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Post by imz72 on Mar 18, 2017 1:01:16 GMT
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Post by jckrdu on Mar 18, 2017 2:12:17 GMT
Nice!
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Post by selluwud on Mar 18, 2017 12:37:01 GMT
I've always thought there was a lot of potential here. Small start up stage biotech companies are fighting an uphill battle to break through to drug approval and profitability. It's still a long road in front of Athersys but they have managed to get through some rough spots with their Pfizer backed IBD trials and studies and the early stroke trials with the 48 hour treatment parameter. Hopeful for eventual success and approval in the newer stroke trials.
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Post by survtech on Mar 18, 2017 18:09:41 GMT
The CBS report is the result of what Gil said in the recent Earnings Conference Call: "However, despite our success in building revenue through partnering initiatives and other activities over the past couple of years, our promising clinical data announced last year, and the recent significant regulatory achievements that illustrate our clear and efficient path forward, we believe our stock remains meaningfully undervalued. Accordingly, we have taken steps to address that issue. In particular late last year, we engaged both a new media relations and communications firm and a new investor relations firm. Over the past few weeks, we have been working actively with both firms to refine and implement a strategy designed to increase visibility and awareness and we are confident those efforts will be successful. Although it's worth noting that achieving the type of visibility that we believe we deserve will take time and sustained effort." Apparently, the "new media relations and communications firm" is Russo Partners. David Schull, their CEO, posted tweets yesterday saying: "@athersys #MultiStem #stroke treament featured on #cbsnews broadcasts nationwide youtu.be/Ui2WPt9vaDM @cbsnews @russopartners" "This #cbssports broadcaster took an in-depth look at @athersys #MultiStem #stroke treatment during Super Bowl week youtu.be/_ITIvzIoEO0" "UTHealth stroke researchers on the leading edge of stem cell science www.uth.edu/media/story.htm?id=52f594ec-41de-44c2-90b6-d515667063cb#.WMyT0YNgsCw.twitter …" The tweets started not long after the market closed and CBS network news started showing the segments on their 6:00 broadcasts. That would explain the PPS pop from its $1.15 closing price to $1.22 at 6:57 Eastern time. Fingers crossed the PPS rise is sustainable and continues next week. I have to wonder at the timing of the release on a Friday after the market closed. I would think the story would have better "legs" if it was released earlier in the week. Perhaps Russo Partners has plans to continue the push longer term? |
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Post by CM kipper007 on Mar 21, 2017 2:29:48 GMT
There's a guy on Twitter that's saying the lancet article is poorly written and confirms lack of any benefit.
I've seen his tweets before and he comes across a little hot headed before.
Ive not read the full article, but my pony up the cash for this one.
Just curious if anyone had read it and what they thought?
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Post by morangie777 on Mar 21, 2017 3:10:11 GMT
There's a guy on Twitter that's saying the lancet article is poorly written and confirms lack of any benefit. I've seen his tweets before and he comes across a little hot headed before. Ive not read the full article, but my pony up the cash for this one. Just curious if anyone had read it and what they thought? Twitter is not a place for anyone - including the president - to make a well laid out argument for or against anything. Still, you got a link to this guys post? |
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Post by survtech on Mar 21, 2017 4:33:14 GMT
You must be referring to Alexey Bersenev –
@cells_nnm.
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Post by CM kipper007 on Mar 21, 2017 5:02:14 GMT
There's a guy on Twitter that's saying the lancet article is poorly written and confirms lack of any benefit. I've seen his tweets before and he comes across a little hot headed before. Ive not read the full article, but my pony up the cash for this one. Just curious if anyone had read it and what they thought? Twitter is not a place for anyone - including the president - to make a well laid out argument for or against anything. Still, you got a link to this guys post? @princetongb is the account. |
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Post by survtech on Mar 21, 2017 14:03:43 GMT
Oh, him. A smug, arrogant a** if there ever was one. No wonder I didn't see his tweet. He blocked me when we argued about the stroke data a year ago.
