Agree - Russia has 143,000,000 people and presents a potentially lucrative market for the company. The addressable market is bigger than France, Poland, Sweden, Denmark, Norway and Finland combined (which is Fresenius territory). However my understanding from what I have read is that registration is challenging. Unlike most countries, Russia still relies on in-country product testing to grant approval for medical devices, and this testing must be completed regardless of whether the device already has US 510(k) clearance or European CE marking. The Russian regulatory environment remained in a state of flux the last 4 years and there have been even more changes and as of today even some areas of the regulatory process remain undefined.
On the positive side of things however is that as a consequence of enforcing changes in the registration rules around the middle of 2014, and having had some years of experience with the new regulatory system, the common trend for 2015 was that medical device registration processes remained challenging, but became quicker and more predictable compared to previous years. According to statistics announced in December by the Roszdravnadzor (Russian medical device regulator), the average time of registration for a medical device in 2015, including clinical evaluation or clinical trials, was 8-9 months for both Russian and foreign manufacturers in 2015.
I think the company probably submitted the registration at a time when the rules were still in flux, thus the lengthy approval time. The latest official status from the company I could find was from the prospectus filed on 11/05/2015: "CytoSorb and its distribution partner in Russia have submitted all requested documentation for registration, and await a response from the Russian authorities."
This new trial is being conducted at University Medical Centre, in Ljubljana, Slovenia which is internationally renowned for leading innovation in cardiovascular surgery. They are a site also for the first clinical implants of CARMAT bioprosthetic artificial heart - the worlds most advanced bioprosthetic artificial heart. Their transplant activity has been steadily growing year on year resulting in an extensive waiting list. They are the largest hospital centre in Slovenia with over 2000 beds and 7000 employees, and perform over 100,000 in-patient admissions per year, making it one of the largest hospitals centers in Central Europe.
Excerpt from the study purpose: "The balance of pro-inflammatory and anti-inflammatory mediators determines the inflammatory response and the clinical outcome. Accordingly, great efforts have been focused on therapeutic interventions aimed at reducing the inflammatory reactions during CPB, including pharmacologic strategies and modification of surgical techniques or mechanical devices. Such therapies may provide improvements in patient outcome after open heart operations. Among pharmacologic strategies is the prophylaxis with corticosteroids, which have been used during open heart surgery for more than 30 years. Many studies, both experimental and clinical, failed to produce evidence in favor of steroid treatment. As far as medical devices are concerned, the use of extracorporeal cytokine filter CytoSorb looks promising in cardiac surgery. It was recently approved by European Medicines Agency as an active treatment to fight cytokine storm."
Yes, Q4 included initial orders from Fresenius. From the Jan 11th release/shareholder letter: "Healthy growth from distributors and partners also contributed to the record quarter, including new product orders from Fresenius Medical Care, the world's largest dialysis company and our partner in 6 countries in Europe, and continued orders from Biocon, the largest biotechnology company in India." Still pending is the anticipated tender order from Saudi Arabia which according to the company should be fairly substantial.
Things began to pickup after they brought on Steve Sisk as Director-Clinical Operations to oversee the day-to-day operations of the trial around the middle of last year. He knows a thing or two about running CRO management and negotiations, clinical study planning and execution and directing large cross-functional development teams, having been previously Senior Director of Clinical Operations at Medtronic. His has also performed similar functions priot to that at Nordisk, Nektar Therapeutics and Applied Biosystems.
Columbia University which is also recruiting, trial location is at NewYork-Presbyterian which was ranked #1 in New York and #3 in the nation for cardiac surgery specialization by US News and World Report. They are recognized by Castle Connolly for having the most top heart specialists in the nation. Dr. Michael Argenziano the lead investigator.
Department of Surgery
Division of Cardiac, Vascular and Thoracic Surgery
Appointments: (212) 305-5888
Contact: Lyn Goldsmith, MA, RN, BSN, CCRC
Phone: (212) 342-0261
BayState Medical in Springfield, MA is one of the sites currently recruiting patients for REFRESH. More than 80% of all cardiac surgeries in western Massachusetts are performed at Baystate Medical Center. It is among the top three highest-volume medical centers in the entire state for coronary surgery and coronary angioplasty. The hospital has participated in more than 100 cardiology clinical trials. Dr. Richard Engelman is a thoracic and cardiac surgeon with 52 years in practice is the lead researcher. .
RB Number: 774507
Condition/Disease: Surgery, Heart
Lead Researcher: Richard Engelman, MD
Location: Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199
Purpose: The purpose of this study is to evaluate the safety and performance of the CytoSorb®device to reduce plasma free hemoglobin when used intraoperatively with cardiopulmonary bypass (CPB) in subjects undergoing cardiac surgery.
Eligibility: Subjects must be undergoing cardiac surgery requiring CPB with ananticipated length of CPB greater than or equal to 3 hours.
