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Curious as to where you got wind of this "speculation" on the script numbers. I looked on some of the other message boards including ST and couldn't see anything being suggested.
Protection against ICH
This article was published today in the Journal of American College of Cariology. It outlines the use of dual anti-platelet therapy during cardiac surgery. However, the gains in ischemic protection afforded by DAPT are somewhat offset by increased risk of major bleeding by up to 30% to 70% and a serious complication which is intracranial hemorrhage (ICH). Fatality rates from ICH related to antiplatelet agents remain very high, at up to 60%. Cytosorb is mentioned in the article a strategy to reverse the antiplatelet effect of using oral P2Y12 inhibitors, and thus protection against ICH. Big unmet need.
https://www.jacc.org/doi/10.1016/j.jacc.2021.07.048
CTSO has been struggling for years to advance HemoDefend for pRBC to an FDA trial. The company has also repeatedly said they would look to out-license HemoDefend for pRBC which has not occurred. From the company's comments it appears they are continuing to run the research and development for both of the grant funded HemoDefend-BGA™ (Universal Plasma) and HemoDefend-RBC™ (pRBC) programs but are unlikely to make real progress advancing the RBC product to a trial in the near future. This is because it is a lower priority than the current STAR-T trial. So I would not expect to see any licensing deal or revenue coming from this program even in 2022.
I suspect it is because Ticagrelor (Brilinta) is an antiplatelet agent. Apixaban (Eliquis) and Rivaroxaban (Xarelto) are anticoagulants.
Don't forget that the company has had positive studies also where they demonstrated successful and safe removal of Dabigatran (Pradaxa) and Edoxaban (Savaysa) so I suspect those two agents will be next.
Your veiled attempt to look credible by implying you have reached out to me or that I have an interest in Spectral is pathetic and a lie. I think most of the users on this board by now see through your veiled attempts to pump up that company, but keep trying ... its probably not hard to make an impact on a stock that has an average volume of 15k shares and a 52 week range of .26-.59. :)
My opinion on the Terumo partnership
When I saw this I thought the same thing. I am not sure why I didn't pickup on this earlier (probaby because it has been very quiet since 2016 on the Terumo front in Europe). I think there is more to this partnership than meets the eye.
Just a refresher, back in 2016 CTSO inked a distribution partnership with Terumo for six European countries: France and the Nordic countries of Denmark, Finland, Iceland, Norway, and Sweden, for cardiac surgery applications. There was some overlap with Fresenius who had distribution rights for acute care in most of these same territories before they CTSO negotiated getting those back in exchange for Mexico and South Korea. I think most would admit that it's been pretty quiet on the Terumo European front in terms of news but keep in mind they only had rights to distribute for cardiac surgery and in those territories there are 'only' about 70,000 heart surgeries performed each year vs worldwide there are over close to 2 million.
Baxter and Terumo are chief competitors in the medical device space. Terumo having about $5B in revenue compared to Baxter with $11M in annual revenue. In terms of revenue and size of the company (employees) Baxter is twice as big. Baxter obtained FDA EUA for Oxiris which is their own filter. Baxter also has an exclusive distribution agreement with Spectral for the U.S. and Canda for Toraymyxin which complements their own filter by removing endoxins.
In my opinion, both CTSO and Terumo came together on this to establish this partnership on COVID to fend off further expansion of Baxter's products into more U.S. hospitals, and a prelude to a much bigger partnership with a trial and potential exclusive rights for the removal of ticagrelor and other NOAC's. Remember that some of the risk has been removed for a strategic partner for the removal of NOAC's, whether that be Terumo or someone else, since the FDA has already granted the device breakthrough status. I am also sure Terumo Cardiovascular (this division) has been closely following what's been going on with the removal of ticagrelor and the recent breakthrough designation. As stated in the press release, Cytosorb fits nicely with Terumos other products specifically their CAPIOX ECMO machine and their Advanced Perfusion System heart lung machine. Terumo would also give CTSO access to Japan which is a significant market.
This is the same EUA which was approved back in April.
I saw that it hit the FDA News yesterday but don't know the reason why. Nothing new here.
https://cytosorbents.com/us-fda-authorize-cytosorb-for-use-covid-19/
Advantage of extracorporeal adsorption over other therapeutic approaches
Published today in Critical Care, doctors from University of Freiburg make the argument for extracorporeal cytokine adsorption over the other therapeutic approaches. Freiburg is where the post-cardiac arrest syndrome (CYTER) and COVID-19 (CYCOV-II) trials are being run.