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Post by morangie777 on Mar 24, 2017 21:35:57 GMT
So I have read the full Lancet Article, forward, backward, and upside down, thought I'd share my impressions here.
The trial used Global Stroke Recovery as primary endpoint. None of the 2 planned trials is going to use that, so I focused my attention on the data related to the 2 new primary endpoints at 90 days
Excellent Outcome (Japan)
mRS Shift (US/EU)
Excellent Outcome in MultiStem Group All (n=65), 10 (15%)
Excellent Outcome in MultiStem Group < 36h (n=31), 5 (16%)
-> more or less same ratio, between later and earlier groups
Placebo Group (n=61), 4 (7%)
-> p-Value 0.1 (All) or 0.14 (<36h)
My take away here is that yes, the MultiStem Group performs better in this end point, but achieving statistical significance ( p < 0.05) is not a done deal, especially since there was no real difference in the EO ratio of the MS group after excluding the >36h patients.
Japan Trial is going to increase the sample size to 220, assuming some drop outs, let's say we get data from 200 patients in the end. So the sample size is larger, albeit less than 2x as large. IF we get the same distribution of outcomes in the 200 patient sample group, the resulting p-Value is going to be much smaller, and <0.05.
If I am not mistaken, but I am no statistician, if in Study 1 you get a p value of p=0.10, and in study 2 you double the sample size, but the distribution of results is hypothetically identical, your p-value for study 2 would be 0.1 x 0.1 = 0.01 (maybe someone can confirm or correct that….)
mRS Shift
mRS shift looks at improvements in the full range of the mRS scale. Detailed per patient data was not provided in the report, just the resulting p-Values together with mRS data for the 2 best outcomes mRS<=2 and mRS<=1 groups.
MultiStem Group All vs Placebo All: p-Value 0.29 (mRS <=2: 24 (37%) vs 22 (36%))
MultiStem Group < 36h vs Placebo All: p-Value 0.13 (mRS <=2: 14 (45%) vs 22 (36%))
The US/EU trial is said to enroll 300 patients. So the sample size is more than doubled. Theoretically the power should be large enough, to result in p<0.05 given identical distribution, but you see that the differences are not gigantic, so also here it is not a done deal yet.
Other positives
Secondary infections, hospital time, 1 year data all look very strong for MS.
With the new Storage, Thawing, Delivery process not only will they eliminate >36h treatments, but also the <36h group will on average be treated several hours earlier, and from all we know that should further enhance the results for the <36h group compared to the previous trial.
The MS<36h group was only 31 patients big, so the statistical power was small. Having 100 or more patients <36h will further drive statistical significance
Other negatives
Secondary infections, hospital time, 1 year data are not primary endpoints.
Baseline, patient selection, was slightly in favor of MS group (but we have to keep in mind too that patients that received standard of care and showed rapid improvement were excluded).
Patients who had reperfusion therapy (tPA,endovascular thrombectomy, or both)
MS: 38 (59%) Plac: 32 (53%)
A risk is, if that is not better managed next time, that patient selection could be slightly in favor of Placebo group.
Bottom line. Some have called/asked to run the new trials with a smaller number of patients, or have asked for interim data read out, I say we want none of that. To not risk reaching statistical significance in the primary endpoints.
But with the larger sample sizes, together with the improved delivery procedure, I remain positive that this can be achieved.
I hope that a US/EU partner shares this view, and soon. We need some action here, it is getting a bit boring. GLTA.
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Post by survtech on Mar 25, 2017 5:20:37 GMT
One thing I believe you missed in your assessment is the addition of the 18-24 hour treatment group. It's been mentioned at least a couple of times that within the 24-36 hour post hoc analysis patients who received earlier dosing had better responses.
When you add Gil's statements to the effect that they expect to dose even earlier once MultiStem is commercialized and that apparently the immune response starts earlier in humans than in mice, I would expect the P3 trials should show better results.
I posit that we might eventually see dosing as early as immediately or soon after the window for mechanical reperfusion closes (6-8 hours).
