Ohmtaxi, Prochymal and Multistem are both going after bowel autoimmune. The difference is Osiris/Mesoblast are designing trials with four rounds of infusion which has proven successful, and they are in Phase 3 looking to go to market soon.
Meanwhile, Pfizer and Gil have designed and approved, respectively, a FAILED phase 2 UC trial. We keep waiting on a miracle to happen in which Pfizer explains the mystery of their wisdom in designing a failed trial. I am sure they just did not want to design a successful trial because they want to buy ATHX out at a low price! That's it! Or perhaps they "got what they wanted" in terms of defining biochemical success and will find another way to undercut Athersys.
Optimistically speaking, if they indeed liked what they saw, they should be designing a second Phase 2 very soon. Regardless, Osiris/Mesoblast are already beyond this.
With Pfizer, all we have left is hope.
Here you go Ohmtaxi.
Do you understand why the Mesoblast/Osiris data is relevant to the ATHX board now?
Competition is a good thing, and Multistem and Prochymal have a key common effect, increase in IL-4 and IL-10. This is good because Multistem is 1/4 the cost per dose with more cells.
Co-localization of transplanted MAPC and resident CD4+ splenocytes is associated with a global increase in IL-4 and IL-10 production and stabilization of the cerebral microvasculature tight junction proteins. (MAPC were obtained from Athersys, Inc. (Cleveland, OH).
Additionally, Prochymal up-regulates the production of beneficial anti-inflammatory cytokines, specifically interleukin-10 and interleukin-4.
Preliminary findings from the first human study of a monoclonal antibody to mucosal adressin cell adhesion molecule (MAdCAM), PF-00547,659, suggest that it might be useful for ulcerative colitis treatment.The homing of leukocytes to the gut mucosa is a known therapeutic target in IBD as shown by the development of natalizumab; however, this drug is associated with an increased risk of progressive multifocal leukoencephalopathy.
Mesoblast has an advanced program to develop Prochymal® (remestemcel-L, human mesenchymal stem cells for intravenous infusion) for the treatment of patients with refractory moderate to severe Crohn's Disease (CD).
Prochymal® has demonstrated immunomodulatory properties to regulate T-cell mediated inflammatory responses by inhibiting T-cell proliferation (demonstrated in a mixed lymphocyte reaction2) and down-regulating the production of the pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon gamma.
More critically, mesenchymal lineage stem cells have been shown to be capable of effective down-regulation of Th17 cells, reduction in IL-17 levels, and induction of FoxP3 regulatory T cells.
A Phase 3 multi-centered, double-blind, randomized, placebo-controlled trial is evaluating the safety and efficacy of Prochymal® in moderate to severe CD in patients who are resistant to steroid, immunosuppressant and a biologic therapy. The primary endpoint is the proportion of patients experiencing disease remission within 28 days of treatment with Prochymal®, compared to those patients receiving placebo.
Preliminary data from two interim analyses planned under the protocol has provided encouraging results. The Phase 3 trial is ongoing.
An alternative hypothesis is that Pfizer wanted to taint stem cells for UC to promote their own small molecule.
Pfizer Key Programs Registration / Phase 3
Xeljanz® (tofacitinib) – Ulcerative Colitis
Regardless, Pfizer designed the Multistem UC trial to fail because they knew Osiris required 4+ doses of Prochymal to provide therapeutic value.
Any way you cut it, Pfizer used Multistem with wreckless disregard for patients, and I am going on the record with this one. This study was beyond a reasonable long shot. One dose to treat patients is not responsible or fair to the patient. There is no excsure for this, especially without a multi dose followup option. Shame on Pfizer!
Pfizer is going directly after the small molecules secreted by Multistem. They wanted to see if there was a hint of efficacy. If so, they can leave Multistem and synthesize what Multistem produces to sell it as a combo small molecule therapy.
They do not plan to mess around with variable cell cultures that could become infected in bioreactors or deal with batch to batch (donor to donor) variation. I suspect they got what they wanted and will soon cut bait.
By designing trial to fail, they got their efficacy data in terms of a biochemical reponse and can drop Athersys and the patients like a sack of potatoes.
Pfizer screwed Athersys by giving a single dose.
They should have known better based on Osiris results.
Extended Evaluation of PROCHYMAL® Adult Human Stem Cells for Treatment-Resistant Moderate-to-Severe Crohn's Disease
This study has been completed.
Study Start Date: October 2007
Study Completion Date: July 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
May 6, 2010
Osiris Restarts Phase III Prochymal Trial in Crohn Disease Following Interim Analysis
"To understand the significance of this trial, it is important to appreciate just how sick these patients were," said Dr. Onken. "On average, they had suffered with Crohn's disease for 14 years and were unable to find relief with currently available therapy. It was in this difficult-to-treat population that we observed clinical improvement upon administration of the stem cell therapy."