"A major advantage of extracorporeal cytokine adsorption over the other therapeutic approaches discussed in this debate is that it does not selectively block a specific receptor or signal transduction cascade, but it rather reduces particularly elevated concentrations of various inflammatory mediators such as interleukins, TNF-a, and also interferons; these factors have both pro- and anti-inflammatory functions. Only mildly elevated, physiological, or even decreased concentrations are not relevantly altered; thus, over-suppression of the immune response may be prevented ...."
Extracorporeal cytokine adsorption as an alternative to pharmacological inhibition of IL-6 in COVID-19
https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03238-1
Non-cardiac surgery opportunity
Below was a comment made on YMB regarding the latest case of the week:
"Latest Case of the Week (34/2020) is an excellent and obvious expansion of CytoSorb usage to remove ticagrelor / rivoraxaban during urgent off-pump cardiac surgery -- that is, without any CPB machine. It's almost certainly just a matter of time before CTSO can expand CytoSorb's official label for ticagrelor / rivaroxaban removal in the EU to include all these urgent non-CPB cardiac surgeries as well, which validates the bigger addressable market for anti-thrombotic removal that CTSO has been touting as of late. Hopefully, the FDA will eventually expand Breakthrough Designation to include non-CPB cardiac surgeries too."
https://literature.cytosorb-therapy.com/infoitem/elimination-von-ticagrelor-und-rivaroxaban-mit-dem-cytosorb-adsorber-vor-dringlichen-off-pump-koronar-bypass-operationen?lang=en
These observations underly the primary talking point of Dr. Michael Gibson during the recent KOL call which is the future use of Cytosorb to include non-cardiac surgery applications. This greatly broadens Cytosorb usage throughout the hospital and correspondingly makes the market for this indication exponentially greater. Over a 5 year period about 4% of the population will have open heart surgery, however in that same time period about 32% of patients hospitalized that have stents will have some form of non-cardiac surgery (there are about 1M stent surgeries per year). He see's a smaller version of the device potentially being deployable to emergency rooms and patient's rooms in preparation for these procedures.
Areas he highlighted included:
- Cardiac electrophysiology procedures
- Neurosurgical procedures?- to reduce risk of life-threatening bleeding and to avoid surgery (subdural hematomas)
- Acute stroke (NOAC = contraindication for t-PA)
- Urgent orthopedic procedures and
- Urgent GI or oncological procedures
- Trauma
We have learned with the FDA not to get your hopes to high (remember EAP?) so count me as one that also believes a trial will be necessary.
That being said, the company has an advantage of following in the path of Portola with the Andexxa approval. You can see from the comments during the last cc, that what the FDA is looking for has now been established - no second guessing. It sounds like the data from the trial from Hamburg already supports that surrogate marker of platelet aggregation, so I believe this will also be shared with the FDA.
"They've (Portola) established an FDA precedent, that surrogate markers such as platelet aggregation of Factor Xa activity can be used as the primary endpoint for FDA approval and in the sub-study, in the paper coming out of St. Georg Asklepios Hospital in Hamburg, Germany, four out of five or 80% of patients treated with CytoSorb had a rise in the MEA or Multiple Electrode Aggregometry Assay that correlates with the restoration of platelets function giving us additional visibility that if we were to pursue a trial, that we could see benefits here as well. "
A positive note on a down day....
Remember the company has Breakthrough Designation for the removal of ticagrelor so this gives them the opportunity to interact with the FDA's experts in a more expedited and efficient manner, as well as receive feedback from the FDA . Under this designation we can also expect prioritized review of the submission at that point in time.
An interesting article on the Real Value of a Breakthrough Designation:
https://seekingalpha.com/article/4314267-real-value-of-breakthrough-therapy-designation
- Average approval time reduced by 2.5-3.5 years.
- Breakthrough therapy designation usually increases valuation significantly.
- Takeover offers typically increase with breakthrough therapy designations.
- Takeover offers for a company with 2 breakthrough therapy designations increase significantly and quickly.
If the REMOVE data comes back compelling, this could be the 2nd Breakthrough Designation for the company should they decide to pursue it.
Why Novavax, Vaxart, Sorrento Therapeutics, and Other Coronavirus Stocks Plummeted Today
https://www.fool.com/investing/2020/08/12/why-novavax-vaxart-sorrento-therapeutics-and-other/
The unfortunate aspect of having a COVID-related treatment is you rise and fall with the tide.
Thanks raptor, it sounds like you got the options pretty well covered. Still learning about these different approval paths and all the variations of expedited statuses - it can be very confusing.
Hemopure, they stated that the ticagrelor trial would be the fastest, least expensive, highest visibility of any of their applications for potential U.S. approval. Seeing that a Hemodefend pRBC trial was going to be 20 patients and 2 sites and take around 6 months to a year, I find it pretty hard to believe it could be smaller and shorter than that - but then again compared to "not requiring a trial", perhaps this could be true. I will dig around in my notes to see if there was any mention of this from previous calls and report back if I find any references.