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Post by tmfbmf on Mar 25, 2017 14:18:30 GMT
Surv, I spoke to Gil about the earliest treatment time once it is commercialized. He thinks about 8 hours might be the earliest; any sooner and the cells won't impact the spleen at the optimal time. It happens to coincide nicely with current treatment also.
Morangie, thanks for your analysis. I just want to add one thing about "(but we have to keep in mind too that patients that received standard of care and showed rapid improvement were excluded)." Gil has said there were some patients, presumably placebo patients, who showed improvement but were mistakenly allowed into the study. I have been assured these mistakes will not happen in PIII. In the small PII a few patients can and did really skew the numbers.
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Post by morangie777 on Mar 25, 2017 14:21:26 GMT
One thing I believe you missed in your assessment is the addition of the 18-24 hour treatment group. It's been mentioned at least a couple of times that within the 24-36 hour post hoc analysis patients who received earlier dosing had better responses. When you add Gil's statements to the effect that they expect to dose even earlier once MultiStem is commercialized and that apparently the immune response starts earlier in humans than in mice, I would expect the P3 trials should show better results. I posit that we might eventually see dosing as early as immediately or soon after the window for mechanical reperfusion closes (6-8 hours). Agreed. That gives me some confidence too. I don't have the report in front of me right now, but I believe it said the average onset to treatment time was around 37h. Bringing this down will be key. |
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Post by jckrdu on Mar 25, 2017 15:00:13 GMT
Good analysis and discussion. The other thing to remember is that they don't necessarily have to meet the primary endpoints to cross the bar needed for conditional approval.
Signs of efficacy = Conditional Approval (& Revenue)
Meet the Endpoints = Full Approval (& Revenue)
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Post by morangie777 on Mar 26, 2017 0:26:21 GMT
Good analysis and discussion. The other thing to remember is that they don't necessarily have to meet the primary endpoints to cross the bar needed for conditional approval. Signs of efficacy = Conditional Approval (& Revenue) Meet the Endpoints = Full Approval (& Revenue) I don't think it will come to that, and it would not be good news if it did. 1. While this may work in Japan, this will be desaster news for US/EU trial. 2. While it may be approved - conditionally- , I am not too confident that the Japanese insurers will jump on board with paying premiums for something that maybe works, the price paid may be very low, until full approval - which may or may not ever happen - , nor will a part of the patients be too keen on using it. |
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Post by jckrdu on Mar 26, 2017 12:15:38 GMT
Good analysis and discussion. The other thing to remember is that they don't necessarily have to meet the primary endpoints to cross the bar needed for conditional approval. Signs of efficacy = Conditional Approval (& Revenue) Meet the Endpoints = Full Approval (& Revenue) I don't think it will come to that, and it would not be good news if it did. 1. While this may work in Japan, this will be desaster news for US/EU trial. 2. While it may be approved - conditionally- , I am not too confident that the Japanese insurers will jump on board with paying premiums for something that maybe works, the price paid may be very low, until full approval - which may or may not ever happen - , nor will a part of the patients be too keen on using it. On #1, I tend to agree... although the primary endpoint is different for the US/EU trial, so if they don't meet the primary endpoint in Japan, that doesn't mean (with 100% certainty) they'll miss the primary endpoint in the US/EU trial.
On #2, may have to agree to disagree. Some thoughts... My understanding is that Japan is a single payer system, so the federal government will be the only entity determining if it'll be reimbursed. If the Japanese government grants conditional approval, that means it will be reimbursed.
If its reimbursed and someone has a stroke and misses the TPA/reperfusion window, IMO the overwhelming majority will choose to get treatment with MultiStem. (Why wouldn't they if there are no other treatments and the government will pay for it?)
So, the only issue up for debate (IMO) is what the reimbursement rate would be for a conditionally approved product versus a fully approved product. That's a good question. While it may be lower, I don't think it'll be that much lower for the following reason:
The entire reason why the Japanese Government implemented their new accelerated/conditional approval pathway 2-3 years ago was to entice/motivate multi-national companies like Athersys & Mesoblast to bring their trials/products to Japan. Why would Athersys/Mesoblast and other companies change their entire corporate strategy/plans to move aggressively into Japan if the potential revenue from conditional approval is significantly lower (or would have no meaningful impact) than the revenue from full approval? They wouldn't, which is why I believe the revenue/reimbursement rate from conditional approval will be the same (or very close to) the revenue/reimbursement rate for full approval. The only downside for conditional approval is that Helios will have the added burden/cost of running more confirmatory trials to get the full approval designation.
