Monday, June 30, 2014

Clot-building nanoparticles raise survival rate following blast trauma Read more: Clot-building nanoparticles raise survival rate following blast trauma

A type of artificial platelet being developed to help natural blood platelets form clots faster offers promise for saving the lives of soldiers, as well as victims of car crashes and other severe trauma.
In preclinical tests led by a Case Western Reserve University researcher, the artificial platelets, called "hemostatic nanoparticles," when injected after blast trauma dramatically increased survival rates and showed no signs of interfering with healing or causing other complications weeks afterward.
"The nanoparticles have a huge impact on survival—not just in the short term, but in the long term," said Erin Lavik, an associate professor of biomedical engineering at Case Western Reserve. Other researchers had raised concerns that the foreign matter would interfere with healing, or form free-floating clots, but "we saw none of that."
The research, published in the Proceedings of the National Academy of Sciences this week ("Intravenously administered nanoparticles increase survival following blast trauma"), show the survival rate of mice models of blast trauma treated with the nanoparticles increased to 95, compared to 60 percent for those untreated.
Hemostatic Nanoparticles
Spherical hemostatic nanoparticles accumulate on a clot-stabilizing mesh of fibrin the body produces. (Image: Andrew Shoffstall)
Also, no unwanted side effects, such as accumulation of the nanoparticles, clot formation or aberrant healing, were found during examinations one ands three weeks after the injection.
Lavik worked with Margaret M. Lashof-Sullivan, Erin Shoffstall and Kristyn T. Atkins, of Case Western Reserve; Nickolas Keane and Cynthia Bir of Wayne State University and Pamela VandeVord of Virginia Tech.
Explosions account for 79 percent of combat-related injuries and are the leading cause of battlefield deaths, according to researchers at Veterans Affairs hospitals and the federally run Uniformed Services University of the Health Sciences.
The primary blast wave, flying shrapnel and being thrown to the ground cause the lungs, liver, kidneys and other organs to hemorrhage and bleed uncontrollably.
Such uncontrolled bleeding from collisions, blows and falls is also the leading cause of death among victims age 5 to 44 in the United States.
Natural blood platelets are the key ingredient to stopping bleeding, a process called hemostasis. The process works well for typical cuts and scrapes, but can be overwhelmed with serious injuries.
a schematic of hemostatic nanoparticles linking with blood platelets
This is a schematic of hemostatic nanoparticles linking with blood platelets. The nanoparticles significantly increased survival rate from blast trauma in preclinical testing. (Image: Erin Lavik)
Hospitals try to stem internal bleeding by giving trauma patients blood products or the hemophilia medicine called recombinant factor VIIa, but there isn't a good option for the battlefield or accident scenes. Recombinant factor VIIa must be refrigerated, costs up to tens of thousands of dollars per treatment and can cause clots in brain and spinal cord injuries, which are common from explosions.
Lavik's team has fine-tuned the nanoparticles to increase clotting efficiency. "They are incredibly simple… spheres with arms of peptides that react with activated blood platelets in damaged tissues to help clots form more quickly," she said.
The particles are made from short polymer chains already approved for other uses by the U.S. Food and Drug Administration. In earlier testing, rat models injected with the nanoparticles stopped bleeding faster than untreated models.
The dry particles remained viable after two weeks on a shelf. A medic in the field or an ambulance crew would add saline, shake and inject them, the researchers say.
Further research and testing are underway. Clinical trials on humans are likely at least five years out, Lavik said.

Tuesday, June 3, 2014

A device to control bleeding in brain surgery receives Phase 2 SBIR grant


EndomedixA medical device developer got a big boost in its efforts to develop a surgical sealant for brain surgery. Endomedix received a $1.49 million Phase 2 Small Business Innovation Research grant to help control bleeding for surgical procedures, according to a company statement. It received the grant from the National Institute of Neurological Disorders and Stroke.


The funding will go toward safety studies, in vivo performance studies and developing an applicator device. The sealant is a hydrogel that includes two processed biocompatible polysaccharides. They are simultaneously mixed and sprayed onto a surgical site.