Video of Cytosorb use in Iran on COVID patient
This video on You Tube was uploaded today of a COVID 19 Patient in septic shock who requires RRT being hooked up to Cytosorb. Remarkably this was from Anesthesiology and Critical Care Research Center, Shiraz, Fars, Iran.
I say this because you don't hear a lot coming out of Iran (for obvious reasons).
Armaghan Salamat Kish Group (Arsak) is the CTSO partner there.
Thanks for these observations and your insights. This confirms what I am seeing with the current FDA registration that is on file, that it is classified as a Class 2 device under PART 876 -- GASTROENTEROLOGY-UROLOGY DEVICES (same Title 21 that you quote below).
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRL/rl.cfm?lid=427282&lpcd=FLD
The company has several data points/sources that they can bring into the discussions with the FDA including the St. Georg Asklepios Hospital study, the label expansions from the EU, REFRESH II data, TISORB (what little they have collected so far), CYTATION, and the new STAR registry. My guess is one of the reasons for the lack of updates on the FDA approval path is that they are getting all of these sources in a presentable case. From the remarks on the CC, they used the words "very soon" so I suspect we are getting closer to hearing what this approval path will look like. I am just thrilled that Dr. Deliargyris with his background and credentials is leading these discussions with the FDA.
Any thoughts to this comment regarding the FDA approval path?
I missed listening to the conference call again so was reading through the transcripts. The version on SeekingAlpha I found is not as accurate with typos and punctuation so the excerpt below is from Motley Fool.
I don't know if this was just a slip of the tongue but Dr. Chan said it twice in the same discussion regarding the approval path. How can a trial not be needed for ticagrelor removal - is this an option considering the other sources of data they mention (REFRESH 2, TISORB, etc.)? Maybe I just read this wrong.
"We're now in the process of defining the regulatory paths for the therapy with the FDA, whether or not it's a 510(k) versus the de novo 510(k) or PMA. If a clinical trial is needed, competitors such as Portola, that was recently acquired by Alexion for $1.4 billion and PhaseBio that is a public company that is still in the clinical trial phase, they've established an FDA precedent, that surrogate markers such as platelet aggregation of Factor Xa activity can be used as the primary endpoint for FDA approval. And in the sub-study, in the paper coming out of St. Georg Asklepios Hospital in Hamburg, Germany, four out of five or 80% of patients treated with CytoSorb had a rise in the MEA or Multiple Electrode Aggregometry Assay that correlates with the restoration of platelets function giving us additional visibility that if we were to pursue a trial, that we could see benefits here as well." (emphasis added)
Thoughts?
Great post ranchhand and I am in total agreement. If the company can finally get their ducks in a row and get the IDE filed and approved for a Hemodefend trial, the trial itself should go pretty quickly as it has very clear protocols and was to only have required 2 sites and 20 patients.
Very good point orangecat. The usage footprint of the cartridge in hospitals is going to expand, which translates into greater adoption, SOC in some areas and increased sales.
I would also venture to say that the current sales split of 70% critical care and 30% cardiac surgery, could even swing the other way where cardiac surgery comprises a greater percentage of the sales than critical care - the market opportunity is that big.
Dr. Deliargyris said it best:
"With the upcoming results from the REMOVE trial evaluating the intraoperative use of CytoSorb in high risk heart valve replacement surgery for infective endocarditis, the recent E.U. approvals for ticagrelor and rivaroxaban removal during cardiac surgery, and the U.S. FDA Breakthrough Designation for ticagrelor removal during cardiopulmonary bypass, the use of CytoSorb in cardiac surgery represents an incredibly exciting area of potential growth that we plan to pursue aggressively."
The one positive thing coming out of all this is that the company should never have the need for another offering or use the ATM again, so the share price should be free from that overhang.
Cytokine storm syndrome - narrative review
Published a few days ago in the Journal of Internal Medicine (a peer-reviewed scientific journal), this article is from physicians at Zhongda Hospital in Nanjing and Tongji Hospital in Wuhan, China. Tongji as you recall was one of the first hospitals to receive filters through the CMS arrangement.
Cytokine storm syndrome in coronavirus disease 2019: A narrative review
https://onlinelibrary.wiley.com/doi/full/10.1111/joim.13144
"There is growing evidence that cytokine storms caused by the excessive production of inflammatory factors may participate in the pathogenesis of patients with COVID-19, which may be one of the key factors leading to the rapid worsening of the disease. Therefore, early identification and treatment of CSS may be crucial for improving the outcome of critically ill patients with COVID-19. Here, we summarize the pathogenesis, clinical manifestations of CSS, and highlight the current perspective about the recognition and potential therapeutics for CSS in COVID-19."
