also significantly earlier, the Osiris 265 completed P3 trial started and the CYP-001 proposed P2 trial as starts (ideally)
shortly after diagnosis, concurrently with steroids for 72 hours (deemed "Standard Of Care" or SOC), with Osiris administering the second of up to 6 doses shortly before Cynata's dose 2 of 2 on day 4,
vs. Incyte's Jakafi and Mesoblast's Ryoncil is not administered until
Steroid Refractory has been diagnosed, which can be as early as
3 days (or 72 hours) after starting steroid treatment.
A few points now before as I am unsure this will come up:
Isn't it all the same: aGvHD and SR-aGvHD?
https://hcp.jakafi.com/graft-versus-host-disease/agvhdCan newly diagnosed HR aGvHD adults also be treated using either Incyte's Jakafi (already approved for SR aGvHD) or Mesoblast's Ryoncil (once approved in children)?
In my opinion (please DYOR) this could be deemed off-label use since it wasn't specifically approved in newly diagnosed (Incyte) adults (MSB). Off-label use is up to the treating physician's discretion and could also depend on the patient's financial situation since the therapy would only be reimbursed by insurers/Medicare/Medicaid one the product is listed in an approved compendium specified by Medicare Law.
Given that MSB bought the Osiris stem cell program and with Osiris having conducted a clinical trial in aGvHD patients similar to the CYP-001 proposed P2 trial, wouldn't a physician rather use her/his discretion to administer a therapy off-label that has completed a P3 trial?
A physician could of course do that, yes.
However, sadly, the cost of the total treatment could be a factor. "
Mesoblast expects a treatment course of TEMCELL in an adult Japanese patient to be reimbursed at ¥13,898,880 (A$156,000 / US$113,000) or up to ¥20,848,320 (A$234,000 / US$170,000)." Participating in Cynata's proposed P2 trial will be free of charge.
Another very important aspect would be available data that may (or may not) have an impact on a physician. In the case of Osiris 265:
https://www.fda.gov/media/141131/downloadThe old Osiris 265 data "did not provide evidence of a treatment effect", yet the price of the treatment still needs to be paid and may not be reimbursed.
Here is a list of most of the resources used for the above summary/post:
https://www.asx.com.au/asxpdf/20180223/pdf/43rv9vtsllq190.pdfhttps://www.sec.gov/Archives/edgar/data/1345099/000156459019025087/meso-ex992_7.htmhttp://test.pharmabiz.com/news/osiris-therapeutics-s-prochymal-phase-iii-gvhd-trial-fails-to-meet-endpoint-52421https://clinicaltrials.gov/ct2/show/NCT00562497https://clinicaltrials.gov/ct2/show/NCT05643638https://hcp.jakafi.com/graft-versus-host-disease/steroid-refractory-gvhd-patient-idhttps://hcp.jakafi.com/graft-versus-host-disease/acute-gvhd-treatment-efficacyI hope that some of the above information (once cross-checked and validated) can form part of the company communication going forward, as it would help to inform the market and all shareholders (current and potential) of what the company is actually trying to achieve with this trial.
Please DYOR and correct any of the above if incorrect!
(20min delay)