Typically, a Phase 2 SBIR grant doesn’t exceed $1 million over a two-year period.

The market value for sealants and related devices is expected to top $4.2 billion in 2018. But some factors that could impact the size of the market include the efforts to limit expensive hospital admissions, shift procedures to outpatient settings and reduce rates of re-admissions.

Endomedix has won six SBIR Phase I grants totaling more than $1.1 million to advance its sealants program.

The Newark medical device company is based at the Enterprise Development Center incubator at the New Jersey Institute of Technology.

Sunday, May 18, 2014

Cohera Medical, Inc.® Files for CE Mark Approval for Sylys® Surgical Sealant

PITTSBURGHMay 15, 2014 /PRNewswire/ -- Cohera Medical, Inc.®, a leading innovator and developer of absorbable surgical adhesives and sealants, announced today that it has applied for CE Mark approval for Sylys® Surgical Sealant, the first synthetic sealant designed specifically to help reduce anastomotic leaks in gastrointestinal procedures.  CE Mark approval, expected by the end of 2014 based on this filing, will allow for marketing of the product in the European Union and other countries.
Sylys is applied during gastrointestinal procedures to help prevent the occurrence of anastomotic leaks – a serious complication that occurs in up to 23 percent of patients undergoing colorectal surgery. At least one-third of the post-surgical mortality after colorectal surgery is attributed to leaks, and survivors generally have protracted recoveries. The additional care required to manage this serious complication can cause up to a five-fold increase in patient management costs.
"Anastomotic leakage is the most devastating complication associated with intestinal resection, contributing to morbidity and mortality," said James McCormick, DO, FACS, FASCRS, Chief, Division of Colorectal Surgery, The Western Pennsylvania Hospital. "We have made tremendous strides in curtailing the risk associated with intestinal anastomosis, but we are always striving for further improvement and greater patient safety."
Sylys is designed to help reduce anastomotic leakage in intestinal procedures by providing additional support during the first few days of healing, when the development of leaks is most likely to occur.  The sealant is applied as a viscous fluid that cures rapidly to create a flexible, elastic seal over the anastomosis site.
"The preparation and filing of the CE Mark application for Sylys, a Class III implant technology, represents a significant milestone and achievement by all of the employees of Cohera Medical," said Chad A. Coberly, JD, Vice President of Clinical, Regulatory and Legal Affairs for Cohera Medical. "The submission signifies that we have completed the rigorous clinical and pre-clinical testing, quality, and performance requirements of the EU authorities, and we look forward to working with our notified body during the approval process."
The market for Sylys is significant, with several hundred thousand procedures a year worldwide representing a multi-billion dollar opportunity. Due to the unmet clinical need, Sylys would represent a breakthrough in this market that will lead to improved patient outcomes as well as reduced patient management costs for healthcare providers.
"Submitting the Sylys CE Mark application represents a significant milestone towards the commercialization of our second product and demonstrates the commitment we have to our future customers, partners, and investors," said Patrick Daly, Cohera Medical president and CEO. "We look forward to making Sylys available to surgeons and patients throughout the world."

Monday, May 5, 2014

Z-Medica Bolsters Hemostatic Product Line with Acquisition of Novacol®

WALLINGFORD, CONN. — Z-Medica, a leading developer and marketer of hemostatic agents, today announced that they have signed a definitive agreement with TAUREON, headquartered in The Netherlands, to acquire Novacol®, a Class III resorbable hemostatic product.

Novacol is currently sold in Europe and South Korea. Z-Medica will continue to support that marketing strategy while making plans to expand the product offering into other countries.

“Given our QuikClot portfolio of hemostatic dressings, it was a natural fit for us to augment both our product line and our international presence with Novacol,” said Z-Medica’s President and CEO Stephen J. Fanning. “Our current products are gauze-based and non-resorbable. Acquiring Novacol, which is a resorbable hemostat, is the first step towards expanding the Z-Medica portfolio and providing a wider range of innovative, safe, and effective products to the broader healthcare market.”