"CytoSorb®, a recently developed, commercially available haemoadsorption device that utilizes extracorporeal blood purification, is designed to reduce systemic cytokine burden. Numerous case reports and case series have suggested improved clinical outcomes with CytoSorb in patients with septic shock. Recently, CytoSorb® was also reported to be effective in a patient developed CSS after CAR T-cell application. Given that there is excessive production of various cytokines in patients with COVID-19, CytoSorb® may become a potential therapeutic candidate in COVID-19 patients complicated with CSS. Based on the previous experience in the treatment of patients with SARS and MERS and collected clinical experience in treatment of critical ill patients in China, the newly updated version of guidelines for the prevention, diagnosis, and treatment of pneumonia caused by COVID-19 in China also recommended that COVID-19 patients with high inflammatory response could consider to use extracorporeal blood purification technology for removal of cytokines and mitigate CSS."
The $5k savings was from a study done in the UK last year on ticagrelor removal:
CytoSorb® Removal of Ticagrelor Intraoperatively Results in Projected Cost Savings of Approximately $5,000 in Each Patient Undergoing Emergency Cardiac Surgery
https://finance.yahoo.com/news/cytosorb-removal-ticagrelor-intraoperatively-results-110800673.html
"CytoSorb® efficiently and rapidly removes ticagrelor from whole blood, and its usage during emergency cardiac surgery with cardiopulmonary bypass was shown to reduce perioperative bleeding complications in a published observational study by physicians at the Asklepios Klinik St. Georg in Hamburg, Germany. Based on this cornerstone publication, a decision analytic cost-consequences model was applied to estimate health care resource utilization in patients on ticagrelor undergoing emergent cardiac surgery in the United Kingdom. The use of CytoSorb in this patient population significantly reduced morbidities from bleeding, including, on average, fewer blood product transfusions (-0.47 units of red blood cells and -1.16 units of platelets), fewer re-operations (36% in the control versus 0% with CytoSorb, respectively), shorter operation time (-65 minutes), shorter ICU stay (-1 day), and hospital length of stay (-3 days). As a result, CytoSorb reduced overall health care resource utilization in this model by an average of £3,982 per patient (approximately $5,000 USD per patient), including the cost of the CytoSorb adsorber, and resulted in a better health-related quality of life."
From what I remember from the conference call last week with the KOL's on the removal of ticagrelor, they are basing the pricing on what the cost savings were from the UK study on cost-effectiveness last year, that demonstrated a savings of approximately $5,000 per case due to the clinical benefits. If the recording is still available, Dr. Chan does address the $5,000 pricing briefly.
I admit I am also a bit confused because Dr. Schmoeckel was asked during that call how many cartridges are used typically and he said only one.
They must feel that they have the basis for this pricing as it has been mentioned on multiple conference calls and appears in several presentations.
Some highlights from the preliminary Q2 results
• Generated approximately $667,000 in U.S. hospital sales during the second quarter (this was not a full quarter as the EUA was issued in mid-April). The company did not provide a preliminary all up Covid-19 sales number for Q2, but I would suspect that if Q1 sales were $1.5-1.7M, it is probably well over $2M with the U.S. comprising $667k.
• The decline in gross margin to 70% was due to increased costs of an expedited ramp in production
• Cumulative CytoSorb treatments delivered grew to more than 98,000, up from 67,000 a year ago
• Cumulative Covid-19 treatments is in excess of 1200 patients
• Currently anticipate the EUA for Covid-19 will be in place through to Spring 2021.
• REFRESH 2-AKI trial in the U.S., data analysis requested by the Data Safety Monitoring Board (DSMB) is complete, with a committee meeting scheduled this week. Pending a positive DSMB review and readiness of clinical trial sites, the REFRESH 2-AKI trial may be in a position to restart this quarter at a number of centers.
• Full data analysis of the investigator-initiated, 250-patient, 15-center, randomized, controlled REMOVE endocarditis trial is expected in the second half of 2020, with top-line data potentially in Q3
• Regarding the Breakthrough Designation to CytoSorb for the removal of ticagrelor, the company still sees the current addressable market in the United States for ticagrelor removal in cardiac surgery is approximately $250 million, assuming FDA approval for CytoSorb in this application and a price per CytoSorb device of $5,000. In the event that CytoSorb also obtains FDA approval to remove novel oral anticoagulants (“NOACs”) such as rivaroxaban and apixaban, we believe the total addressable market in the United States for ticagrelor and NOAC removal during cardiac surgery could potentially increase to approximately $500 million. In the event that CytoSorb obtains FDA approval to be used prophylactically to remove ticagrelor and NOACs in all patients undergoing surgery, we believe it would potentially expand the total addressable market in the United States to approximately $1.5 billion.
http://cardiacvascularnews.com/cytosorbents-provides-preliminary-q2-2020-financial-results-and-corporate-update/
Swapnil Hiremath, MD responsible for NYT change
This University of Ottawa nephrologist, Swapnil Hiremath, MD, was responsible for the change in downgrading Cytosorb as a Covid-19 therapy.
