I question whether GvHD is such a small market. I posted refs that chronic GvHD is on the rise including in children. From my research I formed the opinion it's not under control from any drug. Biggest risk for chronic GvHD is prior acute.
Prof Kurtzberg said she'd use MSCs first line after steroid failure rather than Jakafi. That didn't come as a surprise to me. Assuming approval, I think there's a good chance our product could be used ahead of steroids. This is why:
Consensus is steroids work in 50% of cases; 1/3 of cases have durable response. When we're told that steroids 'work'. what does that actually mean in terms of what patients can expect?
I'm reading not infrequently that patients suffering chronic GvHD are saying they didn't know what they were getting into and if they had they'd never have had a transplant. There's long been the thinking that some degree of GvHD is beneficial because it means the transplant is working. Arai et al's study, to a large extent, disputes this. There seems quite a high risk of cancer return after 3-5 years and a person can be battling cGvHD and cancer at the same time. Patients have put up with GvHD for years thinking that it confers survival benefit. They're becoming informed that this is the old way of thinking. The article below was recently posted on social media:
https://www.fredhutch.org/en/news/center-news/2018/04/advances-chronic-graft-vs-host-disease.htmlI thought this was comment was noteworthy:
"You cannot just measure survival to determine if a treatment is successful, you must also evaluate its potential undesirable effects on quality of life.”
Chronic GvHD is clearly a problem Better prophylaxis is necessary, short of that a change in what's done in the acute stage. For cGvHD Ibrutinib is being studied in combination with corticosteroids. In clinical practice Jakafi seems to be combined with immune suppressants (I've read parents say Jakafi is being prescribed for cGvHD in their young children) Use of broad immune suppressants risks infection and return of cancer. Prof Kurtzberg said a very important thing imo that MSCs don't suppress the immune system.
Addicted SkinJakafi gained approval, although gut and liver response was inferior to our product, as has been discussed. I also question its efficacy for skin because it's usually combined with ECP, which is done in hospital. The study by Zeiser et al doesn't mention sclerodermatous GvHD, which is hard to treat according to the above article. I referred recently to a small study on Jakafi in this application and results were modest. A quarter of patients had serious adverse effects, one of whom died.
Chronic GvHD most commonly affects the skin and steroids tend to be the mainstay for cGvHD. Some patients have been informed they'll be on steroids for the rest of their lives. They mention knocking into things not that hard but sustaining surprising damage. This must be due to thinning skin. It's a concern because of a condition called.
Topical Steroid Withdrawal or
Red Skin Syndrome.Wiki says TSW/RSS is rare and comes from steroid 'misuse'. I strongly dispute both these claims. In fact, when blame is shifted onto patients, that's a red flag for me. Patients start out using on small areas but the effect wears off and they need to use on larger areas and/or are prescribed steroid creams of increasing strength. Eventually the steroids stop working altogether. (If I recall right, this is similar to what SI described when discussing steroid injections in an interview published online on stem cells for CBP.)
Dr Rappaport is a respected dermatologist who has published peer-review literature on RSS. He's seeing many cases misdiagnosed as severe atopic eczema. His website says a child's skin can become addicted in just two to three weeks. ITSAN.org has information and resources for clinicians. The forum has grown from 7000 to 10 000 members in a year. That's a lot of people suffering from a 'rare' condition!
With TSW/RSS the skin is not a barrier which means prophylactic antibiotics are necessary. It's like a second degree burn. The person can drink a lot but regular tests still show up dehydration. The skin sheds and renews, falls off everywhere like sand. It's disfiguring because of edema all over the body. Some sufferers' skin hangs in folds like elephant skin. When I first saw a photo of this I initially thought it was an elderly person, but that turned out not to be the case. Worst of all is the insane itching, patients report as like ants crawling all over the body. It's not uncommon to feel suicidal from this and It can take years to recover. Often, but not always, after the body wins the battle over steroid addiction there is complete resolution of the original atopic eczema. This is the case with my relative who had a severe case but a particularly fast recovery, taking just over a year.
In the wiki article, you'll see photo of a woman holding up her hand. The demarcation line is clearly visible and is usually bilateral. (Itsan logo used to be a red sleeve) Below I posted a link to a study of Jakafi in GvHD. That first photo could be my relative's leg. I already mentioned the issue I have with this study; however, I'm not implying that photo isn't skin GvHD, just commenting on the similarity to RSS. I think that's a good result to get in a week but the edema looks still there; the angle of the photo makes it less visible. My question is whether you can suffer from skin GvHD and RSS at the same time? That's a dreadful thought.
Photos of skin GvHD before and after Jakafi:
https://www.ncbi.nlm.nih.gov/pubmed/26228813 All this is relevant imo to MSB's GvHD product in three ways:
1. Such a body of visual evidence implicates steroids as a perpetuator, if not a cause, of chronic illness. Doctors already consider steroids an inadequate first-line therapy in aGvHD. If MSCs are available but they have to continue giving steroids first-line there's a risk of alienating them imo. Maybe value-based pricing.could be the answer here too?
2.SI mentioned other potential applications. RSS is a likely one imo for those cases admitted to hospital which don't respond to Cyclosporine.
3. This supports imo what SI said years ago about a healing cascade. I've been criticised for comparing MSB's high tech cells to soft things like dietary therapy, FMT or holding off on steroids. But that's not what I'm what saying. There are two fundamentals here: one is MSB's science and the other is the human body. Success of alternative therapies are indicating the body is capable of more than we thought, particularly when it comes to children. Under medical supervision and in a clumsy, labour intensive way you can start your own healing cascade. It will take a very long time but can deliver superior results.
(20min delay)