I thought the RA results were quite good. I always thought they'd need a much higher dose anyway. RA is a very tough customer and I can't see anything is handling it apart from corticosteroids and Methotrexate.
Given the state of emergency in RA and the safety profile of MSCs, I don't see how we can even wait for phase 3. I believe there's an ethical case for using MSCs first line for moderate to severe disease for the following reasons:
Biologics don't seem to be up to the job. You need to stop disease getting into the joints at all costs. Once it's there, it's a hard ask for any therapy.
The most effective biologic seems to be Enbrel but even then it's often paired Methotrexate
The real issue with Methotrexate is the discovery of the microbiome in RA. How can you continue to give a drug known to cause gut permeability?
NSAIDs. See above
We should consider current medication is ultimately making patients worse, particularly pediatrics
What else is out there?
Results from a large multi centre study were published in Arthritis and Rheumatology, May 2014, investigating surgery rates in rheumatoid arthritis from 1986-2011. 1986-1999 n=1,465 and 2002-2012 n=1,236. 25 year follow up. This encompasses pre and post biologics era. Conclusion was hand and foot surgery rates have declined but large joint replacement rates have remained the same.
RA is considered a progressive disease that, without appropriate treatment, causes joint damage. But despite treatment joints are being damaged. I do a lot of reading and this word 'despite' keeps cropping up (also in IBD). I would ask if the disease is getting worse despite or because of treatment?
I don't understand how you can state that a disease by its very nature gets progressively worse without taking into account the first-line medication used to treat the inflammation. I've long had misgivings about suppressing the immune too broadly, particularly in children who are not mini adults but designed to get better.
A lot of the same drugs are used for IBD and RA. Rheumatologists were interested in Celegene's Mongersen for IBD but it's been an expensive flop. Gastroenterologists were interested inTofacitinib but seem to have lost interest presumably due to its gastro side effects. How did something that dangerous get approval anyway? The EMA refused a licence for four years over safety concerns. It's being used in biologic refractory RA. Check out the underwhelming reviews. Vedolizumab has come out for IBD but Crohn's response wasn't great. Experts said results suggested better efficacy with ulcerative colitis. That really didn't seem logical to me. Sure enough, just checked early reviews for UC and they're not that good. Patients say it wears off quickly and mention worrying side effects. How do these things even get on the market?
MSB's phase 3 Crohn's Disease candidate never seems to get a mention. Given the similarites between GvHD and IBD when there's gastrointestinal involvement, Temcell growth is IMO a good sign for positive phase 3 CD. I thought Phase 2 CD results were excellent. When I listened to the recent presentation my understanding was MSB's aGvHD candidate was being given right after steroid failure. Am I right in thinking that means it's being given ahead of Sirolimus? If so, IMO that's a good sign because from the reading I've done I formed the impression Sirolimus was quite effective.
I've been following Seattle children's Hospital for years. They're very progressive and highly regarded. The doctors there seem to have no hubris because they listen to parents and incorporate therapy into practice if they see good evidence. It's interesting that Dr Kean seems to be wanting to move away from suppressing the immune system 'too broadly' in GvHD.
There's a delicate balance between treating the GvHD but preserving the graft v cancer. I've read in journals that the appeal of MSCs is that they don't seem to affect the graft v cancer. I hadn't considered this before. I would extend this thinking to autoimmune diseases. My layperson's view is that the immune system is also the repair system.
One gripe I have is that medicine doesn't seem to talk across disciplines but SCH clearly does because they're planning a trial to examine similarites between GvHD and IBD. They've used a MSB product (I assumed Prochymal based on the article posted here but I'm not sure now as it's still in clinical trial) for a child with grade 4 aGvHD. It would therefore occur to them to use MSB product for bowel rescue in IBD.
Doctors in acute medicine are the best and most influential. SCH is one of the best and most influential hospitals. I think this would be a good way in for MSB. The IBD community is every bit as desperate as the RA one. If phase 3 CD is successful, it's a highly lucrative market. Check out Infliximab and Humira revenue for first year.
If you want to find out the truth about something you have to look deeply into it yourself also for more important things than the stock market. IMO Temcell is the key because it gives an indication of how potent anti-inflammatory agents MSB's stem cells are and whether consistency in manufacuring can be maintained. I'm still looking into this and have emailed to ask if the post marketing survey will be publicly available and when that might be.
If the science is bad things will get ugly. If the science is good things will get ugly. We all have to make up our own mind which it is. This is every bit as ugly as I expected and I wouldn't be surprised if it got uglier because medicine is the biggest business of all and revenue is massive. I think a battle is going on. To me in the subtext I inferred a clear declaration. When I read that, I was expecting a counter attack.
All IMO. DYO research and trust your own perception. Good luck to all holders
MSB Price at posting:
$1.25 Sentiment: Hold Disclosure: Held
(20min delay)