Ok so @carlzimmer reached out and after a few emails and a phone convo I see that RRT has been removed & Cytosorb downgraded
— Swapnil Hiremath @hswapnil@bsky.social (@hswapnil) July 17, 2020
Not perfect yet but a step in the right direction
See @venkmurthy thread for more https://t.co/tWeXyckBQp
For kidneys, here’s its recommendation for Cytosorb
— Swapnil Hiremath @hswapnil@bsky.social (@hswapnil) July 16, 2020
‘Promising evidence’
How about strong evidence it doesn’t work instead? https://t.co/bpSM0avDir (different method, same principle)
3/ pic.twitter.com/foiOxiktrB
Open Heart journal - Norway experience with DOACS
Published this month in the Open Heart journal:
Operative survival in patients with acute aortic disease in the era of newer oral anticoagulants
https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwijveer59HqAhWHT98KHdzUCG0QFjAIegQICRAB&url=https%3A%2F%2Fopenheart.bmj.com%2Fcontent%2Fopenhrt%2F7%2F2%2Fe001278.full.pdf&usg=AOvVaw0bTds2Gevc1nWiW-nFtPYv
Open Heart journal contains peer reviewed medical research in all disciplines and therapeutic areas of cardiovascular medicine and is the official journal of the British Cardiovascular Society.
This paper outlined a study by cardiothoracic surgeons at Oslo University Hospital in Norway. The study analyzed the risk associated with direct oral anticoagulants (DOACs) in patients undergoing non-elective operations on the proximal aorta due to aortic disease, with an emphasis on operative mortality.
One of the things that stood out to me was the extraordinarily high mortality rate - of 135 non-elective operations between 2016 and to 2018, 19 patients died during the first 90 days. DOAC use was the top-ranked risk factor. In the DOAC group they studied, 30-day mortality rate was 67% versus 9% in patients not using DOAC. All deaths among the DOAC-treated patients were bleeding related, while this was not the case in any of the other groups. Most of the patients using DOAC were also older.
In Norway, DOACs have gained popularity and, of anticoagulant users in 2018, 27% used warfarin and 73% used DOAC. The DOACs are now the most used anticoagulants in Norway. So they are projecting the number of DOAC users requiring acute cardiac surgery to also likely to increase.
Another noteworthy point they made was that only 8% use dabigatran (Pradax), and the surgeons do not yet have experience yet with the dabigatran reversal agent Praxbind. Apixaban (Eliquis) is the most used anticoagulant in Norway and they confirmed that there are concerns over using Andexxa (the only approved reversal agent).
The highlight of the article however was toward the end where they reference the study in Germany and indicate they are watching what is going on with Cytosorb: "In patients using rivaroxaban or ticagrelor, the same group has also described promising effects of CytoSorb®, a whole blood adsorber for extracorporeal purification of blood that may be used with a heart-lung machine during cardiac surgery".
Remember it was only this year that the company received EU approval for the removal of ticagrelor and Rivaroxaban (Xarelto), but as this article demostrates, word is getting out now across the countries in Europe. Because Norway is now a direct sales country (taken back from Fresenius), hopefully this will aid in more rapid adoption.
Some preliminary Covid-19 data for Cytosorb with ECMO - from Freiburg, Germany.
Published July 14, 2020. This bodes well for the results from the CYCOV-II study which is going on there.
Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation
Marina Rieder, Tobias Wengenmayer, Dawid Staudacher, Daniel Duerschmied & Alexander Supady
Critical Care volume 24, Article number: 435 (2020)
https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03130-y?utm_source=other&utm_medium=other&utm_content=null&utm_campaign=BSCN_2_DD01_CN_bmcso_article_paid_XMOL
The treatment of patients with severe COVID-19 requiring support with veno-venous extracorporeal membrane oxygenation (vv-ECMO) is particularly challenging from a medical point of view and consumes a tremendous amount of human, physical, and financial resources. Recommendations for initiation of vv-ECMO in COVID-19 are being developed, though under continuous review. However, despite all therapeutic efforts, these critically ill patients have a high mortality rate according to studies published so far.