Used primarily in surgeries, Novacol is comprised of 100% high-quality, purified, natural long and short collagen fiber, which is resorbed by the body. The product is available as the soft, pliable Novacol® Pad, and Novacol® Fibrillar for use in cavities and irregular surfaces.

“Novacol is an effective product that will benefit from Z-Medica’s global distribution network,” said TAUREON CEO Dick van Kalkeren. “Z-Medica’s experience with QuikClot and their reputation as a leader in the hemostatic market ensures that Novacol will be able to compete favorably in the market. The transfer of Novacol also enables TAUREON to strengthen our focus in Europe on plastic and orthopedic surgery, human tissue and advanced wound care.”

Wednesday, April 23, 2014

The Medicines Company Adds Novel, Approved, Surgical Sealant to Its Surgical Hemostasis Portfolio Acquires Tenaxis Medical, Inc.

PARSIPPANY, NJ and MOUNTAIN VIEW, CA -- (Marketwired) -- 04/23/14 -- The Medicines Company (NASDAQ: MDCO) and Tenaxis Medical, Inc. (Tenaxis) today announced an agreement for The Medicines Company to acquire Tenaxis. Tenaxis's sole product, which mechanically seals both human tissue and artificial grafts is approved, but not launched in the US -- having received US PMA approval from the FDA in March 2013 as a vascular sealant. The product is also approved with a European CE Mark as a surgical sealant applicable to cardiovascular, general, urological, and thoracic surgery. The addition of the Tenaxis product adds another solution for surgical bleeding to The Medicines Company's portfolio which also includes the marketed product, RecoThrom (aqueous, recombinant human Thrombin) and the investigational product, Fibrocaps (a dry powder formulation of fibrinogen and thrombin being developed to aid in hemostasis during surgery) which has completed phase III trials and is under FDA and EMA review.

Under the terms of the agreement, The Medicines Company will pay $58 million upfront on closing of the deal. The Medicines Company will also pay milestone payments of up to $112 million contingent upon achieving certain commercial and -- in pursuit of even broader indications -- regulatory approval milestones. The transaction is subject to the satisfaction of customary closing conditions.

"We continue to execute our strategy for growth, building our presence in surgery and perioperative care," said Clive Meanwell, Chairman and Chief Executive Officer of The Medicines Company.

Adam Sharkawy, Senior Vice President and Global Innovation Group Leader for Surgery and Perioperative Care added, "A robust portfolio of solutions for intra-operative bleeding is expected to drive growth for us in this sector of hospital medicine. This acquisition will allow us to leverage and build our activities in surgery centers at leading US and European hospitals. In the US, we expect to deploy approximately 100 of our current engagement managers across these surgical product offerings."

In a pivotal trial in vascular surgery, the Tenaxis sealant was effective when used as prophylactic treatment on native vessels and grafts, reducing the incidence of bleeding within the first minute after removal of vascular clamps. The Tenaxis sealant was compared to Gelfoam Plus, a topical hemostat containing a low concentration of thrombin (125 Units/mL), in the clinical trial used to support licensure (N=217; 1:1 randomization). The Tenaxis surgical sealant was shown to be superior to Gelfoam Plus based on a statistically significantly lower incidence of suture hole bleeding at the time of clamp release (60.5% vs. 39.6% of anastomotic sites at Time 0; p = 0.0001); the 20% difference at the time of clamp release persisted at 10 minutes (82% vs. 72%). Superiority was demonstrated in several types of surgical procedures (extremity bypass, hemodialysis access grafting, and other vascular procedures).

"We are excited to be involved in a transaction with The Medicines Company, which will allow more patients to have access to this beneficial technology," Ronald Dieck, President and CEO of Tenaxis commented. "We are proud of the surgical sealant technologies that we have developed and their impact on the wellbeing of patients. The Medicines Company is clearly committed to the area of intraoperative hemostasis and we look forward to working as a team to innovate in this area of medicine."

The Boards of Directors of both companies have unanimously approved the agreement.