Contact Name: Barbara Burkott
Hope pears got out before the dumping.
pearsby09 • Oct 2, 2015 11:02 AM
"Obviously, the FDA is still waiting for additional closure on as much data as possible prior to PDUFA, so why not other sources. Before all you Brain Washed pumpers get your undies in a bunch..I agree the data presented this week was extraordinary and my husband and I added at 36.44. We will have our day, but unfortunately the stock is still not in the national lime light and remains under the media radar. Which is great for further accumulation as dry powder becomes available. Your...Beloved....Pearsby"
pearsby09 • Oct 4, 2015 2:55 PM Flag
BTW, SRPT is the stock I hope to retire on and also hope the DMD families get a viable treatment. If the FDA denies, I will be toast. Your, Too Speculative and Risky...Beloved...Pearsby
This could mean one of two things - either the original partner backed out of the negotiations after the market evaluation or other potential partners have also approached them with potential deals which they are evaluating.
Luv, you are correct. When I read through the IFU document in the footer I see now in fine print it is dated November 2012. Updated product literature and accompanying documentation from Techno Orbits would be included.
After conducting a fairly extensive set of searches I found the product registration information for Cytosorb on the Saudi Food and Drug Authority (SFDA) web site. I have however been unable to find information concerning the tender order or related shipment(s) due to the fact that that information sits behind sites that either require registration or a paid service.
The MDMA listing # is MM04282SFDAA001 and the product authorization number is MDMA15060183. This information along with the product's detailed instructions for use along with the registration certificate can be found at the mdma.sfda.gov web site. The marketing authorization was issued on June 17, 2015 and expires September 1, 2016.
The instructions for use which include all the details for precautions, limitations, patient prep/initiation/and post treatment steps. Below are excerpts of intended use and indications paragraphs from the IFU documentation.
1.1 Intended Use
The CytoSorb Device (CytoSorb) is a non-pyrogenic, sterile, single-use device
designed to remove cytokines. CytoSorb contains adsorbent polymer beads that
adsorb cytokines as blood passes through the device. CytoSorb is placed in a
blood pump circuit.
CytoSorb is indicated for use in conditions where excessive cytokine levels exist.
Results from current studies suggest that CytoSorb may be used 6 hours per
day, for up to 7 consecutive days.
Acceptable Blood Flow Rate: 200-400 mL/min
Optimum Blood Flow Rate: 250-400 mL /min
If I am able to locate information concerning the tender order I will post that as an addendum here.
As was brought to light in a recent post by ping, the company has responded to federal contract opportunity W81XWH16T0038 for surgical appliance and supplies manufacturing at U.S. Army Medical Research Acquisition Activity, which was due Jan 4, 2016. The U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) Bacteriology Division is in the process of purchasing custom cytokine filters from CytoSorbents, Inc. for use in a funded project to develop new biodefense countermeasures. The CytoSorb filters are required to test the effect the filters have as a treatment against SEB toxin exposure, anthrax and plague in non-human primate models. The filters will be developed to match USAMRIID’s animal model and bacterial targets.
This looks to be part of the advanced development efforts to support the Department of Defense’s (DoD) medical pharmaceutical and diagnostic requirements which is being led by the Joint Project Manager for Medical Countermeasure Systems (JPM-MCS). A Consortium OTA (Other Transaction Agreement) business model has been developed which is a new binding contractual instrument to work with DOD to develop FDA Licensed Chemical, Biological, Radiological, and Nuclear (CBRN) Medical Countermeasures. The Consortium OTA will have an initial $10 billion ceiling and a 20-year performance period. A couple of points of focus that stood out as pertinent to Cytosorbents included: Form robust long term partnerships with qualified providers, create a rapid response capability to emergent threats and requirements, place technically acceptable proposals placed in the “basket” awaiting funding and provide unity of effort among defense organizations from discovery through FDA Approval.
With the company's existing in-roads through the DARPA and US Army work to date in the areas of sepsis and trauma, this could prove to be another inroad into defense department work as well as providing the ability to work across traditional boundaries (e.g FDA).
No, I think the cat is out of the bag now - that pearbrain is married to iowajake. These are iowajake's additional aliases: angelajerkel and dr_1owenstein. She said her husband has been on this board for years so that would probably account for this, as he's been posting under these three aliases for as long as you and I have been on this board. Yahoo used to have a way with its Groups functionality a way you can tell which aliases are linked to the same email address so I know for a fact that these are his three aliases. We know at least one of pear's other aliases 'krichard' from one of lovboats old posts. I think she must have come in from her volleyball match and forgot her husband was still logged in under his alias. Oh well, I guess her SRPT has not done as well as she hoped so she's taking a last minute flyer by 'jumping back in'.
"the Company concluded there would be no significant time or cost advantage associated with pursuing the EAP designation for CytoSorb for the treatment of sepsis, and that a traditional IDE trial followed by a PMA application as originally planned by the Company is the preferable route to seek approval of CytoSorb for treatment of sepsis that would potentially also not require a post-market efficacy study required by the EAP."
In reading back through some of the case studies, one that was intriguing was the first reported use of CytoSorb in the setting of pruritus which an unpleasant skin sensation or itching that frequently provokes scratching that can be associated with a number of disorders, including dry skin, skin disease, etc.