At our hospital, a major referral center for extracorporeal support, we have treated several COVID-19 patients with vv-ECMO. Knowing interleukin-6 (IL-6) as a predictor of negative outcome, some patients received cytokine adsorption using the CytoSorb® adsorber (CytoSorbents Europe, Berlin, Germany) shortly after initiation of ECMO for up to 72 h. Based on experience in septic patients, the adsorber was exchanged every 24 h. Integration of the adsorber in the ECMO circuit was feasible and safe. Preliminary data from eight cases (4 patients receiving ECMO with cytokine adsorption, the remaining 4 received ECMO without cytokine adsorption) shows that cytokine adsorption may result in a more pronounced decrease of IL-6 after initiation of ECMO.
Whether this observation can be confirmed in larger cohorts and the degree to which this effect is caused by the adsorber instead of just being a sign of general clinical improvement warrants further investigation. Finally, whether this translates into improved clinical outcome remains to be shown, either.
Therefore, we set up a clinical trial to further examine this preliminary observation. The CYCOV-II study (cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation) is a randomized, controlled, open-label intervention, multicenter trial comparing cytokine adsorption in ECMO treatment for COVID-19 with a control group receiving standard ECMO treatment without cytokine adsorption (Fig. 2; NCT04385771).
Positive affect and markers of inflammation: Discrete positive emotions predict lower levels of inflammatory cytokines.
Negative emotions are reliably associated with not only poorer health but recently research has acknowledged there is a link between negative emotions and proinflammatory cytokines, specifically levels of interleukin-6 (IL-6).
https://psycnet.apa.org/buy/2015-01796-001
Fantom, I would highly recommend you watch it when you have time. I was able to move some things around in my work schedule and attend the entire call and I am glad I did.
I checked this morning and the recording and transcript are available. The link I have however is unique to my login, so you can try going to the original invite link:
https://lifescipartners.zoom.us/webinar/register/WN_QS3pzVugTJy6nw_yUow8SA
- or try this site and click 'Join' and see if it will allow you to register and access the recording:
https://lifescipartners.zoom.us/
They have already proven that a smaller / mini version of the Cytosorb cartridge is effective in removing NOACS.
Dr. Gibson referenced this study in his presentation, which used a 60mL (vs 300mL) cartridge with a reduced flow rate of 40mL/min to remove high plasma concentrations of rivaroxaban (Xarelto) from human whole blood for 120 minutes.
Remarkably within the first hour, 91.6% of the rivaroxaban was removed (for some reason the filter is even more efficient at removing rivaroxaban).
https://www.semanticscholar.org/paper/Extracorporeal-Hemoperfusion-as-a-Potential-Option-Koertge-Wasserkort/6edef590deec458a684f3d94fb9a5e649d8ca5d0#paper-header
I took some notes during the call and screenshots from the presentation which I will post later time permitting here and on ST, because they are worth pointing out.
Probably the most significant thing I took away was the focus on the prevention of bleeding that Dr. Gibson highlighted in much of his presentation. When he says that "Cytosorb is the ONLY strategy that can prevent bleeding in these patients" and he see's a smaller version of the device being used throughout the hospital - not just in the OR, this lends credibility to the potential. He sees the device being used on any patient that is on one of these NOAC's that would be having cardiac electrophysiology procedures, neurosurgical procedures, acute stroke, urgent orthopedic procedures (e.g. broken hip), urgent GI or oncological procedures or trauma.
The reason for a smaller device is that even one as small as 40mL with a lower flow rate can remove up to 96% or more of ticagrelor or rivaroxaban within the first few hours. The doctor from Germany confirmed that only one regular device is needed during cardiac surgery. Having a smaller device means the hospital can use it in any setting and not have to have a bypass pump relocated.
By the way, if you don't know this already the company already makes a small 50mL device - it is called VetResQ :)
https://cytosorbents.com/products/VetResQ/
Agree! This indication is going to be a gold mine.
There was a lot of new information not talked about on previous conference calls - the main one coming from Dr. Gibson about the potential introduction of a smaller size filter (e.g. 40mL device with lower flow rate) which can be used through out a hospital for ANY type of surgery where a patient is on one of these NOAC's. This takes the potential market size from $225M in cardiac surgery to $1.5 billion in the U.S. alone.
KOL call this morning - antithrombotic removal
I forwarded the conference call details along with the information below, to a group of cardiologists from Dallas who may be dialing this morning.
https://cytosorb-therapy.com/en/the-therapy/ticagrelor-and-rivaroxaban/
I am going to try and listen in, but due to work obligations will not be able to stay on for the entire call.
Medtronic, one of the largest device makers in the world and has one of the higher gross margins in the industry is only 67% this year. 10 years ago it was 10 pct points higher but has been steadily declining.