Gibbons P.C. served as legal advisor for the transaction for The Medicines Company. Leerink Swann & Co. served as financial advisor and Wilson Sonsini Goodrich & Rosati, PC served as legal advisor for the transaction for Tenaxis Medical, Inc.

Conference Call Information

There will be a conference call with The Medicines Company management today at 8:30 a.m. Eastern Time to discuss the Tenaxis acquisition, first quarter 2014 financial results, operational developments, and outlook. The conference call will be available via phone and webcast. The webcast can be accessed at www.themedicinescompany.com.

Domestic Dial In: +1 (877) 359-9508 
International Dial In: +1 (224) 357-2393 
Passcode for both dial in numbers: 27882505

Replay is available from 11:30 a.m. Eastern Time following the conference call through May 7, 2014. To hear a replay of the call dial +1 855 859-2056 (domestic) and +1 404 537-3406 (international). Passcode for both dial in numbers is 27882505.

Saturday, April 5, 2014

FDA Accepts Biologic License Application for Fibrocaps Hemostatic Agent

The Medicines Company has announced that the U.S. Food and Drug Administration (FDA) has accepted the filing of a biologic license application (BLA) for the investigational hemostatic agent Fibrocaps, a dry powder formulation of fibrinogen and thrombin being developed to aid in hemostasis during surgery, where control of mild or moderate bleeding by conventional means is ineffective or impractical. The FDA action date (PDUFA date) for Fibrocaps is January 31, 2015. 

In August 2013, The Medicines Company announced that the Phase III trial, FINISH-3, which studied a total of 719 patients across 54 sites in the U.S. and Western Europe, met all of its primary and secondary hemostasis efficacy endpoints in each of four distinct populations: (1) spinal surgery; (2) hepatic resection; (3) soft tissue dissection; and (4) vascular surgery. 

"We believe Fibrocaps has the potential to become an important hemostatic product -- complementary to Recothrom® Thrombin, topical (Recombinant) -- which will allow us to continue to serve leading US hospitals, leveraging our existing operations. Our previously announced EMA filing also suggests that Fibrocaps can be our first hemostat product in the European market," said Adam Sharkawy, PhD, Senior Vice President, and Surgery and Perioperative Care Global Innovation Group Leader at The Medicines Company. 

"With the acceptance of the Fibrocaps BLA we now have 6 new molecular entity regulatory submissions under review at the FDA and the EMA," said Clive Meanwell, MD, PhD, Chairman and Chief Executive Officer of The Medicines Company. "These applications span our three areas of focus in leading hospitals, namely: acute cardiovascular care, surgery and perioperative care, and serious infectious disease care. Each is designed to contribute to our purpose which is to save lives, alleviate suffering, and contribute to the economics of healthcare by focusing on the needs of leading hospitals worldwide."

Sunday, March 23, 2014

Drug companies developing longer-acting clotting agents for hemophiliacs

Several drug companies, such as Biogen Idec and Novo Nordisk, are developing new, longer-acting versions of the blood clotting factors used by people with hemophilia. Patients with severe forms of the disease need regular infusions, lasting 30 minutes or more, of relatively short acting and very expensive clotting factors.

The new longer-lasting hemophilia B products can be given every 10 days or two weeks, offering significant advantages for patients, especially young children, who now need infusions every two or three days.

Hemophilia is hereditary, passed from parent to child through genes. People with hemophilia have little or no clotting factor. Hemophilia A and Hemophilia B have different clotting factors that are low or missing, but both can experience spontaneous bleeding, as well as severe bleeding following injuries or surgery.

Worldwide, about one in 5,000 men is born with hemophilia A and one in 25,000 men is born with hemophilia B each year. Since the gene is carried on the X chromosome, hemophilia is almost entirely a disease of men. Women can pass the gene to their offspring. Hemophilia has often been called the “Royal Disease” since it was carried by Britain’s Queen Victoria and affected many of the ruling families of Europe. Blood factor concentrates were not developed until the mid-20th century, and up until that time people with hemophilia had a life expectancy of less than 30 years.

