I don't have a science background but I've spent the past week reading up on MSCs in journals and researching on the internet and this is my take:
The hype over stem cells and regeneration has obscured an important property of MCSs, which has come to light only in the last couple of years or so -- their anti-inflammatory and immunomodulatory effect. There is much clinical evidence of this. Imo the sp popped on aGVHD results because of the implications for autoimmune conditions. Nearly half of MSC clinical trials are in autoimmune diseases. As a doctor, I'm surprised you're sceptical that a treatment can 'work' across a variety of conditions. We know corticosteroids 'work' for a variety of autoimmune conditions.
Steroid-regractory aGVHD is a small market but you can see the growth of Temcell for yourself. If the treatment was a dud, I think word would have got around by now.
In aGVHD, if a significant number of seriously unwell patients survive when there's a high death rate, that imo is a good sign of cause and effect. So is local injecting with MSCs into a Crohn's fistula and seeing it heal. Fistulas can be very stubborn and challenging to treat. I believe Infliximab has a 50% success rate, but for refractory cases TPN or surgery can be required, both of which carry risks.
If Tigenix's candidate for fistulising Crohn's (not sure if it's local or IV.) is approved, that will be good news for sufferers and also MSB. Fistula-causing is just one type of CD. There's also inflammatory and stricture-causing. IBD is growing market and a significant number of patients don't respond to Infliximab or Humira. In matters of life or death and zero quality of life, a treatment should be used if it's been shown to be safe and, if I can be bold enough to suggest, so far safer than many existing treatments. As a doctor, I'm sure you can think of drugs used therapeutically before their mechanism was fully understood.
Consensus is that all mesenchymal stem cells are not the same. There are differences in manufacturing process, dosage, method of delivery, site of delivery, culture conditions, passage number, how they're preserved. Some lines may just not be as potent as others. Unsurprisingly results have been varied.
MSCs have been the type of stem cell most studied and reported on. It seems that safety doesn't appear to be an issue, which is reassuring. There is also evidence MSCs have anti-microbial properties, mainly in vitro and animal studies (Tigenix, however, has a candidate for sepsis.) An immune modulator that doesn't impair the body's ability to fight infection. That's something momentous for sufferers of autoimmune disease. Many IBD and RA don't respond to biologics or build antibodies to these drugs. While malignancies have been rarer than feared, infections, some serious, have not been uncommon. MSCs could be the next generation biologics.
What do we currently have to follow on from the biologics? Is it the JAK inhibitors? Tofacitinib was refused a licence from the EMA for four years over safety concerns. It will still probably be used for 4th line RA, but how bad is the situation that something like that can get approval?
As for heart failure, I'm not surprised people are sceptical. Cardiologist Darrel Francis, writing in the BMJ, was highly critical of the way CHF trials have been conducted, and C-Cure, a large study, failed in phase 3. All these trials, however, were autologous. It's taken a long time for the message to get through that a patient's own is not best way to go.
I thought Hare et al.'s success with allogeneic MSCs could be due to their anti-inflammatory action, but there does seem to be repair going on. Their work shows reduction in scar size, improvements in neoangeogenesis and contractility. Seems a lot depends on the dose and how it's delivered, especially with scar size. Results have shown improved heart function and quality of life. Hare says it's important to provide imaging. He also says full regeneration may need a combination of stem cells, such as perhaps MSCs and cardiac stem cells (Tigenix use CSCs for their acute HF candidate.)
Phase 3 is always a worrying time. It's not uncommon for a therapy to fail at this stage. Anyone investing in a biotech should be prepared for that. Independent analysis in MSB's CHF trial showing efficacy in 270 patients, however, is a significant number imo. Also, trialling in children is imo a sign of reasonable confidence. That's why I'm cautiously optimistic.
I don't buy that pharma are blind to the value in MSB technology any more than I bought into the notion that 'big money' couldn't see A2M wasn't 'just another dairy company'. The sell down last year was vicious. Those of us who were long never thought it would go that low. If something's valuable, you pretend it isn't. It's an old game.
As time goes on, the lack of a partner is worrying, but all I can do is keep calm and try to think logically. A partnership not materialising because big pharma don't see value in MSB technology is possible but it's only one possibility.
The heart is a very very tough problem. Groups have been at it for over 15 years and results have been modest and varied. I wouldn't be surprised if pharma were still sceptical for reasons mentioned above.
Perhaps MSB have partnership offers but the terms are still unacceptable to them.
If technology is potentially worth billions and disruptive enough as to make many existing drugs obsolete, pharma might want to control, rather than partner. SI and BOD hold a lot of shares. If no partnership materialises and money is running out, the sp drops and then a predator might make a move.
One scenario I'm hoping for is this: I think wealthy and influential people affected by CHF in the US will be lobbying hard for the right to try allogeneic MSC technology, especially now word has got out that autologous is less effective, maybe even dangerous. If (and I do mean if) MSB can replicate results of the magnitude shown by Hare et al., their CHF candidate could be made available to patients heading for heart transplant. I think insurance would reimburse for that. I was surprised to learn heart transplants are covered.
MSCs have suffered from being over hyped as cure-alls which obscured their value as immune regulators. The area is now getting a lot of attention and now and we have CRISPR technology that could further enhance efficacy.
I hold because I believe the science is good, but I think there's a lot more to medicine than good science and I'm fully aware of the risks involved in investing in a biotech at this stage.
As I've said, I don't have a background in science, so please feel free to correct any errors.
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