CTSO's gross margin has been steadily increasing. A lot of this has to do with operational efficiencies (which by the way can be partially attributed to the management team).
Cytokine Storm in COVID-19 (Frontiers in Immunology)
Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies
College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01708/full
This article from researchers in China was published a couple of days ago. What I found very interesting is that the only extracorporeal therapy they mentioned in the paper was Cytosorb - no mention at all of Jafron HA330/HA380, which is surprising as it is a China-based company, or Baxter Oxiris.
Potential Treatments for Cytokine Storm in COVID-19 and Their Safety - Cytokine-Adsorption Device
"Cytokine adsorption involves using a method, such as extracorporeal membrane oxygenation (ECMO), to filter harmful substances directly. An extracorporeal cytokine hemoadsorption device called Cytosorb® (Cytosorbents, Monmouth, NJ, USA) has been reported to capture and reduce inflammatory mediators. Bruenger and colleagues reported that the plasma level of IL-6 and procalcitonin decreased in one patient with severe ARDS after Treatment with ECMO using a hemoadsorption device (78). A 45-year-old patient with severe ARDS showed that venous arterial-ECMO combined with hemoadsorption therapy decreased plasma concentrations of IL-6 and IL-8. Moreover, hemodynamic stabilization, respiratory improvement, and a decline in capillary leakage can be achieved in combination therapy (79). Two trials employing hemoadsorption therapy for infection-related cytokine storm are ongoing (NCT04195126, NCT03685383).
A similar therapy involves dialysis. The mainly water-soluble mediators are removed from plasma, and the hemofilters can have additional adsorptive properties (80). Continuous venovenous hemofiltration and adsorption for severe septic shock are being tested in one clinical trial (NCT03974386).
Neutralizing excessive cytokines with hemoadsorption devices might be relatively effective. The disadvantage is like corticosteroids: a wide range of cytokines would be adsorbed. Thus, it would lead to the a lack of cytokines, which are at reasonable or even insufficient levels. We suggest treating the cytokine storm in COVID-19 should base on the laboratory results of cytokines and chemokines. Meanwhile, adjusting the parameters of the devices (e.g., treatment duration) for preventing overtreatment."
Nice to see Cytosorb finally being used in my own state
Houston Methodist
https://twitter.com/DeepaGotur/status/1278778587768918018/photo/1
Product registration in Brazil
I believe the company may have just achieved official product registration in Brazil. This was posted this morning and this is what it appears to me.
https://www.smerp.com.br/anvisa/?ac=prodDetail&anvisaId=80185570007
Medical devices in Brazil are regulated by ANVISA (Agência Nacional de Vigilância Sanitária. Like other countries they have a classification system based on a risk based model and are classified I-IV. Cytosorb has been classified as it is in the states as a class II device. It generally takes for Class I and II devices 4-6 months for the approval/cadastro process.
Contatti Medical is the distributor for Brazil who was brought on board in late 2019. The Brazilian market is robust, serving 210 million people, where among the leading causes of death are heart disease, trauma by traffic-accidents, sepsis, as well as chronic liver and kidney disease. ICU figures in public hospitals show that the mortality rate due to sepsis is huge – around 45%.
Cytosorb getting used in India
Back in April, the Karnataka government in India formed a Critical Care Support Team for advising physicians in COVID-19 cases all of the government hospitals in the region. They were the first region in India to link COVID-19 hospitals across state on a single platform for critical care support, and since then they have also added 483 private hospitals to the treatment network.
This article was published today which lists Cytosorb as one of five key therapies they are using to treat critically ill patients:
Karnataka beefs up treatment protocol
https://www.newindianexpress.com/states/karnataka/2020/jul/05/karnataka-beefs-up-treatment-protocol-2165559.html
Our 4 year experience using Cytosorb in pediatric cases
Our Four Years Experience of Hemoadsorption, Albumin and Heparin Treatment for Paediatric Sepsis: Let’s Give It a Chance in Multifactorial Pathological Conditions
https://bit.ly/3io6hTs
This article was just recently published in the Journal of Pediatrics. It is coming from the ICU and Pediatric ICU departments of some hospitals in Italy and is a historical report of the clinical decisions to use Cytosorb on 20 severely ill pediatric patients over the past four years. In the article they call out several patient cases that they considered a turning point to support using Cytosorb going forward as part of their therapeutic strategies. It should be noted that at the time these physicians were treating these patients there was a lack of data and procedure protocols and the device had not been registered and delivered for toddlers.
Because the use of Cytosorb for renal replacement therapy in the neonatal and pediatric setting the application of the same methods brought with it various challenges but significant technical difficulties, so these physcians refined and defined their experience patient after patient. There are unique technical challenges using Cytosorb for neonatal and pediatric extracorporeal mechanical support (ECMO) or neonatal cardiopulmonary by-pass surgery.