The U.S. Food and Drug Administration is due to decide by mid-year whether to approve a new long-lasting hemophilia B clotting factor from Biogen Idec. Novo Nordisk expects to file next year for regulatory approval of its long-acting hemophilia B drug.

Some industry experts say these and other new treatments could help drive down the price of existing hemophilia products, which can total $300,000 or more a year for a single patient.

Saturday, March 22, 2014

Mercy adopts new blood cell transfusion guidelines

SIOUX CITY | Mercy Medical Center -- Sioux City has stepped up efforts to conserve red blood cells.
All hospitals in the Trinity Health network have applied the new national recommendations developed by The Joint Commission and the American Medical Association -- convened Physician Consortium of Performance Improvement that advise adopting a "more restrictive" practice of red blood cell transfusion to produce better patient outcomes.
"We want to give just what is necessary, one unit at a time," said Dr. Gregg Galloway, a pathologist and vice chair of the Infectious Disease Committee at Mercy. "Give him a unit of blood. It will make him feel better -- that's the old paradigm. We don't believe it anymore."
Mercy has always had guidelines in place instructing staff when to give red blood cell transfusions, but Galloway said those rules have significantly changed and are "more restrictive" than they used to be.
"We're doing it because we do believe it is better quality patient care at all health care institutions and because of the cost of the resources," he said.
The new guidelines were released following a September 2012 national summit that convened representatives from 112 professional organizations and associations in effort to curb overuse of five medical treatments. Transfusion of red blood cells in hospitals was one of them.
A decade of studies, according to Galloway, found that when "more restrictive" red blood cell transfusion practices were used, hospitalized patients had lower mortality rates, fewer complications from infectious diseases, less breathing problems and cardiac events, as well as a reduced chance of developing acute respiratory distress syndrome -- a life-threatening lung condition that prevents enough oxygen from getting to the lungs and into the blood.
Galloway said hospital staff give patients red blood cell transfusions based on their hemoglobin (a protein in red blood cells that carries oxygen) and hermatocrit values (percentage of red blood cells found in whole blood). When their hemoglobin value dropped below 10 grams per deciliter (G/dL), the patients received a transfusion. The "more restrictive" guidelines, he said, don't recommend transfusion until hemoglobin values fall between 7 and 8 G/dL.
"Big difference. You're going to use less red cell and units in the hospital," he said. "We predict that overall we'll have a 15 to 20 percent drop over the next year and a half to two years in our red cells that we'll use in our hospital setting."
Once blood is collected at a donation center, it's processed, placed in a refrigerator and stored. Chemical changes, he said, occur in the hemoglobin, and red blood cells lose their malleability.
"Those red blood cells start to change," he said. "They are no longer like the normal red blood cells you and I have floating around in our body. Banked blood is a tissue transplant. Those are somebody else's red cells."
In addition to the new guidelines, Galloway said, improvements in surgical techniques that reduce the need for red blood cell transfusions in the operating room are also contributing to the downward trend.
Surgeons are encouraged to salvage patients' blood in the operating room, a practice that was once reserved for open heart surgery. Now it's being used in trauma, abdominal aneurism and orthopedic surgeries.
"We're trying to save the patient's own blood. We re-process it in the OR and we give it back to them," Galloway said. "We also have new hemostatic medications that we can give patients that keep them from bleeding as much in OR."
Large hospitals, he said, now have blood management programs that staff nurses who review a patient's clinical situation alongside the guidelines. Some patients seeking elective surgery, he said, may have to wait longer to get into the operating room if they lack enough healthy red blood cells.