The case study reported from the Department of Anaesthesiology, Klinikum Rechts der Isar Technical University of Munich, was that of a 44 year old male patient with pruritus and severe sleep disturbances. Prior medical conditions included primary sclerosing cholangitis with subsequent LTX and reLTX one month later due to primary graft failure. Efforts to treat the pruritus using drugs were unsuccessful. Therefore two treatment attempts were made using CytoSorb. Application of the filter resulted in a significant decrease of bilirubin and bile acid plasma levels, and considerable patient benefit as assessed by a decrease of VAS to 0 and an accompanying improvement of the patients’ complaints. The treatments were made using a Multifiltrate® dialysis machine (Fresenius).
The global pruritus therapeutics market is expected to reach USD 16.38 Billion by 2025, according to a new study by Grand View Research, Inc.
So what's changed in the last 8 months since your last positive opine in May? - I wouldn't exactly say that is someone who has a long term view or a value investor.
mikesmith999945 • May 6, 2015 1:47 PM Flag
2users liked this postsusers disliked this posts0Reply
I fully agree with you, patience is a virtue.
Dr. Chan and his crew are doing an excellent job, we just have to trust them.
At the moment we are still under the radar, but it's a matter of time b4 the media picks it up.
USAMRIID was mentioned last year (Aug 2014) in one of the company's presentations as it related to the Ebola outbreak as one of the agencies along with the CDC, WHO and FDA whom the company reached out to. In January of this year the ISAMRIID, Harvard University, and Massachusetts Institute of Technology (MIT ) studied genetic changes in the Ebola virus (EBOV ) circulating in West Africa and concluded that there was a "genetic drift" (mutation) in the Ebola virus that must be considered when developing potential therapeutics, in order to ensure that changes in the Ebola virus over time do not render those treatments ineffective". I wonder if this is in response to that or other purposes.
Interesting development, thanks ping. USAMRIID has served as the Department of Defense's (DoD) lead laboratory for medical biological defense research. "While our core mission is to protect the warfighter from biological threats, we also investigate disease outbreaks and threats to public health. Research conducted at USAMRIID leads to medical solutions—therapeutics, vaccines, diagnostics, and information—that benefit both military personnel and civilians." Also "We continue to develop new and improved vaccines, working with the Food and Drug Administration (FDA) to move medical products forward using the "animal rule. Under this rule, specifically designed for biodefense vaccines and drugs, products can be considered for FDA licensure using data from animal studies in cases where human clinical trials cannot be conducted."
Last year might be used as an indicator as to the timing of when the company might try to conclude any negotiations and announce a strategic partnership with this global cardiac surgery company. The initial agreement was signed in November 2014 and the Fresenius partnership was announced in December 2014 just before the conclusion of the fiscal year. On top of that the officers incentive compensation plan for 2015 has built in provisions based on the achievement of one or more new major strategic partnerships in the fiscal year. In fact 25% of the incentive compensation is tied to both this as well as "demonstration of reasonable progress in the U.S. regulatory approval" (EAP).
Stock options are performance based and vest upon achievement of the following milestones:
(a) 45% vest upon achieving 2015 budgeted revenues and not exceeding budgeted operating expenses;
(b) 30% vest upon achievement of multiple clinical trial objectives in calendar year 2015, as determined in the discretion of the Board of Directors;
(c) 15% vest upon demonstration of reasonable progress in the U.S. regulatory approval of one of the Company’s products, as determined in the discretion of the Board of Directors; and
(d) 10% vest upon achievement of one or more new major strategic partnerships, as determined in the discretion of the Board of Directors.
And just to state the obvious, Dr. Scheier was hired AFTER this agreement was signed, so the timing seemed interesting after going back and looking at this. Like ping I believe that all roads point to Sorin.
Continued from the Scheier April press release:
"Dr. Scheier brings to CytoSorbents a well-established key opinion leader network in critical care and cardiac surgery, and a wealth of experience in clinical trial design and management of both sponsor and investigator-initiated medical device clinical studies, both before and after approval. In addition, as a veteran of clinical operations and industry, he brings a diverse set of skills and expertise in regulatory affairs, medical advisory board management, product safety monitoring, sales and marketing training and support, reimbursement, project management, and the identification and evaluation of promising future technologies. "
Dr. Joerg Scheier remarked, "Since starting with CytoSorbents, I have already spoken to many physicians who are seeing CytoSorb® treatment work first-hand in very difficult cases and can see their energy and enthusiasm for the therapy. My goal at CytoSorbents is to foster and grow the medical and health economics data around CytoSorb® therapy and make it a routine first-line choice by physicians to treat their patients. I truly believe that CytoSorb® has the potential to re-define critical care as a novel therapy for life-threatening conditions and holds great promise for use during and after cardiac surgery as well. The potential of CytoSorbents' portfolio of technologies fascinates me and I am excited to apply my experience, both in clinical trial management and in the care of critically-ill patients, to help bring these technologies to patients in need."