Some of the children highlighted in the article:
A 6 year old (21kg) who had a Fontan procedure done to repair their heart and encountered massive bleeding. The more the patient was bleeding the more the surgeon could not make correct sutures due to the amount of blood that was having to be transfused - the patient was dying for bleeding. They decided to apply a Cytosorb filter on a field blood recovery machine in a post reservoir bag position and started to give to patient Cytosorb filtered blood. In a few minutes the bleeding became normal and the procedure was completed and the the postoperative bleeding was very trivial.
Others highlighted in the article included a 4 year old with secondary hemofagocytic lymfohistiocytos as a consequence of infection (Streptococcus Pneumoniae). Vasoconstrictive drugs, fluid infusion and antibiotics had been tried but the patient had no response and was on the verge of imminent death due to MOF. Others included a 5 year old (29kg) with acute hemorrhagic encephalitis and cerebral edema on the verge of death and a 4 year old (16kg) kg who came in from the orthopedic unit due to Streptococcal Arthritis who was in very critical condition due to coma, respiratory insufficiency, septic shock and MOF, and cardiogenic shock. Cytosorb was used successfully as a rescue therapy in each of these cases.
I thought it was interesting that in some of the earlier cases, the physicans found themselves in a position to try and use Cytosorb to save the patient's life due to impending death with or without ethics committee approval and in some cases parental consent (remember the device is approved for sepsis in the EU and other applications but had very little documented off label use on patients weighing 40kg or less). However after each case they demonstrated they were able to submit a structured and clinically reliable protocol of Cytosorb to the Ethics Committee that later gave them permission to use Cytosorb in cases of imminent death.
These hospitals are now continuing to use Cytosorb on these pediatric patients in EVERY “Imminentia Mortis” clinical condition due to septic shock, sepsis, or MOF.
Cytosorb use to slow the aging process and progression of degenerative diseases?
The company just had a new patent published this month, for removing advanced glycation end products (AEG's) from a bodily fluids.
REDUCTION OF ADVANCED GLYCATION ENDPRODUCTS FROM BODILY FLUIDS
http://www.freepatentsonline.com/y2020/0188427.html
There is a lot to adsorb in this patent (no pun intended), but I will try and highlight a few things that stood out to me:
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- Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars in the body. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases.
- These degenerative diseases as well as aging are mainly based on a life-long accumulation of molecular damages within molecules, cells and tissues caused by these advanced glycation end products (AGEs).
- High levels of AGEs have been linked with the development of a variety of diseases including diabetes, heart disease, kidney failure, Alzheimer's and macular degeneration.
- There is a need for methods that treat, prevent or low the progression of diseases associated with AGEs.
- (This is where things get interesting) - One application is where blood or other bodily fluid is pumped out of the body, directly through a CytoSorb™ hemoperfusion cartridge where the beads remove AGEs, and the purified fluid is then pumped back into the body. "Other bodily fluids" include saliva, nasopharyngeal fluid, blood, plasma, serum, saliva, gastrointestinal fluid, bile, cerebrospinal fluid, pericardial, vaginal fluid, seminal fluid, prostatic fluid, peritoneal fluid, pleural fluid, urine, synovial fluid, interstitial fluid, intracellular fluid, extracellular fluid, lymph, mucus, or vitreous humor.
- The patent refers to other embodiments (implementations) which address how the sorbent may be formulated - for example, a powder, a tablet, a capsule, a solution, a slurry, an emulsion, a suppository, or in a food substance. The sorbent may be packaged in portable bottles, vials, blister packs, bags, pouches, or other container that allows for either single or multiple dosages. It also refers to other ways the sorbent can be delivered or administered besides extracorporeal - for example given orally, rectally, via a feeding tube, subcutaneous or transdermal delivery, or topical.
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If you are not familiar with AGE's, read this article when you have a chance, it explains everything you want to know about AGE's in layman terms:
"AGEs DamAGE Our Bodies"
http://longevityfacts.com/ages-damage-bodies-advanced-glycation-end-products/
Medical science has yet to invent a magic pill or potion that cleans a significant portion of AGEs from the body. There are drugs and enzymes being tested for use against AGEs but it's proving quite difficult as most drugs and enzymes will attempt to block the cell receptors that AGEs utilize to cause damage in the body. Although there is a lot of research with good prospects there is still to my limited research and knowledge no adequate drugs or therapies to get rid of advanced glycation end-products.
I would ask if there are those with a scientific or medical background to read this patent when they have time and also provide additional insights, because on the surface this looks to be an entirely new product that could come out of this and an entirely new market which is just mind boggling.