Adhesion Incidence and Severity Vary by Surgical Procedure

Experts estimate approximately 93% of patients who have undergone laparoscopic surgery develop abnormal fibroid bands that bind organ surfaces to the abdominal wall after a second surgery. Many adhesions are asymptomatic, but in some patients, they can cause pain, small bowel obstruction and other postoperative issues, as well as increase cost and complicate surgical suite workload. As surgeons underestimate the rate of adhesion development given that up to 93% of consent forms don’t address them, the March 2014 issue of Surgery Today contained a systematic review estimating the formation rate, distribution, and severity of postoperative adhesions in abdominal surgery patients.
After reviewing 25 studies published between January 1990 and July 2011, the authors determined the weighted mean formation rate of adhesions after abdominal surgery was 54%. However, different types of surgeries and procedures had different adhesion statistics. Among patients who had gastrointestinal (GI) surgery, 66% developed adhesions. In patients who had gynecologic and urologic surgeries, the rates were 51% and 22%, respectively.
Since those rates were lower than the numbers reported a few decades ago, the authors suggested current practices such as minimizing peritoneal foreign body exposure, careful tissue handling, meticulous hemostasis, specific closure of the peritoneum in caesarean sections, and modern surgical techniques have helped reduce the rate of adhesion.
The authors reported laparoscopic surgery reduced the adhesion formation rate by 25% and also decreased the adhesion severity score for Gl surgery.  They concluded heightening awareness of adhesions is needed to shed light on the complication’s etiology. With better understanding of how and why adhesions form, researchers will be able to develop novel therapeutic approaches, the authors said. They also suggested the potential for adhesions should be addressed clearly in consent forms.

Friday, February 7, 2014

Popular Blood-thinner Manufacturer Didn’t Want Internal Research Made Public

Boehringer Ingelheim, the manufacturer of the blood-thinning drug Pradaxa, was concerned that releasing the results of an internal research paper on the drug would damage drug sales, records recently made public show. The company was so worried about the results of the study that some employees pressured the author to revise it, and the company recommended it be thrown out, according to a recent report by the New York Times.

Records recently made public by a federal judge in Illinois presiding over thousands of lawsuits against the maker of Pradaxa, including emails, internal memos, and presentations, centered on the research project and whether it would be damaging to Pradaxa’s main selling point: that users of the drug aren’t required to undergo regular blood work while taking Pradaxa.

Pradaxa (dabigatran) was approved in 2010 as an alternative to an existing anti-clotting drug, warfarin. Both are anticoagulants used to prevent and treat blood clots and reduce the risk of stroke, but Boehringer Ingelheim marketed its drug as less of a nuisance than warfarin, which requires frequent blood tests and careful monitoring.

Unfortunately, Pradaxa has been linked to more than 1,000 deaths in the United States. Since 2010, an unprecedented number of adverse events related to the drug have been reported to the FDA. Experts have also questioned the reliability of an FDA study affirming the safety of Pradaxa.

Pradaxa has claimed superiority to warfarin. However, documents prepared by the FDA clearly state that “It is important… not to provide dabigatran with a superiority claim to warfarin, because it would imply that even those well-treated with warfarin should be switched to dabigatran. Clearly, that is not the case.”

Furthermore, a research paper written by Paul. A. Reilly, a clinical program director with Boehringer Ingelheim indicates that patients could benefit from having their blood monitored while taking Pradaxa. Reilly states that some patients absorb too little of the drug, rendering it ineffective, while some absorb so much that their risk for bleeding increases.

According to the New York Times, after Reilly’s paper was circulated within the company, Dr. Jutta Heinrich-Nols, a company supervisor, sent an email stating that she couldn’t believe the company was planning to publish Reilly’s work. She warned that publishing his results could make it “extremely difficult” for the company to maintain its claims that patients taking Pradaxa do not need regular blood tests.

Heinrich-Nols also noted that Reilly’s research could “undermine” the company’s efforts to compete with other new anticoagulants like Xarelto and Eliquis. The marketing of Pradaxa is yet another example of the dangers that consumers face when safety information is regulated by pharmaceutical companies primarily concerned with profit.

Boehringer Ingelheim issued a statement saying that the recently-released documents “represent small fragments of the robust discussion and debate that is a vital component in all scientific inquiry and in the research and development of any important medication such as Pradaxa.”

Unlike warfarin, Pradaxa has no antidote to reverse its blood-thinning effects. Despite issues with the FDA’s approach to approving the drug, as well as numerous patient bleeding deaths and adverse event reports, Pradaxa remains on the market as a safe drug.