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Post by survtech on Mar 26, 2017 16:24:11 GMT
I don't think it will come to that, and it would not be good news if it did. 1. While this may work in Japan, this will be desaster news for US/EU trial. 2. While it may be approved - conditionally- , I am not too confident that the Japanese insurers will jump on board with paying premiums for something that maybe works, the price paid may be very low, until full approval - which may or may not ever happen - , nor will a part of the patients be too keen on using it. On #1, I tend to agree... although the primary endpoint is different for the US/EU trial, so if they don't meet the primary endpoint in Japan, that doesn't mean (with 100% certainty) they'll miss the primary endpoint in the US/EU trial.
On #2, may have to agree to disagree. Some thoughts... My understanding is that Japan is a single payer system, so the federal government will be the only entity determining if it'll be reimbursed. If the Japanese government grants conditional approval, that means it will be reimbursed.
If its reimbursed and someone has a stroke and misses the TPA/reperfusion window, IMO the overwhelming majority will choose to get treatment with MultiStem. (Why wouldn't they if there are no other treatments and the government will pay for it?)
So, the only issue up for debate (IMO) is what the reimbursement rate would be for a conditionally approved product versus a fully approved product. That's a good question. While it may be lower, I don't think it'll be that much lower for the following reason:
The entire reason why the Japanese Government implemented their new accelerated/conditional approval pathway 2-3 years ago was to entice/motivate multi-national companies like Athersys & Mesoblast to bring their trials/products to Japan. Why would Athersys/Mesoblast and other companies change their entire corporate strategy/plans to move aggressively into Japan if the potential revenue from conditional approval is significantly lower (or would have no meaningful impact) than the revenue from full approval? They wouldn't, which is why I believe the revenue/reimbursement rate from conditional approval will be the same (or very close to) the revenue/reimbursement rate for full approval. The only downside for conditional approval is that Helios will have the added burden/cost of running more confirmatory trials to get the full approval designation.
#2: Japan has compulsory national healthcare insurance. It is similar in some respects to ACA (Obamacare) in that all residents of Japan are required by the law to have health insurance coverage. People without insurance from employers can participate in a national health insurance program, administered by local governments. Japanese pay up to 30% of costs while the government pays 70%+ (depending on family income and age) so in that respect, it is not a true single payer system like Canada's, where the government pays pretty much 100% of the costs. Uninsured patients are responsible for paying 100% of their medical fees, but fees are waived for low-income households receiving a government subsidy. Fees are also waived for homeless people brought to the hospital by ambulance. Of interest, Japan pays about 8.5% of GDP on healthcare - about 1/2 what the U.S. system pays. One example I saw was the cost of an MRI. In the U.S., the average cost of an MRI of the neck was $1,500 in 2009. In Japan, the cost was $98. If not for extensive lobbying by the healthcare industry, we could have a similar system. So even though Japanese citizens have to pay up to 30% of the cost of their healthcare, that's 30% of 1/2, or only up to 15% of what many insured in our system pay. Most premium U.S. insurance typically pays 80% of the cost of treatments up to a "maximum out-of-pocket" amount Japan has similar percentages but of greatly reduced prices so the net cost to the insured is lower. Reimbursement rates are determined by the Minister of the MHLW (Ministry of Health, Labour and Welfare) and published in the National Health Insurance (NHI) Price List. For new pharmaceuticals, especially for innovative new medicines which have no pricing history, MHLW's Economic Affairs Division will hold hearing(s) with participation of the manufacturer, MHLW's Medical Economics Division and other experts. Among the items discussed are: - Presence of similar drugs - Suitability of similar or optimally similar drugs - Necessity of applying premiums - Evaluation of cost price, etc. A pricing draft based on majority opinion of members is distributed to all parties and assuming no one objects, the draft is submitted to Central Social Insurance Medical Council (Chuikyo) a separate body within the MHLW who publishes the drug price(s). If someone (usually the manufacturer) objects to the determined price, the "experts" (excluding the manufacturer) hold a second meeting where a final price decision is made. The results of that decision are published by Chuikyo. |