Drug: PROCHYMAL adult human mesenchymal stem cells
intravenous infusion four times over two weeks; possibly repeated once
Osiris would never approve a bowel treatment design using a single dose to cure long-term UC patients.
Take a look at the Osiris (now Mesoblast) treatment design from 2007. Four doses.
Pfizer knew one dose of Multistem would not work! What a scam!
Look below, Osiris used FOUR doses minimum to get results.
*****Drug: PROCHYMAL adult human mesenchymal stem cells
intravenous infusion FOUR times over two weeks; possibly repeated once*****
Pfizer set their trial up to fail.
Ohmtaxi and Biospy, use your ignore button if you do not like what you read. The point here is that any buy or sell is likely too early to be based on any insider knowledge. We simply are not far enough along. Insider knowledge is very much possible though as I have explained.
However, the study is grossly under powered, and I have seen insiders with knowledge of failure buy into disaster. So insider buying means "0". It never has, and it never will mean anything. Even total holding means nothing.
This is a risky one, so bet only what you can afford to lose and hope for the best. Disclosure: I am long and have been for longer than most on this board. I assure you this.
Was Pfizer's "impossible to succeed" Multistem phase 2 for UC trial design (as admitted by Gil) an accident?
Key Programs in Registration / Phase 3
Xeljanz® (tofacitinib) – Ulcerative Colitis, Psoriasis (oral), Psoriatic Arthritis
The UC treatments were also double blinded as well, but I suspect they (safety, Athersys, and CRO) could see that nothing was dramatically different across all of the patients weeks or month(s) before the press release. They know the number of patients receiving Multistem vs. placebo, and it is simple enough to do the calculation to determine how many and to what degree of difference is required to meet the primary outcome measure. If there is no way to achieve p 0.05, regardless of knowing the treatment, then there is no difference, and the trial fails. Likewise, a big difference should reveal itself, although because it is blinded one could argue the placebo outperforms Multistem.
Stroke is difficult because of natural recovery, and Athersys really needs to enroll more patients. If they could enroll even 25 more patients in each arm, this might mean the difference in determining if there really is benefit or simply being unable to prove the difference because the design sucks as it did for UC and they were happy to progress this trial under Pfizer. Of course Pfizer has drugs for UC and benefits from a failed UC trial. Go figure. An investment to fail a trial makes perfect sense.
The enrollment number as it stands now for Multistem stroke is razor thin in being able to prove effectiveness, even if it does exist. More likely they will be unable to prove the benefit because of too few patients, which equates to a failure, and it "black lists" Multistem for stroke altogether. No one will want to pay money in the future to do another trial if the first trial fails.
The well will have been effectively poisoned. If Gil wants this trial to work, I suggest prayer. Otherwise the patients numbers are so low, I question the motivation here.
Management and CRO staff should be able to do the math and predict success or failure with a high degree of confidence at about 75-80% patient completion.
Medpace is the CRO.
Docs and staff at each enrolling hospital would have difficulty determining success or failure because of the lack of sufficient data at any one location and the fact that stroke victms do sometimes recover over time.
CRO staff, safety monitoring, and Athersys should be able to determine a trend early based on past history of stroke placebo outcomes. If it is close, it may be difficult to determine, but if the difference are large, the writing will be on the wall...early!
Again people in the know would be:
1. CRO staff
2. Athersys management
3. Safety folks who review data
All would have access to outcome data that could be compared to an established placebo trend to predict success or failure. I would say this data would be availabe by mid November if not before. By then, they should have a clue if the difference is substantial.
Sentiment: Strong Buy
I hope you are right about Japan and looking on the bright side if we miss the primary yet show significance for the secondary outcome measure(s). Missing the primary though would be brand damaging, no more grant money or easy retail money to move Multistem forward.
A failed phase 2 can poison the well, not just for the casual investor, but for the entire company. At some point, the institutional investors pull the plug. A failed strok trail will be the end of the road for Multistem. There are too many other options out there. Expecting second chances is being too optimistic.
Ohmtaxi, where is the money going to come from to keep the doors open? If the stroke trial fails, all confidence will be lost. I doubt Mesoblast is going to buy us out as they did Osiris. Gil does not expect to be successful at everything he does, but come on, how can Multistem survive another failure suggesting it is no better than chicken soup? We must succeed in the stroke trial.
Ah....yes....I know this.
Jakafi is for an entirely different indication.
The Jakafi example was to illustrate the need for multiple doses to affect the spleen.
Most therapies require multiple doses, but Multistem is different, it is "magical" and only takes one dose.
Anyone saying anything different is spreading "misinformation".
Rrrright.....Survtech10.....one dose it all it takes....got it.
Glad we straightend this out.
Sentiment: Strong Buy
Well, no, we lose our money.
Then someone else does another study.