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Post by survtech on Mar 26, 2017 18:38:24 GMT
Here is an interesting read on navigating the Japanese health care system from the perspective of a Brit www.tofugu.com/japan/medical-system/. G.B. does have a single payer system that is funded by general taxes although Brits can also obtain private health insurance - for a price. 10% of Britons have private health insurance. Private health insurance replicates the coverage provided by the NHS, but gives patients access to higher quality care, and reduced waiting times. The British single-payer system is explained here: healthcare-economist.com/2008/04/23/health-care-around-the-world-great-britain/. Like many single-payer systems, the British system has its flaws. "In 2004, the NHS negotiated lower salaries for doctors in exchange for reduced work hours. Few physicians are available at night or on weekends. Because of low compensation, there is a significant shortage of specialists." "Waiting lists are a huge problem in Great Britain. Some examples: 750,000 are on waiting lists for hospital admission; 40% of cancer patients are never able to see an oncologist; there is explicit rationing for services such as kidney dialysis, open heart surgery and care for the terminally ill. Further, minimum waiting times have been instituted to reduce costs. “A top-flight hospital like Suffolk Est PCT was ordered to impose a minimum waiting time of at least 122 days before patients could be treated or the hospital would lose a portion of its funding.”" |
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Post by morangie777 on Mar 28, 2017 16:09:00 GMT
I don't think it will come to that, and it would not be good news if it did. 1. While this may work in Japan, this will be desaster news for US/EU trial. 2. While it may be approved - conditionally- , I am not too confident that the Japanese insurers will jump on board with paying premiums for something that maybe works, the price paid may be very low, until full approval - which may or may not ever happen - , nor will a part of the patients be too keen on using it. On #1, I tend to agree... although the primary endpoint is different for the US/EU trial, so if they don't meet the primary endpoint in Japan, that doesn't mean (with 100% certainty) they'll miss the primary endpoint in the US/EU trial.
On #2, may have to agree to disagree. Some thoughts... My understanding is that Japan is a single payer system, so the federal government will be the only entity determining if it'll be reimbursed. If the Japanese government grants conditional approval, that means it will be reimbursed.
If its reimbursed and someone has a stroke and misses the TPA/reperfusion window, IMO the overwhelming majority will choose to get treatment with MultiStem. (Why wouldn't they if there are no other treatments and the government will pay for it?)
So, the only issue up for debate (IMO) is what the reimbursement rate would be for a conditionally approved product versus a fully approved product. That's a good question. While it may be lower, I don't think it'll be that much lower for the following reason:
The entire reason why the Japanese Government implemented their new accelerated/conditional approval pathway 2-3 years ago was to entice/motivate multi-national companies like Athersys & Mesoblast to bring their trials/products to Japan. Why would Athersys/Mesoblast and other companies change their entire corporate strategy/plans to move aggressively into Japan if the potential revenue from conditional approval is significantly lower (or would have no meaningful impact) than the revenue from full approval? They wouldn't, which is why I believe the revenue/reimbursement rate from conditional approval will be the same (or very close to) the revenue/reimbursement rate for full approval. The only downside for conditional approval is that Helios will have the added burden/cost of running more confirmatory trials to get the full approval designation.
Good points, we're pretty much on the same page. I just disagree on the bolded above. The new accelerated approval pathway in Japan significantly cuts the time and trials required to full approval. That is why companies move their trials to Japan. And sufficient reason all by itself. The add-on "conditional approval" is not a motivator for any company to move to Japan, it would be like admitting trial failure before you even get started. Of course this is just my own conjecture. |
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Post by morangie777 on Mar 28, 2017 16:12:44 GMT
Thanks surv for a glimpse into the Japanese system.
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